Head and neck cancer (HNC) currently affects approximately 11 200 people in the UK, with an increasing proportion known to be caused by the human papillomavirus (HPV). We undertook a systematic review of studies measuring the psychosocial impact of HPV-related HNC and also studies measuring knowledge about the link between HPV and HNC among different populations. Searches were conducted on MEDLINE, Embase, PsycINFO, CINAHL Plus and Web of Science, with reference and forward citation searches also carried out on included studies. Studies were selected if they (i) were original peer-reviewed research , (ii) mentioned HPV and HNC, (iii) measured an aspect of the psychosocial impact of the diagnosis of HPV-related HNC as the dependent variable and/or (iv) measured knowledge of the association between HPV and HNC. In total, 51 papers met the inclusion criteria; 10 measuring psychosocial aspects and 41 measuring knowledge of the link between HPV and HNC. Quality of life in those with HPV-positive HNC was found to be higher, lower or equivalent to those with HPV-negative HNC. Longitudinal studies found quality of life in patients was at its lowest 2–3 months after diagnosis and some studies found quality of life almost returned to baseline levels after 12 months. Knowledge of the link between HPV and HNC was measured among different populations, with the lowest knowledge in the general population and highest in medical and dental professionals. Due to the limited studies carried out with patients measuring the psychosocial impact of a diagnosis of HPV-positive HNC, future work is needed with the partners of HPV-positive HNC patients and health professionals caring for these patients. The limited knowledge of the association between HPV and HNC among the general population also indicates the need for research to explore the information that these populations are receiving. We searched MEDLINE, Embase, PsycINFO, CINAHL Plus and Web of Science using relevant search terms for the overview. There were no language or date restrictions applied to the search. All references were reviewed against the inclusion and exclusion criteria. Additional relevant papers were found through searching the reference lists of included studies and carrying out forward citation searches on included studies.Head and neck cancer (HNC) affects about 11 200 people in the UK each year It is now clear that an increasing proportion of HNC cases are caused by the human papillomavirus (HPV) We know from the cervical cancer literature that the sexually transmitted nature of HPV can lead to additional psychological challenges to those associated with the cancer itself. Women have felt stigma, anxiety, concern about their relationships and worry about disclosure of their test results to others, following a diagnosis of HPV in the context of cervical screening Research has started to explore what the public know about HPV and HNC and how an HPV diagnosis affects patients. Knowledge of HPV appears to have increased following the introduction of the HPV vaccination, which is now offered to adolescents in most developed countries (i)What is the psychological impact of an HPV diagnosis in the context of HNC?(ii)What is known about HPV-related HNC in different population groups?This review is timely in drawing together findings from the emerging literature and identifying priorities for a behavioural science research agenda in this field. The evidence from both the cervical cancer and HNC literature suggests that there may be greater psychological distress in these patients due to the combination of both a diagnosis of cancer and of HPV. The review aims to answer two questions:opensigle.inist.fr). Results of the literature search were downloaded into Endnote with duplicate articles removed.Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for this systematic review Studies were included if they (i) were original peer-reviewed research , (ii) mentioned HPV and HNC, (iii) measured an aspect of the psychosocial impact of the diagnosis of HPV-related HNC as the dependent variable and/or (iv) measured knowledge of the association between HPV and HNC. Studies were excluded if they were not written in English, did not report original research or were conference abstracts.Article titles were screened by two authors  and were excluded if they were not written in the English language or were clearly irrelevant to the review. Two members of the review team  then screened the abstracts of the remaining articles, looking more specifically for articles mentioning HPV. Authors of conference abstracts that appeared to meet the eligibility criteria were contacted to request a copy of the full paper if it was available. Those not submitted or published in peer-review journals were excluded and one author did not reply after multiple attempts to contact them, so this paper was also excluded. Disagreements were resolved by discussion and reasons for inclusion/exclusion were noted. Articles that appeared to meet the inclusion criteria based on the title and abstract screen were obtained for full-text review . Copies A full-text eligibility review was conducted by two members of the review team  with reasons for exclusion recorded. Reasons for excluding studies included the article not containing any original data relevant to our eligibility criteria, not mentioning HPV or not measuring our outcomes of interest as dependent variables. Forward citation searches were conducted for all papers obtained for full-text review and included those published up to August 2015. Eligibility of articles found through forward citation and reference searching was confirmed by a second screener (LM). A summary of the data from all full-text articles was extracted , Table 2Data from all included articles were recorded using a data extraction form. The results from articles measuring psychosocial outcomes and knowledge are reported descriptively with comparisons drawn where appropriate. Qualitative findings are described separately.The initial search returned 782 articles, which was reduced to 491 after the removal of duplicates; 448 were excluded on the basis of their title, leaving 43 abstracts to be reviewed. Once the articles had been screened by title and abstract, 25 were obtained for full-text review. An additional 37 articles were included after searching the reference lists, relevant review papers found through the search and searching forward citations of those already obtained for full-text review. Eleven articles were excluded during full-text review, leaving 51 papers included in the final analysis. Ten of the studies measured psychosocial outcomes The psychosocial impact of HPV-related HNC was measured in patients Quality of life was the main outcome measure used in seven studies and was measured using a number of different tools. Six of the studies measuring quality of life used at least one HNC-specific measure . Two stuThree studies did not include a comparison between HPV-positive patients and HPV-negative patients One study compared quality of life in HPV-positive patients and HPV-negative patients using the EORTC QLQ-C30 Four studies compared quality of life between HPV-positive and HPV-negative patients at more than one time point n = 3), with differences only significant when the quality of life scores were higher in HPV-positive patients. Others found no significant differences between the groups at any time point (n = 2).Overall, these longitudinal studies found inconsistent results when comparing quality of life in HPV-positive patients and HPV-negative patients. Some reported HPV-positive patients with a combination of both higher and lower quality of life scores than HPV-negative patients depending on the time points (n = 23) were conducted in the USA n = 4) n = 3) n = 2) n = 2) n = 2) n = 1) n = 1) n = 1) n = 1) n = 40) Forty-one papers from 37 studies assessed knowledge about HPV and HNC Studies assessing knowledge of HPV and HNC included samples of dental students Knowledge of the association between HPV and HNC varied across study populations and the questions asked . All theBased on the NICE quality appraisal checklists for the quantitative studies, 27 studies were designed or conducted in a way that minimised bias, nine studies were partly designed or conducted to minimise bias and had aspects of the study design that were unclear, and 13 studies were either unclear on aspects of the study reported or may not have addressed all potential sources of bias. No studies were assessed as having significant sources of bias across all aspects of the study design. Most studies described the source population well, used reliable and valid outcome measures, measured outcomes that were relevant and used appropriate analytical methods. Of 25 studies in which it was relevant to carry out a power calculation, only eight did so. Many of the studies had small samples and so could not be generalised to the source population. For the two qualitative studies, both were clear in the purpose of the study, carried out the data collection appropriately, were clear on the context in which the study was carried out, conducted reliable analysis, provided convincing findings and drew relevant conclusions. Both studies were unclear about whether the relationship between the researcher and participants had been considered. Both studies were considered to be designed to have minimised bias.This review is the first to draw together the emerging literature on the psychosocial implications of an HPV-related HNC diagnosis and awareness of the link between HPV and HNC. Quality of life was measured in the HPV-related HNC patient population, with inconsistent results found. Quality of life in those with HPV-positive HNC was found to be higher, lower or equivalent to those with HPV-negative HNC. In longitudinal studies, irrespective of the instrument used, quality of life in patients was at its lowest 2–3 months after diagnosis. In some studies, quality of life almost returned to baseline levels after 12 months. The UWQOL was the instrument used in three of the 10 studies included in this review. This scale is specific to HNC and measures 12 different domains as single-item questions. To allow for comparisons across studies, it would be ideal to have a well-validated, standardised measure that could be used in all studies. As previously reported, it is difficult to make generalised statements about quality of life that can aid in clinical decision making, due to inconsistencies in the design of quality of life instruments for HNC and a lack of unified reporting standards Use of other psychosocial measures was limited, with only one other primary research study measuring domains other than quality of life. This one study found clinically meaningful levels of distress in 30% of patients, but relatively low levels of self-blame The relationship between HPV and HNC is not well-known across most populations in the studies included here. The most knowledgeable group about HPV as a risk factor for HNC were second year dental students, dentists and head and neck surgeons (>85%), compared with one study finding that less than 1% of US adults knew that HPV is a risk factor for HNC. Awareness levels ranged across a variety of samples of the general population, dentists, students and specific sexually orientated groups, from 18 to 67%. Almost half the studies included dentists, dental hygienists or dental students, suggesting that the role dentists have to play in HPV and HNC is being increasingly recognised and educating them about HPV as a risk factor is important. All the questions were recognition questions rather than recall and so may not represent the true knowledge of participants as previous studies have found awareness to be higher in participants when responding to recognition questions when compared with recall Adhering to PRISMA guidelines ensured this review was carried out systematically. By including quantitative and qualitative studies in the review, we avoided exclusion of any eligible and relevant studies. As a number of different instruments were used to measure quality of life and at different points in the patient care continuum, it was difficult to compare across studies.A limited number of studies have measured the psychosocial impact of a diagnosis of HPV-positive HNC and those few that have, have only measured this in patient populations. Future work is needed with the partners of HPV-positive HNC patients and health professionals caring for these patients. The limited knowledge of the association between HPV and HNC among the public also indicates the need for research to explore the information that these populations are receiving. The development of collaborations between behavioural scientists and clinicians in this field will help to ensure that awareness of the role of HPV in HNC is raised, and that the adverse psychological consequences associated with diagnosis are understood and minimised.


The genital skin of males hosts a diversity of HPV genotypes and uncharacterized HPV genotypes. Previously we demonstrated that a specific viral genotype was not identified in 14% of all genital specimens  using the Roche Linear Array method. Our goal was to identify and assess the prevalence of individual HPV types among genital HPV unclassified specimens collected in the HIM Study population, at enrollment, and examine associations with socio-demographic and behavioral characteristics.Genital skin specimens of men that were considered unclassified  at enrollment were typed by sequencing amplified PGMY09/11 products or cloning of PGMY/GP+ nested amplicons followed by sequencing. PGMY/GP+ negative specimens were further analyzed using FAP primers. HPV type classification was conducted through comparisons with sequences in the GenBank database.Readable nucleotide sequences were generated for the majority of previously unclassified specimens (66%), including both characterized (77%) and yet uncharacterized (23%) HPV types. Of the characterized HPV types, most (73%) were Beta [β]-HPVs, primarily from β-1 and β-2 species, followed by Alpha [α]-HPVs (20%). Smokers (current and former) were significantly more likely to have an α-HPV infection, compared with any other genus; no other factors were associated with specific HPV genera or specific β-HPV species.Male genital skin harbor a large number of β-HPV types. Knowledge concerning the prevalence of the diverse HPV types in the men genital is important to better understand the transmission of these viruses.The online version of this article (doi:10.1186/s12879-014-0677-y) contains supplementary material, which is available to authorized users. Human papillomaviruses (HPVs) are a diverse group of circular double-strand DNA viruses of approximately 8.000pb. Persistent infection with high-risk HPV is not only the major etiological factor for cervical cancer development but also for a high proportion of tumors of the vagina, vulva, penis, anal canal and oropharynx .L1 sequence of a viral genome differs by at least 10% from that of all characterized types . Rec. RecL1 sed types -8]..L1 sequeDuring the last decade, there has been growing interest in understanding HPV natural history and related diseases among men. The HPV Infection in Men (HIM) Study is an ongoing, prospective genital HPV natural history study of over 4.000 men aged 18–70 years residing in Brazil (São Paulo), Mexico (Cuernavaca), and the United States . In this study, over 66% of men tested positive for HPV at their first study visit; however, the viral type could not be identified in 14% of the genital specimens using the Linear Array method  . Our goaMen were enrolled between 2005 and 2009 and reported no prior diagnosis of genital warts or anogenital cancers, and had no recent symptoms of or treatment for a sexually transmitted infection, including HIV/AIDS. Men completed a pre-enrollment (baseline) visit, were enrolled on completion of their second (enrollment) visit two weeks post-baseline, and subsequently followed approximately every six months for up to four years. Details of the HIM Study cohort are described elsewhere ,11]. Th. Th11]. At each study visit, participants completed a risk factor questionnaire and underwent a clinical examination of the external genital skin. Exfoliated cells were obtained from the coronal sulcus/glans penis, penile shaft, and scrotum using Dacron swabs , and these samples were further combined and stored at −80°C. HPV DNA was extracted using the QIAamp Media MDx Kit . Samples were PCR amplified using PGMY09/11 generic primers and genotyped using the Roche Linear Array . This technique allows testing for the presence of 37 α-HPV types commonly detected at the cervix  . SamplesInitially, purified DNAs were HPV genotyped by direct sequencing of PGMY09/11 primers PCR amplimers or cloning of these amplicons followed by sequencing. Next, 1 μl of PGMY09/11 negative product was used in a nested PCR using GP5+/6+ primers  and posiThe prevalence and genotype-distribution of unclassified genital HPV infections were estimated among all men enrolled in the HIM Study before December 2008. Infections were considered HPV-negative, HPV-positive for a characterized type, HPV-positive for an uncharacterized type, or untyped . Characterized HPV types were further classified according to genus and species. Socio-demographic and behavioral risk factors thought to be associated with presence of 1) a specific genus , and 2) a specific β-HPV species were evaluated using exact Pearson chi-square tests and Monte Carlo methods. All statistical tests were two-sided and attained statistical significance at α = 0.05. Analyses were performed using SAS version 9.3 .Of the 3105 men enrolled in the HIM Study through December 2008, 1126 (36.3%) were HPV negative at their enrollment visit, 1572 (50.6%) had at least one of the 37 α-HPV types detected in the Linear Array assay, and 407 (13.1%) had an unclassified HPV type detected. Of the 407 samples with unclassified HPV at enrollment, 404 were available for additional characterization. These include 165, 134, and 105 men from the USA, Brazil and Mexico, respectively. Table HPV type distribution of previously unclassified HPV infections is shown in Table The genotype-specific distribution of characterized HPV types is found in Figure Of the risk factors, only cigarette smoking was significantly associated with detection of α-, β-, or γ-HPV types Table ; smokersRecently we reported our initial observations concerning the broad distribution of β- and γ-HPV types in genital specimens of men participating in the HIM Study at enrollment through three years of follow-up . We thenAmong the 404 samples analyzed, 4.5% were truly HPV negative, i.e. PCR negative using any of the three primers sets, suggesting that a small proportion of unclassified HPV detection presumably represents spurious amplification. In 30.0% of the specimens, unreadable sequences were generated after direct sequencing of FAP54/69 PCR products; among these the presence of more than one HPV type is suspected . This hyOverall, unclassified HPV detection in HIM participants was significantly associated with younger age, white race, and non-Hispanic ethnicity. β-HPV types were detected among individuals residing in three countries and with diverse habits; however, slight differences in participant characteristics were demonstrated in men with α-HPVs versus β-HPVs, though none of these differences achieved statistical significance. In contrast to α-HPV prevalence in the genital region of men from the HIM study , β-HPV DHPV characterization of skin specimens from healthy individuals and squamous cell carcinomas of the skin (SCC) indicated that HPV types of β-2 species predominates in tumor samples . In the epidermodysplasia verruciformis , ce, ceepideciformis ,33] and andepideciformis ,34]. Ne. Neepideciformis . Most stciformis . At presDetection of HPV types not previously assigned by Roche´s Linear-Array in the genitals of participants of a natural history study of HPV in men was significantly associated with younger age, white race, and non-Hispanic ethnicity. Among these HPVs, we detected a broad range of α- and β-HPVs. Further research is needed to determine how these cutaneous HPV are transmitted.Ethical approval was given by the University of South Florida (IRB# 102660), Ludwig Institute for Cancer Research, Centro de Referência e Treinamento em Doenças Sexualmente Transmissíveis e AIDS, and Instituto Nacional de Salud Pública de México.


P = 0.03). The OR was stronger when only people under 60 years were included . Cooking with charcoal or firewood, and cigarette smoking, both increased the odds of developing OSCC . There was no significant difference in HPV detection or alcohol intake between cases and controls. We conclude that HIV infection and exposure to domestic and cigarette smoke are risk factors for OSCC, and HPV immunization unlikely to reduce OSCC incidence in Zambia.There is emerging evidence that esophageal cancer occurs in younger adults in sub-Saharan Africa than in Europe or North America. The burden of human immunodeficiency virus (HIV) is also high in this region. We postulated that HIV and human papillomavirus (HPV) infections might contribute to esophageal squamous cell carcinoma (OSCC) risk. This was a case–control study based at the University Teaching Hospital in Lusaka, Zambia. Cases were patients with confirmed OSCC and controls had completely normal upper endoscopic evaluations. A total of 222 patients were included to analyze the influence of HIV infection; of these, 100 patients were used to analyze the influence of HPV infection, alcohol, smoking, and exposure to wood smoke. The presence of HIV infection was determined using antibody kits, and HPV infection was detected by polymerase chain reaction. HIV infection on its own conferred increased risk of developing OSCC (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.0–5.1;  Esophageal cancer is the eighth most common cancer globally and the sixth most common cause of cancer deaths Despite a well described increase in adenocarcinoma, esophageal squamous cell carcinoma (OSCC) remains the predominant type of esophageal cancer worldwide Sub-Saharan Africa is considered home to more than 60% of all human immunodeficiency virus (HIV)-infected people Three meta-analyses have concluded that human papillomavirus (HPV) infection has a role in the development of esophageal cancer We undertook this case–control study to explore risk factors of OSCC in Zambia. We focused on HIV and HPV infections as infective agents that could be independently increasing the occurrence of OSCC, especially among young patients in Zambia. In addition, the lifestyle risk factors of smoking, alcohol, and exposure to wood smoke were evaluated.This study was conducted at the University Teaching Hospital (UTH) in Lusaka, Zambia from October 2013 to May 2014. UTH is the only combined secondary and tertiary hospital in the country, and offers full time endoscopy services. The unit offers standard endoscopic evaluation using high-definition Pentax London, United Kingdom (EG2990i) gastroscopes. Patients attending this unit are referred from all parts of the country.All patients attending the unit during the study period were considered for enrollment. Consent for study participation was obtained before the endoscopy. Between October 2013 and May 2014, 67 patients with esophageal lesions suspected to be esophageal cancer gave consent to participate in the study. Of these, 61 had histologically confirmed esophageal cancer, including 58 (95.1%) OSCC and 3 (4.9%) adenocarcinoma. Adenocarcinoma patients were excluded from the analysis. Eight esophageal cancer cases were also excluded due to the unavailability of an appropriate control during the study period. Therefore, 50 OSCC patients were enrolled and matched by age (±3 years) and sex to 50 controls. Initial analysis showed that the association of OSCC with HIV infection was very close to being significant, which suggested that the sample size was too small to show an effect. To clarify the influence of HIV infection, we increased the power of the study by combining these data with 122 patients (27 cases and 95 controls) obtained from a preliminary case–control study conducted at the same unit between July 2011 and January 2012. This case–control study had the same inclusion and exclusion criteria as outlined above, but no frozen samples were available for HPV analysis. With these data sets merged, we conducted further statistical analysis of the HIV effect, as outlined in the results below. We, therefore, analyzed a total of 222 patients with 77 cases and 145 controls.During the endoscopy, patients with lesions that were suspected to be esophageal cancer were designated as cases. A careful examination of the lesions was performed, and its location defined as follows: 15–24 cm, upper third; 24–32 cm, middle third; and 32–40 cm, lower third After the endoscopic procedure, 5–10 mL of venous blood was drawn from the study participants; serum was extracted and stored at −80°C for later determination of the presence of HIV antibodies.A simple questionnaire was used to collect data on the lifestyle risk factors for esophageal cancer from both the cases and the controls. We also collected information about symptoms that were present.μm sections, stained with hematoxylin and eosin for 1 h, and then examined using standard diagnostic criteria for OSCC. This included the presence of nuclear atypia and evidence of invasion.Six biopsies per participant were placed in formalin and sent to the histopathology laboratory. These biopsies were processed to 3 The frozen sera were thawed to room temperature and tested for the presence of HIV antibodies with Determine test kits  following the manufacturer's instructions. Unigold  kits were used as a confirmatory test for all the samples that tested positive with Determine. K. Z. conducted these tests and she was blinded to the allocation of the samples.μL was used, and DNA extracts were frozen at −20°C until further testing. For each specimen, 10 μL was used for the polymerase chain reaction (PCR) step of the DNA ELISA kit HPV SPF10 , which uses biotin-labeled SPF10 primers that target a conserved 65 bp region of the HPV L1 gene for broad-spectrum amplification. PCR products were stored at 4°C for less than 24 h before subsequent analysis. For each specimen, 10 μL of PCR product was tested in the SPF10 ELISA and/or SPF10 LiPA25 (LBP) assay, performed per the manufacturer's instructions. The ELISA assay uses streptavidin-coated plates to capture biotin-labelled PCR products, followed by hybridization with a cocktail of labelled HPV-specific probes, which is detected with a conjugate and visualized by a substrate. The presence or absence of HPV DNA is determined by comparing the optical density of the PCR product to a cut-off value. The LiPA25 is a reverse line blot assay where denatured PCR products hybridize with specific oligonucleotide probes immobilized on membrane strips. Following hybridization and washing, streptavidin-conjugated alkaline phosphatase binds to biotinylated PCR products, and bands are visualized by a substrate. Due to limited ELISA reagents, nine specimens were solely tested using LiPA. The worker who performed the HPV testing (A. C. B.) was blinded to the case–control status of all specimens. In addition to kit controls, external quality assurance specimens were used as known positive controls. Positive controls and negative controls were used for each step , and the results of controls were as expected.DNA was extracted from frozen esophageal biopsy specimens using a Qiagen QIAmp DNA Mini Kit , according to the DNA Purification from Tissues protocol. A final elution volume of 200 P value less than 0.05 was considered statistically significant. Using STATA, we performed a stepwise unconditional logistic regression to assess the relative contributions of different exposure variables  to the risk of developing OSCC.Data were analyzed using STATA 13 . For categorical variables, the Fisher's exact test was used, and for continuous variables the Kruskal–Wallis rank tests were used. To analyze the effect of HIV infection in strictly matched case–control pairs, we also used McNemar's test. Odds ratios (ORs) with 95% CIs were derived to estimate the association between exposure variables and OSCC. A Ethical approval was obtained from the University of Zambia Biomedical and Ethics Committee (reference number 001-06-13).P = 004), as shown in TableThe baseline characteristics of the cases and controls were similar Table. The meaThe full description of esophageal tumor characteristics was available in 46 of the 50 cases included in the analysis. These results showed that most of the tumors were either in the upper or the middle part of the esophagus and had some degree of luminal occlusion Table.Analysis of 50 OSCC cases and 50 controls showed that cooking with charcoal or firewood within the household increased the odds of developing OSCC Tables and 2. COf the 92 biopsy samples available for analysis, two cases and one control were positive for HPV (TableP = 0.04) (TableP = 0.64). There were significantly more males among the cases  than the controls and , P = 0.02. The presence of HIV infection did not differ between the two sexes, P = 0.852. A total of 21 (27.3%) cases and 42 (54.5%) controls were below the age of 45 years (P = 0.88). The presence of HIV infection did not differ significantly between cases and controls below the age of 45 years . These data are not shown in the tables. We also found that 43 (55.8%) cases and 80 (55.1%) controls were below the age of 60 years (P = 1.00) and there were significantly more HIV-positive patients among the cases than the controls (TableP = 0.006)  Table. To conf04) Table. There wof 21 27.% cases aof 21 27.% cases aof 21 27.% cases aIn recent years we have observed a worrying trend of increased occurrence of OSCC in young Zambian adults. Identifying the risk factors for these cancers is clearly a matter of great importance for gastroenterology in this region of southern Africa, and may unlock important clues to the etiopathogenesis of OSCC generally. In this paper, we report an investigation into the association of OSCC with various lifestyle risk factors, and the possible influence of HIV and HPV infection on the occurrence of OSCC among Zambian adults. We found that HIV infection independently increased the odds of developing OSCC. We further found that the use of firewood or charcoal as a means of cooking in the home, and cigarette smoking but not alcohol intake, increased the odds of developing OSCC. HPV infection does not appear to explain the occurrence of OSCC in Zambian adults.The prevalence of HIV infection in the Zambian population is high (12.5% in very recent data) There is no clear consensus on the role of HPV in the development of esophageal cancer. Results from different studies have been inconsistent; Syrjänen et al. suggested that this could be because of geographic variations in the populations being studied P < 0.001) Exposure to wood smoke has previously been reported to increase the risk of developing esophageal cancer. In a study involving 99 cases and 223 controls in Brazil, exposure to woodstoves was found to increase the risk of esophageal cancer (OR 4.42; Established risk factors for esophageal cancer include smoking, alcohol Reilly This is the first study that prospectively collected data on the age distribution of esophageal cancer patients in Zambia, and we have found that 28% were below the age of 45 years. This is similar to our previous findings in gastric cancer cases in which 21% were below 45 years The outcome of esophageal cancer patients in limited resource countries such as Zambia tends to be very poor. One of the postulated reasons is due to late presentation for medical assistance. For the 50 OSCC patients enrolled into this study, their symptoms had been present for an average of 17.7 weeks, ranging from 1 to 52 weeks. This clearly shows that there is a need to sensitize this population to seek medical assistance as soon as symptoms of dysphagia start to develop, to improve the treatment outcomes.In conclusion, HIV infection and exposure to domestic and cigarette smoke are risk factors for OSCC. HPV infection and the use of alcohol do not appear to play a large role in OSCC in Zambia.


Mounting evidence affirms HPV testing as an effective cervical cancer screening tool, and many organized screening programs are considering adopting it as primary testing. HPV self-collection has comparable sensitivity to clinician collected specimens and is considered a feasible option in hard-to-reach women. We explored women’s intentions to HPV self-collect for cervical cancer screening from a cohort participating in a Canadian randomized controlled cervical cancer screening trial.Women aged 25–65 were invited to complete an online survey assessing intentions to be screened with HPV testing instead of the Pap smear. The survey was based in the Theory of Planned Behaviour and questions were included to assess women’s intentions to self-collect for HPV. Demographic characteristics of women who intended to self-collect were compared with those who did not. Demographic and scale variables achieving a p-value <0.1 in the univariate and bivariate analyses were included in the stepwise logistic regression model. The final model was created to predict factors associated with women’s intentions to self-collect an HPV specimen for cervical cancer. Odds ratios were calculated with 95% confidence intervals to identify variables associated with a woman’s intention to self-collect for cervical cancer screening.The overall survey response rate was 63.8% (981/1538) with 447 (45.6%) reporting they intended to self-collect, versus 534 (54.4%) reporting they did not. In the univariate analysis, women with more than high school education were more likely to self-collect. Women who intended to receive HPV testing versus the Pap smear were 1.94 times as likely to be in favour of self-collection and those who intended to self-collect had significantly higher attitudinal scores towards HPV self-collection. The adjusted odds ratio and 95% confidence interval from the multivariate analysis demonstrated attitude towards self-collection was the only significant variable predicting a woman’s intention to self-collect .The primary predictor of a woman’s intention to HPV self-collect for cervical cancer screening was her attitude towards the procedure. From a program planning perspective, these results indicate that education and awareness may be significant contributing factors to improving acceptance of self-collection and subsequently, improving screening attendance rates.The online version of this article (doi:10.1186/1471-2458-14-1060) contains supplementary material, which is available to authorized users. Over the past 50 years, screening with cytology (Pap smear) has significantly decreased cervical cancer incidence and mortality in countries where it has been practiced effectively , 2. HoweIt is now well established that persistent infection with a high-risk genotype of the human papillomavirus (HPV) is necessary for the development of cervical cancer and its precursors , 7. MounIn British Columbia (BC), cervical cancer screening is managed provincially, through a population based cervical cancer screening program. In the past 30 years, incidence and mortality rates for cervical cancer have declined and remain low, reflecting the impact of organized population-based screening . In 2011As organized settings begin to plan for the introduction of primary HPV testing for cervical cancer screening, it will be essential for program planners to address methods to improve participation for women who do not routinely attend for cervical cancer screening. The use of self-collection offers an important opportunity to improve uptake in non-attenders for screening. In this evaluation, we determined women’s intentions to self-collect an HPV specimen for cervical cancer screening in the setting of an HPV testing based screening program.FluidSurveys (http://www.fluidsurveys.com) was the online survey software utilized for the purposes of this evaluation. Participants entered data on the website which was then downloaded into CSV files for analysis.Study participants for this evaluation were recruited through the HPV FOCAL Study, a randomized controlled, three-armed trial conducted in British Columbia (ISRCTN79347302) , 18. Appintention to perform that behaviour [The Theory of Planned Behaviour (TPB) , 20 was ehaviour . The Theehaviour . All iteAt the beginning of the survey, women were provided with some brief background information on human papillomavirus, which included information on HPV prevalence, transmission, its role in cervical cancer and the reasons for use of HPV testing in cervical cancer screening (See Appendix 1). The survey assessed women’s intentions to be screened for HPV for cervical cancer instead of Pap smears; women’s intention to be screened for HPV at 4 year screening intervals, and; screening for HPV at 4 year intervals commencing at 25 years of age . Each vaSurveys were reviewed for completeness and where duplicate surveys were identified, the first complete survey was used in the analysis and the second was discarded. Response rate was calculated according to the American Association for Public Opinion Research . ResponsI would be willing to collect my own sample/specimen for cervical cancer screening’. Participants responded to the statement with a seven point Likert scale . The responses were dichotomized so that those who responded >4 were coded as ‘intending to self-collect’ and participants who responded ≤4 as ‘not intending to self-collect’. In addition, women’s attitudes towards self-collection were evaluated from responses to the statement ‘Collecting my own sample for cervical cancer screening would be… ’.The primary endpoint for this evaluation was response to the statement ‘Demographic characteristics of survey responders and non-responders were compared using data collected from the larger HPV FOCAL Trial. All FOCAL Trial participants are asked to complete a demographic questionnaire upon entry, with questions addressing such variables as marital status, ethnicity, smoking and sexual history. Descriptive and univariate analyses of demographic characteristics of survey respondents were performed, including median age, marital status, education, sexual history, ethnicity and smoking history, categorized by women who intend to self- collect, versus those who did not. Continuous variables were compared with Student’s t-tests and Kruskal-Wallis tests as appropriate and categorical variables were compared with Chi-Square test. Women’s intention to self-collect a sample for cervical cancer screening was calculated with 95% confidence intervals and variables with p-values <0.05 were deemed significant.Theory of Planned Behaviour[Scale items were analyzed according to methods for the ehaviour. See AddDemographic characteristics of women who intended to self-collect were compared with those who did not intend to self-collect with Chi-square, Student’s t-test and Kruskal-Wallis as appropriate. Multi-collinearity of psychological scales that achieved an item correlation with Cronbach’s alpha >0.5 was assessed with Pearson correlation coefficient. Overall scale scores and mean scores with standard deviations for scale results between those who intended to self-collect and those who did not intend to self-collect were calculated. Mean results with standard deviations between scales that had acceptable agreement  and no collinearity were compared using Student’s t-tests. Demographic  and scale variables that achieved a p-value <0.1 in the univariate and bivariate analyses were included in the stepwise logistic regression model. The model was created to predict factors associated with women’s intentions to self-collect a specimen for cervical cancer. The dependent variable for the model was ‘intention to self-collect’ . Logistic regression analysis was conducted and odds ratios calculated for significant variables with 95% confidence intervals to identify correlates of a woman’s intention to self-collect for cervical cancer screening. Analyses were conducted with SAS 9.3.The survey was administered from May through September 2011. Of the 2,459 women who had completed participation in the FOCAL trial at that time, email addresses were available for, and invitations to complete the survey were sent to 2,016 women (eligible population)  indicating consistency of responses to the attitude measurements for self-collection.Of the 981 women who completed the surveys, 447 (45.6%) reported they intended to self-collect, versus 534 (54.4%) who reported they did not intend to self-collect Table . Women wA woman’s responses to other questions in the survey can be directly correlated with her opinions regarding self-sampling. Variables that have a significant difference in scores between those who intend to self-collect and those who do not, include subjective norms indirect  and direct , which may indicate that the opinions of those who are important to them, as well as others such as family physician, friends, partner, the BC Cancer Agency, may influence the woman’s decision to self-collect or not  than women who did not intend to receive HPV testing.Based on the univariate and bivariate analyses, variables included in the regression model were those with a p-value less than 0.1 including: the psychological variables for indirect and direct subjective norms; perceived behavioural control; intent to receive HPV testing versus the Pap smear; and attitude towards self-collection. Age and education were also included in the model. We used a stepwise regression analysis that did not retain insignificant explanatory variables. The only variable of significance in predicting a woman’s intention to self-collect a cervical specimen was her attitude towards self-collection  Table .Table 4It is anticipated that vaccination against oncogenic HPV types will decrease the incidence of cervical cancer on a population level in the future when girls who have been vaccinated begin to reach the age for cervical cancer screening sometime in the next 10–15 years. However, despite the promising effects widespread HPV vaccination will have, screening for cervical cancer will still need to occur. With the growing body of evidence demonstrating the efficacy of primary HPV testing with cytology triage for detecting precancerous lesions and subsequent decreases in the incidence of cervical cancer , it is aIn our study, of the 981 women who completed the survey, 447 (45.6%) indicated they intended to self-collect versus 534 (54.4%) reporting they did not intend to self-collect. Overall, the results of this analysis show that regardless of other variables, the primary predictor of a woman’s intention to HPV self-collect for cervical cancer screening is her attitude towards the procedure. This is important from a program planning perspective, indicating that concerted efforts towards comprehensive education and awareness campaigns on the value of self- collection and HPV testing in preventing cancer could be the significant contributing factors to improving acceptance of self-collection and subsequently improving screening attendance rates.In the current study, when asked if they would be willing to collect their own specimen for HPV, more than half of all responders were not willing to self-collect. This rate was higher than expected, given results of previously published literature which found that women generally approved of the procedure and had positive attitudes towards it , 14, 28.In this study, the women who intended to be screened with primary HPV testing compared to the Pap smear were significantly more likely to be in favour of self-collection. This is relevant, given our previous study showed that 84.2% of women intended to be screened for cervical cancer with HPV testing versus the Pap test . HoweverThe results of the descriptive analysis showed women who had more than high school education were more likely to self-collect than women with less than high school education. However, education was not significant in the adjusted regression model and the only predictor of significance was a woman’s attitude towards self-collection. This is consistent with other published research demonstrating no definitive associations between a woman’s attitude towards self-collection and demographic variables such as education, socioeconomic status and age , 29. HisTo our knowledge, women in this survey had no experience performing cervical sample self-collection. Other trials demonstrating positive attitudes towards self-collection assessed women’s attitudes towards the procedure after having obtained a self-collected specimen , 14. A rThis study demonstrates that the primary predictor of a woman’s intent to self-collect a vaginal sample for HPV testing is her attitude towards this procedure. Although the women in this study are currently engaged in clinician-based screening in an organized program, these findings illustrate that comprehensive education is essential for successful implementation of self-collection to both keep women engaged in screening and to improve screening attendance rates. Culturally competent educational materials should be available in a variety of formats to include information about HPV, its association with cervical cancer, and the importance of screening. Additionally, to ensure acceptance of self-collection by women, they should be provided with information regarding the ease, effectiveness and safety of the procedure. Further research is recommended to explore the attitudes surrounding, and intentions to self-collect, for women who do not regularly attend for clinician-based cervical cancer screening.Introductory information provided to survey respondentsHere is some background information for you to consider before you complete this survey.The human papillomavirus (HPV) is a common virus that can infect the cervix (part of a woman’s womb). It is now known to be the cause of cervical cancer. Women develop HPV infections in the cervix after having sexual activity with a partner who is infected with HPV. However, HPV is so common that over 75% of sexually-active women will have an HPV infection of their cervix sometime during their life. Most women who find out they have an HPV infection in the cervix after the age of 30, were infected with HPV years before. Over 90% of women who are infected with HPV in the cervix get rid of the infection naturally. It is only women who have longstanding infections with certain types of HPV who may be at risk for developing cervical cancer. Women may not have known it in the past, but it is these same HPV infections that are the most common reason for abnormal Pap smears.Right now in BC, women start cervical cancer screening once they become sexually active. We now know that testing for HPV infections in the cervix is more accurate than the Pap smear for predicting whether or not a woman will develop cervical cancer.LWS MPH BN RN: Project Manager, HPV FOCAL Study, Population Oncology, BC Cancer Agency (BCCA). Vancouver, Canada.FK MSc in Statistics: No current affiliation.DJV, FRCP(C): Medical Leader BC Cervical Cancer Screening Program, BCCA, Vancouver, CanadaMK, MD FRCP(C): Medical Head Hepatitis Clinical Prevention Services, Associate Medical Director, BC Centre for Disease Control (BCCDC) Public Health Microbiology and Reference Laboratory. Professor Dept. of Pathology and Laboratory Medicine, University of British Columbia (UBC). Vancouver, Canada.SBG DrPH: Professor of the Practice and Interim Chair, Health Policy and Management,SH DrPH: Clinical Associate Professor, Director, Doctoral Program in Health Leadership.Gillings School of Global Public Health. University of North Carolina (UNC) at Chapel Hill. North Carolina, USA.Research Fellow, Center for Health Promotion and Disease Prevention. Department of Health Policy and Management, and Department of Nutrition, Gillings School of Global Public Health.AJC PhD: Vice President, Population Oncology, BCCA. Adjunct Professor Statistics, UBC. Vancouver, Canada.ELF, DrPH FRSC FCAHS: James McGill Professor in the Departments of Oncology and Epidemiology & Biostatistics, Director, Division of Cancer Epidemiology, and Chair, Department of Oncology, at McGill University. Fellow of the Canadian Academy of Health Sciences and of the Royal Society of Canada. Editor-in-Chief of Preventive Medicine. Montreal, CanadaGSO, MD MSc FCFP DrPH: Medical Director Clinical Prevention Services, BCCDC. Associate Professor, Faculty of Medicine, UBC. Vancouver, Canada.UNC at Chapel Hill. North Carolina, USA.Theory of Planned Behaviour.(DOC 104 KB)Additional file 1:


Association between verrucous carcinoma (VC) of the head and neck and human papillomaviruses (HPV) is highly controversial. Previous prevalence studies focused mostly on α-PV, while little is known about other PV genera. Our aim was to investigate the prevalence of a broad spectrum of HPV in VC of the head and neck using sensitive and specific molecular assays. Formalin-fixed, paraffin-embedded samples of 30 VC and 30 location-matched normal tissue samples were analysed, by using six different polymerase chain reaction-based methods targeting DNA of at least 87 HPV types from α-PV, β-PV, γ-PV and μ-PV genera, and immunohistochemistry against p16 protein. α-PV, γ-PV and μ-PV were not detected. β-PV DNA was detected in 5/30 VC (16.7%) and in 18/30 normal tissue samples (60.0%): HPV-19, -24 and -36 were identified in VC, and HPV-5, -9, -12, -23, -24, -38, -47, -49 and -96 in normal tissue, whereas HPV type was not determined in 2/5 cases of VC and in 6/18 normal tissue samples. p16 expression was detected in a subset of samples and was higher in VC than in normal tissue. However, the reaction was predominantly cytoplasmic and only occasionally nuclear, and the extent of staining did not exceed 75%. Our results indicate that α-PV, γ-PV and μ-PV are not associated with aetiopathogenesis of VC of the head and neck. β-PV DNA in a subset of VC and normal tissue might reflect incidental colonization, but its potential biological significance needs further investigation. Papillomaviridae family, consisting of more than 170 different types. They cluster into five genera: Alphapapillomavirus (α-PV), Betapapillomavirus (β-PV), Gammapapillomavirus (γ-PV), Mupapillomavirus (μ-PV) and Nupapillomavirus (ν-PV). Human papillomaviruses can be found as commensals colonizing human epithelia, but their clinical importance lies in association with several cutaneous and mucosal lesions varying from benign warts to several types of cancer. According to preferential site of infection, HPV have been traditionally divided into »mucosal« types (α-PV), predominantly found in anogenital lesions and »cutaneous« types , typically isolated from skin and hair follicles. The clinically most important genus α-PV associates more than 40 different HPV types that can be further divided into low- and high-risk types defined by their risk of progression to malignancy. Low-risk types (the most important being HPV-6 and HPV-11) are mainly associated with benign lesions, such as anogenital warts and laryngeal papillomas, and high-risk types (the most important being HPV-16) play a leading role in the development of cervical, anal and vaginal carcinoma, and a proportion of other cancers, including a subset of squamous cell carcinoma (SCC) of the head and neck Human papillomaviruses (HPV) are a heterogenous group of epitheliotropic DNA viruses from the Verrucous carcinoma (VC) is a rare variant of well-differentiated SCC. It arises most commonly on the mucosa of the head and neck, predominantly in the oral cavity and the larynx, but it can also arise on other locations, such as the skin, anogenital region, urinary bladder and oesophagus. Verrucous carcinoma is characterized by an exophytic, wart-like macroscopic appearance. Microscopically, it consists of filiform projections, lined by thick, well-differentiated keratinizing squamous epithelium, composed of one to a few layers of basal cells and multiplied, voluminous cells of spinous type, lacking cytologic atypia. The invasive nature of VC is difficult to assess, but at the stromal interface, it always exhibits a well-defined, pushing margin. It grows slowly and even though it is locally destructive, it is believed to be unable to metastasize. The prognosis is therefore significantly better in VC than in conventional SCC The aetiopathogenesis of VC of the head and neck has not been fully elucidated. It is generally believed that conventional SCC and VC share similar aetiological factors To elucidate the controversial aetiologic role of HPV in VC of the head and neck, and to investigate the prevalence of HPV genera other than α-PV in this tumour, we performed a comparative study of the HPV prevalence in VC and normal tissue of the head and neck, using six different PCR protocols for detection of at least 87 HPV types from α-PV, β-PV, γ-PV and μ-PV genera. In addition, an immunohistochemical analysis of p16 protein expression was performed.The study was approved by Ethical Commission of Republic of Slovenia.Surgical biopsy samples of cases of VC of the head and neck were included, diagnosed at the Institute of Pathology, Faculty of Medicine, University of Ljubljana during a period of 10 years. In all of them, routine diagnosis of VC was made on the basis of the following criteria For the purpose of this study, all biopsies were reviewed by two pathologists (N.G. and N.Z.). Those containing foci of ‘conventional’ SCC were not included in the study, as well as cases in which not enough tissue was available for immunohistochemistry and molecular analyses.As normal tissue controls, biopsy samples of microscopically normal mucosa and skin were included, obtained from patients who underwent surgery for various conditions other than VC. The normal tissue samples were matched to VC by location.All tissue samples were routinely collected during surgery, fixed in 10% buffered formalin for 24 hrs and embedded in paraffin. Haematoxylin and eosin stains were made for routine histopathological diagnostics. For the purposes of our study, representative tissue blocks were retrieved from archives of the Institute of Pathology, Faculty of Medicine, University of Ljubljana.Total DNA was extracted from the tissue blocks sectioned at 10 μm, as previously described Several »in-house« and commercially available PCR-based methods were used to detect DNA of at least 87 HPV types from the genera α-PV, β-PV, γ-PV and μ-PV. For all PCR experiments, 50–100 ng (5 μl) of DNA was used per a 25 μl reaction Plus DNA Polymerase kit . The reaction mixture contained template DNA, 2.5 μl of 10× CoralLoad PCR Buffer with 15 mM MgCl2, 200 μM of dNTPs, 0.625 U of HotStarTaq Plus DNA polymerase, 0.5 μM of each of the primers and water up to 25 μl. The cycling conditions were 95°C for 5 min., followed by 40 cycles of 94°C for 30 sec., 50°C for 1 min. and 72°C for 1 min., followed by final extension at 72°C for 10 min. and cooling the reaction mixture to 4°C. To definitely exclude the presence of clinically most important α-PV types, all the samples were additionally tested with a reverse line-blot hybridization-based INNO-LIPA HPV Genotyping Extra Amp test , capable of recognizing 28 different HPV types . The test was performed strictly following the manufacturer's instructions.For the detection of α-PV, a touchdown GP5+/GP6+ PCR protocol For the detection of β-PV, a reverse line-blot hybridization-based RHA Kit Skin (beta) HPV test  was used, enabling detection of at least 25 different HPV types, including HPV-5, -8, -9, -12, -14, -15, -17, -19, -20, -21, -22, -23, -24, -25, -36, -37, -38, -47, -49, -75, -76, -80, -92, -93 and -96. The assay was performed as instructed by the manufacturer, except that the number of PCR cycles was increased from 35 to 40.For the detection of γ-PV, a C4F/C4R PCR protocol was used For the detection of HPVs from the genus μ-PV (HPV-1 and -63), a SK-PCR was used Immunohistochemistry was performed on all samples. Tissue sections were cut from the paraffin blocks at 4–5 μm. Staining was performed in the BenchMark XT immunostainer . After antigen retrieval with Cell Conditioning 1 (CC1) buffer  at 95°C for 30 min., the slides were incubated with primary antibodies against p16  for 30 min. Immunoreactivity was visualized using the iVIEW DAB Detection Kit , according to the manufacturer's instructions. Sections were counterstained with haematoxylin.The reaction was scored as follows: 0 (<5% of positive cells), 1 (>5% and <25% of positive cells), 2 (>25% and <50% of positive cells), 3 (>50% and <75% of positive cells), 4 (>75% of positive cells). The pattern of staining was also analysed . Cells with nuclear or cytoplasmic staining or both were considered positive.P < 0.05.For statistical analyses, Fisher's exact test was used. Differences were considered statistically significant when Thirty cases of VC were included. There were 21 males and nine females, aged 31–83 years (mean 60.63). The tumours were located in the oral cavity (15 cases), in the larynx (10 cases), in the nasal cavity (two cases) and on the skin (three cases). In the control group, there were 30 samples of the normal mucosa and skin, matched to VC by location, samples were obtained from 13 males and 17 females, aged 19–83 years (mean 53.47).The 268-bp fragment of human beta-globin gene was successfully amplified in all tissue samples included in the study. Human papillomaviruses DNA was not detected in any of the HPV-negative control samples . All water blanks used to control for PCR contaminations were negative for internal control amplification.P = 0.001). Among β-PV positive cases of VC, there were 1/15 case from the oral cavity, 2/10 cases from the larynx and 2/2 cases from the nasal cavity. No β-PV DNA was detected in VC of the skin. Human papillomaviruses-19, -24 and -36 were detected each in one case. In two cases of VC, HPV type was not further determined. Among β-PV positive cases of normal mucosa and skin, there were 11/15 cases from the oral cavity, 4/10 cases from the larynx and 3/3 cases from the skin. HPV-38 and -96 were detected each in two cases and HPV-5, -12, -23, -24, -47 and -49 each in one case. In two cases, two different HPV types were co-present . In six HPV-positive normal tissue samples, HPV type was not further determined.Results of the HPV detection and typing are summarized in Tables Results of immunohistochemical analysis of p16 protein expression are presented in Tables In the normal mucosa and skin, score 0 was assigned in all but two cases (6.7%) which were assigned score 1. The reaction was predominantly cytoplasmic, with occasionally accentuated nuclei. The staining pattern was mostly patchy, mosaic, predominantly in the basal/parabasal cells. Scores 2, 3 and 4 were not assigned in any of the normal tissue samples.P = 0.005). However, no statistical difference existed for the expression levels of p16 with scores 3 and above .The expression of p16 was significantly higher in VC than in normal tissue (We analysed the prevalence of at least 87 HPV types in VC and normal tissue of the head and neck using six PCR-based assays. α-PV, γ-PV and μ-PV were not detected in any of the samples. β-PV DNA was found in 16.7% of VC and in 60% of normal tissue samples. We also analysed the immunohistochemical expression of p16 protein and found that it was significantly higher in VC than in the normal tissue. However, the reaction was predominantly cytoplasmic and only occasionally nuclear, and the extent of staining never exceeded 75% of cells. These results suggest that VC of the head and neck is not induced by α-PV, γ-PV or μ-PV, while the significance of β-PV DNA in VC remains controversial.etc. Verrucous carcinoma was named after its characteristic wart-like appearance, leading to the assumption that it is aetiopathogenetically related to HPV infection Our results of p16 immunohistochemistry also speak against the causal role of α-PV in the pathogenesis of VC. p16 immunohistochemistry is commonly used as a surrogate marker of high-risk α-PV infection in different malignant tumours, including anal, cervical and head and neck SCC. However, as noted in previous studies, it has to be interpreted with caution In addition to the broad spectrum of α-PV, we also analysed the prevalence of β-PV, γ-PV and μ-PV in VC and normal tissue. Interestingly, β-PV DNA was detected in 16.7% of VC and in 60% of the normal tissue samples. This finding is in accordance with some previous studies reporting a relatively high prevalence of β-PV in the skin and oral mucosa in general populations In contrast to β-PV, we detected no γ-PV and μ-PV DNA in our samples, confirming previous observations that γ-PV and μ-PV are less frequent in the head and neck than β-PV et al. et al. Two previous studies investigated a broad spectrum of HPV in VC. Del Pino e.g. tissue samples versus swabs In addition to 30 cases of VC, our study also included 30 normal tissue control samples, matched to VC by location and sample type. With some exceptions et al. After our manuscript had been submitted for publication, an interesting paper was published by Patel In conclusion, to the best of our knowledge, this is the largest study in which a broad spectrum of HPV types was comparatively analysed in VC of the head and neck and location-matched normal tissue controls, using highly sensitive and specific molecular assays. Our results suggest that α-PV, γ-PV and μ-PV are not associated with the aetiopathogenesis of VC. Even though the presence of β-PV DNA in a subset of VC and normal tissue samples could merely reflect an incidental tissue colonization, the potential biological significance of β-PV in VC needs further investigation. The list of HPV-induced SCC variants in the head and neck is increasing


Since introduction of the human papillomavirus (HPV) vaccine, there remains low uptake compared to other adolescent vaccines. There is limited information postapproval about parental attitudes and barriers when presenting for routine care. This study evaluates HPV vaccine uptake and assesses demographics and attitudes correlating with vaccination for girls aged 11–12 years. A prospective cohort study was performed utilizing the University of Virginia (UVA) Clinical Data Repository (CDR). The CDR was used to identify girls aged 11–12 presenting to any UVA practice for a well-child visit between May 2008 and April 2009. Billing data were searched to determine rates of HPV vaccine uptake. The parents of all identified girls were contacted four to seven months after the visit to complete a telephone questionnaire including insurance information, child’s vaccination status, HPV vaccine attitudes, and demographics. Five hundred and fifty girls were identified, 48.2% of whom received at least one HPV vaccine dose. White race and private insurance were negatively associated with HPV vaccine initiation . In the follow-up questionnaire, 242 interviews were conducted and included in the final cohort. In the sample, 183 (75.6%) parents reported white race, 38 (15.7%) black race, and 27 (11.2%) reported other race. Overall 85% of parents understood that the HPV vaccine was recommended and 58.9% of parents believed the HPV vaccine was safe. In multivariate logistic regression, patients of black and other minority races were 4.9 and 4.2 times more likely to receive the HPV vaccine compared to their white counterparts. Safety concerns were the strongest barrier to vaccination. To conclude, HPV vaccine uptake was higher among minority girls and girls with public insurance in this cohort. Human papillomavirus (HPV) is the most common sexually transmitted disease in the United States and is associated with 99% of all cervical cancers ,2. In thA vaccine to protect against human papillomavirus was first introduced in 2006 in the United States . This quadrivalent HPV vaccine protects against viral types 6, 11, 16, and 18, which are known to cause approximately 90% of genital warts and 70% of cervical cancer [It is imperative that the HPV vaccine reach all populations in order to significantly impact rates of cervical cancer. The National Immunization Survey for Adolescents (NIS-Teen) documents adolescent immunization for ages 13–17. These data show national HPV vaccination rates fall below recommended levels and are significantly lower than other adolescent vaccinations . PreviouIn March 2007, the Virginia governor signed into law House Bill 2035  requiring the HPV vaccine for girls on or after their 11th birthday but allowing parents to exempt their child via a verbal opt out effective 1 October 2008 . Given tThis study was conducted to determine whether insurance status and other demographic factors play a role in HPV vaccine uptake and completion among girls presenting for a well-child visit at age 11–12 years old. This study also documents baseline vaccination rates for the year prior to enactment of the Virginia school mandate.This prospective cohort was developed by searching the University of Virginia Clinical Data Repository (CDR) at 3 month intervals for all girls aged 11–12 years presenting for a well-child visit between May 2008–April 2009. These dates were chosen to capture the vaccination uptake for the school year prior to enactment of the Virginia HPV vaccine mandate. This included all patients seen at UVA-supported family medicine practices and pediatric practices in a 50 mile radius including urban, suburban, and rural populations. Clinical and demographic data were also collected, including age, race, insurance status, and vaccination status for HPV, Meningitis, Tdap, and Varicella. The primary outcome was HPV vaccine uptake as defined by receipt of ≥1 dose confirmed by billing data. Final collection of HPV vaccine uptake and number of injections received was collected six months after the last identified well-child visit. Of note, this study only evaluated girls as the HPV vaccine had not yet been approved for use in boys at the time of data collection.To provide greater in depth analysis of these findings, the parents of these girls were then contacted 4–7 months after the initial well child visit to allow for time to complete the HPV vaccination series in three batched samples. A cohort of parents/guardians of the original population agreed to participate in the telephone questionnaire.A 50-item telephone questionnaire was developed that took the parents approximately 10 min to complete. The questionnaire included validated questions on insurance status and demographics, previously studied questions on HPV vaccination attitudes and behaviors designed utilizing constructs from the Health Belief Model , as wellParents were contacted first with an advance letter and either called in to the survey center or verbally consented to participate over the telephone. The University of Virginia Center for Survey Research (CSR) trained all interviewers and conducted all interviews and all answers were entered to a database for later data analysis. The parent or guardian who said they were the most familiar with the child’s health history was asked to participate in the survey. To reduce non-response bias CSR made several efforts at “conversion calling” for households where a potentially eligible respondent had refused to participate once or twice.p < 0.05 considered statistically significant. Relative risk and 95% confidence intervals were calculated for all cohort data in 2 × 2 tables. Likert scales to assess vaccination attitudes were dichotomized for agree or disagree with the attitude. After preliminary analysis, demographic, knowledge, and attitude data from the telephone questionnaire were utilized in multivariable logistic regression. All factors significantly associated with HPV vaccine uptake or refusal (p < 0.1) were retained in the model. The final model was fit with backwards stepwise elimination of nonsignificant variables. Sensitivity analysis was conducted to verify the relationship between the variable and the outcome of HPV vaccine uptake.Data analysis included frequency distribution of race, insurance status, and vaccination status in the original population and the cohort participating in the telephone questionnaire using SPSS version 18.0  and SAS, version 9.1 . The primary outcome of HPV uptake ≥1 dose received was converted to a binary variable. Associations were determined by chi-square test for categorical variables with Based on demographics of the pediatric population at UVA in 2008, 60% of patients had private insurance. An HPV vaccination rate of 40% based on the National Immunization Survey from 2008 was used as a baseline assumption . In ordeFive hundred and fifty 11–12 year old female patients were identified in the total population of girls seen for a well-child visit between May 2008–April 2009. Of these patients, 72.5% were nonhispanic white race, 53% had private insurance, and 48.2% were vaccinated against HPV during the study period .In this population, there were noted to be significant associations of HPV vaccination with insurance status and race. Girls with private insurance were less likely to receive the HPV vaccine compared to girls with public insurance or self-pay. Conversely, girls with public insurance were 36% more likely to be vaccinated as compared to girls with private insurance .Further, nonhispanic white girls presenting for well child visit were overall almost 30% less likely to initiate vaccination compared to all minority girls . Compared to nonhispanic whites, black girls were 36% more likely to have received at least 1 dose of the HPV vaccine. There were no significant differences in HPV vaccination completion rates by race among those who received at least one dose with 84/172  of nonhispanic whites and 71/154  of minority girls completing the three injection series.All 550 families from the original population were considered for participation in the telephone questionnaire .Four hundred and thirty-two households with a working number were approached for participation in the questionnaire and 242 parents or guardians agreed to participate in the telephone interview for a response rate of 56%.  See All parents confirmed the child had a recent visit to the doctor. Eighty-nine percent of participants went with the child to the documented visit, of whom 79% remember the doctor discussing the HPV vaccine. The majority of respondents confirmed that the child had been seeing this physician for 5 years or greater.Overall, 92% of parents were aware of the HPV vaccine, and 85% reported that the HPV vaccine was recommended for their child. In regards to HPV vaccine knowledge, 69% of respondents agreed that the vaccine protects against cervical cancer, but only 20% also identified that the quadrivalent vaccine protects against genital warts. The majority of respondents (59%) agreed that the HPV vaccine is safe. Twenty percent of parents felt that their child did not need the HPV vaccine. There were no statistically significant differences in these attitudes compared by race.vs. 47.5%, respectively; p = 0.003). By comparison, whites were more likely to have received the meningococcal vaccine , and rates were not significantly different for Tdap and varicella vaccines . Again, there were no significant differences for the other recommended childhood vaccines  were also significantly more likely to be vaccinated. Safety concerns were the strongest attitude barrier to vaccination . InsuranIn this prospective cohort study, minority girls were more likely to receive the HPV vaccine compared to their nonhispanic white counterparts. In particular, race correlated more with vaccination initiation than insurance status, beliefs about safety and efficacy, recommendation by the pediatrician, and perceived susceptibility although these factors likely also played a role in the parents’ decision to have their child vaccinated. The CDC’s National Immunization Survey-Teen in 2011 documented a similar trend for higher vaccination rates among minorities . HoweverAmong girls presenting to the doctor for a well-child visit in this study, privately insured patients were less likely to receive the HPV vaccine than girls with Medicaid or no insurance. This may be related to coverage and reimbursement issues which can be heterogeneous among private payers, possibly resulting in more out-of-pocket costs for parents. By comparison, all children who qualify for Medicaid and/or are underinsured for vaccinations and meet certain financial cutoffs are covered by the Federal Vaccines for Children program for all vaccines recommended by the CDC, including the HPV vaccine. The NIS-Teen survey also noted a difference in vaccination by socioeconomic status with 46.4% of girls below the poverty level initiating vaccination compared to 35.8% of girls at or above the poverty level choosing to be vaccinated . It is pThis study evaluated HPV vaccination given uniform access to care in a single cohort of girls being seen for well child checks in the same health care system. This is a strength of the study as it controls for regional differences in provider counseling and issues in access to patient care. This research utilized prospective data collection and objective billing data for confirmation of vaccination status allowing for the most accurate determination of vaccination. In addition, utilization of a professional survey group for interviews, validated questionnaire, and a piloted study technique allows for high quality subjective data. This study is limited by its small sample size and evaluation of only a single health care delivery system. For the follow-up questionnaire, we had a relatively low response rate but this is comparable to similar telephone surveys conducted on HPV vaccination . In regaThis study documents HPV vaccination rates, attitudes and barriers prior to initiation of a statewide mandate requiring girls in Virginia to receive the HPV vaccine prior to their 11th birthday for school admission and begins to identify further areas that need elucidation. These data will serve as the baseline for a comparison study of HPV vaccination rates and counseling 5 years after enactment of the mandate. This study is uniquely positioned to address this question given the objective data capture through the billing database combined with a validated parental survey and uniform access to care. Further, documented differences by race and insurance status seen with HPV vaccination but not with other adolescent immunizations will serve as the baseline for post-mandate comparisons. The follow-up study is slated to be conducted starting in August 2013. These data may have implications beyond a single state given similar trends in differential rates of uptake by race seen at a national level.In this study, we found that parents report high rates of understanding that the HPV vaccine is safe, effective, and recommended for adolescent girls. Privately insured patients had lower vaccination rates compared to those with public or no insurance. Racial differences exist with minority girls having higher HPV vaccination rates than their white counterparts. Future studies will be necessary to evaluate whether the verbal opt-out mandate in Virginia will have any effect on these racial differences.


Cancers are the second most common cause of non-accidental deaths in Iran, after cardiovascular mortality. Although most cases of esophageal squamous cell carcinoma (ESCC) in the USA and western populations have been attributed to high levels of exposure to tobacco and alcohol, but in Iranian populations, other risk factors especially infectious agents have been postulated as possible causes, particularly human papillomavirus (HPV). This study aimed to determine the prevalence and the types of HPV infection in biopsy samples taken from non-cancerous esophageal lesions during upper endoscopy.A total of 80 non-cancerous esophageal samples were collected in parafinnated blocks of tissue archives in pathology. After DNA extraction, qualitative PCR (qPCR) was performed using the HPV L1 primer pairs MY09/MY11 and then genotyping was performed in HPV DNA positive by Real time PCR.From 80 cases, 29 (36.3%) were qPCR positive. Using the Real-time PCR method, a total of 14 HPV genotypes were assessed. We detected HPV-11 as a dominant type in this study and we did not find any type of HPV-16 and 18 genotypes. In this study, HPV-II was the most common type in esophageal samples, in contrast we have found no oncogenic HPV like HPV 16 and 18 which are the most known responsible factors of ESCC in other countries. Cancers are the most common cause of death throughout the world. It is estimated that the overall incidence of different types of cancers will have increased by 45% in developed countries by 2030. Many reports indicate that cancers are the second most common cause of non-accidental deaths in Iran, after cardiovascular events , 2. CarcBoth histological subtypes of esophageal malignancies, including squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are highly lethal with a current five-year survival of less than 10% . In the Human papilloma virus (HPV) is a viral agent associated with esophageal cancer thus far. HPV, especially genotypes of 16 and 18, were the major cause in uterine cervical carcinoma and has a strong association with cancers of the vulva, anus, penis, oropharynx and esophagus . HPV typIn many Iranian studies, esophageal SCC was associated with HPV 16 but not HPV 18 . Most inThis is true for both the high-risk and low-risk HPV types. Sometimes HPV infections are not clear and results in cell changes which may predispose the infected to the development of future cancers . The preSubjects: A total of 80 non-cancerous esophageal samples were collected. The presenting symptoms in 48 patients was dyspepsia, 20 patients had heart burn, and 12 patients with dysphagia. 57 samples were provided from Shahid Beheshti Hospital, one of the big hospitals in Babol, a city in Mazandaran, North of Iran; 23 samples were obtained from Central Lab of Amol, a city, west of Babol. Demographic and medical information including age, gender, resident, smoking and type of lesion were obtained from the patients’ medical records. Based on pathology diagnosis, the parafinnated blocks of tissue-archive in two centers in patients with non-cancerous esophageal lesion were entered in our study. DNA extraction and Real Time PCR: The methods were described previously  by AmpliSense HPV HCR genotype FRT PCR Kit for High-Risk genotyping using AmpliSense HPV 6/11 FRT PCR Kit for the detection of Low-risk genotyping .The patients were 42 to 90 years old and their mean±SD age was 65±12.3 years. The characteristics of patients and the frequency of HPV infection were presented in Using the Real-time PCR method, a total of 14 genotypes including HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 were analyzed. As seen in table 2, we detected HPVs-11 (in 4 cases), 33 (in one case), 56 (in 2 cases) and HPV-56 (in one case) of patient with inflammation. Also, HPVs-11, 39 and 52 were detected in only one case of patient with dysplasia. The most prevalent genotype was HPV11  of the HPV positive cases  and the second more prevalent genotype was HPV 56 with 6.9% (2.29). Also, HPV was found in 8 inflammatory samples in 4 cases, HPV 33 and 58 in one case and HPV 56 in 2 cases). In 12 dysplastic samples, 3 genotypes of HPV including HPV-11, 39 and 52 were detected.In our study, from the 80 cases with tissue diagnosis of non-malignant esophageal lesions, the prevalence of HPV-DNA in these samples with Real Time PCR was 36.3%. We reported, 20 (39.2%) HPV DNA in esophagitis samples and others were 29.6% , 58.8%  and 26% Many studies were performed in different geographic parts of Iran, from northeast of Iran , northweOther studies from many countries including China (0- 71%) , 32, 33;Yahyapour et al. reported HPV in 27% of ESCC patients. They found one case of HPV-16 and one case of HPV-18. They reported the highest genotypes HPV 11 & 45. Also, they reported the etiology of HPV 16 & 18 for infection of by cancer in the North of Iran . TherefoIn our study HPV prevalence in ≤55 years was 26.3% and ≥55 were 39.3% (p>0.05). Also, infection to HPV in man was detected 37.5% versus 34.3% in women. Also, we found HPV infection in urban patients was more than rural patient samples (P=0.001) and those results were not reported in other studies. To compare, in Qi’s study in China, HPV prevalence in ≤55 years were 25% and >55 was detected in 30.9%; also, they reported HPV infection in men about 26.5% versus 41% in women .In the study of Tornesello, 51.8% of infection specimens those less than 50 years old and 11.1% older than were 60 years. Also, 70.4% of males and 29.6% of females were HPV DNA positive . But, DaIn conclusion, this study evaluates the prevalence of HPV infection in non-cancer tissue samples in Mazandaran, North of Iran for the first time in our knowledge. From the results of this study, HPV DNA prevalence in non-cancerous samples of esophagus in North of Iran in comparison to other geographic study is considerable. Some oncogenic types of HPV (HPV-16 and 18) were not found in our samples. Therefore, we suggest that there are different infections of HPV genotypes in patients with non-cancerous lesion of esophagus in the North of Iran with other parts of Iran and other countries.


Human papilloma virus(HPV) accounts for most cases of cervical cancer with high risk HPV(hrHPV) genotypes largely responsible. The objective is to ascertain the distribution of oncogenic strains of human papilloma virus genotypes and predisposing risk factors in women presenting for cervical cancer screening in Nigeria.A cross-sectional study of 80 women who presented for cervical cancer screening. The biodata of the participants, the presence of risk factors to HPV were recorded and hrHPV were identified using PCR technique. The information obtained was processed using the SPSS version 20 software. Results were presented in tables, test of significance and association done using student's t-test and Odds ratio, with P value < 0.05 as significant.The age range of patients was 19-62 years with prevalence of hrHPV of 10%. HrHPV are more in patients with more than one life time sexual partner , multiple sexual partners , early coitarche  and previous STI . Four hrHPV genotypes: 16, 18, 31 and 35 were detected.HPV genotype 18 was predominant in Port Harcourt, Nigeria. High risk sexual behaviours are associated with acquisition of hrHPV. Cervical cancer is a malignant lesion of the cervix. The squamous cell carcinoma constitute about 90-95% of cases while adenocarcinoma make up about 5-10% . About 92p(1-p)/d2; where P is the HPV prevalence in Ibadan Nigeria [This was a cross sectional prevalence study carried out, between August 2014 and December 2014 in the cancer screening centre of UPTH on women who presented for cervical cancer screening in the University of Port Harcourt Teaching Hospital, Port Harcourt. All women between the ages of 15 to 70 years were included in the study after due counseling and obtaining consent to be involved in the study. Women were excluded from the study if they refused to give consent, had total abdominal hysterectomy, had been treated for premalignant lesion of the cervix, were adequately immunized against the human papilloma virus or had received antineoplastic therapy or immunotherapy. The sample size was determined using the Leshe-kish formula for single proportion  which isA structured study proforma was administered on each of the women. The following information was obtained from the women: age, occupation level of education, marital status and parity. Other information obtained from the women included the history of smoking, age at coitarche; number of lifetime sexual partners and history of previous sexually transmissible infections. The presence of partners who had multiple sexual consorts was also ascertained. The phone numbers of the participants were collected for disclosure of the results, counseling and advice on further management where necessary.The collection of the sample was done in the presence of a female nurse who also served as a chaperone. In collecting the sample, the women were placed in lithotomy position, the cervix was exposed using the bivalve speculum and then inspected. The specimen for the HPV genotyping was collected using the cyto-brush, cut short at the brush end and inserted into an already numbered specimen bottle, which contained a physiological saline. All collected samples with the cyto-brush were packaged in an ice pack in a container and were sent to the Safety Molecular Pathology laboratory at Enugu, Nigeria through a prearranged courier service. The Pathology department of the UPTH has collaboration with the Safety Molecular Pathology laboratory Enugu. The cervical samples were analyzed for the presence of all possible oncogenic strains of HPV DNA using Real time Polymerase Chain Reaction (PCR). In determining the HPV genotypes where present, a PCR mixture was prepared in a tube. The mixture contained the DNA sample (extracted from the cyto-brush scrapings), primers (forward and reverse primers) and reaction buffer from magnesium chloride. Other contents of the mixture included deoxynucleosides triphosphates (dNTPs) and Taq DNA polymerase.Statistical analysis was done using computer software Statistical Package for Social Science version 20.0. Frequency tables were generated and the results tested of significance using student t-test and chi-square. The age-specific prevalence and the contribution of other socio-demographic factors were computed. The risk of acquiring hrHPV was estimated with odds ratio. Statistical test of association was carried out at the level of significance set at P value <0.05 at 95% confidence interval. Ethical considerations: Ethical clearance for the study was obtained from the ethics committee of the Teaching Hospital before the commencement of the study.A total of 80 women who met the inclusion criteria were recruited for the study. The age range of the participants was 19-62 years. The median age was 39 ± 5 years. Eight women out of the 80 women who participated in the study were positive for the oncogenic strains of human papilloma virus giving a prevalence of 10%.In The prevalence of human papilloma virus (HPV) in this study was 10% which is similar to the adjusted global prevalence of 10.41% in a study on epidemiology and transmission dynamics of genital HPV infection . HoweverThe human papilloma virus type 18 was the predominant genotype identified. A review of patients with proven cervical cancer in Ghana and South African also identified serotype 18 as being contributory in about 17.2% of cases reviewed . The stuIt was observed that patients with higher parity (>3) had about two times higher risk of human papilloma virus infection. HPV. Similar observations were noted by Fadahunsi et al in Nigeria . VariousThe influence of the sexual orientation of women as a contributory factor to the occurrence of hrHPV is evident in this study as majority of the women with more than one lifetime partner and those with spouses with multiple sexual partnersare associated with higher risk of acquiring oncogenic strains of HPV. The lack of statistical significance may be linked to the population size of affected persons relative to the general sample size, nevertheless the positive association between these factors is evident by the OR ratios analyzed. This role of multiple sexual partners in acquiring HPV infection was also observed in a study done in Columbia . The preThis study is limited by the fact that it is hospital based; hence community based-study is strongly advised to increase the power of the study. The association of human immunodeficiency virus infection with higher incidence of oncogenic strains of human papilloma virus had been demonstrated by various studies but that was not taken into consideration in this study, hence a survey on the effect of human immunodeficiency virus infection in this environment is advocated in subsequent reviews.The high prevalence of the high risk HPV genotypes noted in this study exposes the magnitude of the burden of HPV infection in our environment. There is need to increase the level of surveillance on females at risk of cervical cancer in this environment, since significant proportion of highly oncogenic strains with a high propensity to transformation to malignancy were observed in this study. Furthermore, there is need to encourage Government agencies to promote a more inclusive HPV vaccine such as Gardasil-9 in their national immunization scheme which has a wider coverage as against those currently available in most countries. This should be administered to girls at the appropriate age if transmission of HPV is to be reduced. There is also need for sexual behaviour modification in order to reduce the impact of the risks factors identified in this study.Oncogenic strains of HPV are responsible for 99% of cervical cancerNatural history of cervical cancerHPV genotyping is a screening method for cervical cancerThis is the first study of its kind in South-South NigeriaRevealed a relatively high prevalence of oncogenic strains of HPV in the population studied, reinforced the sexual links in the acquisition of HPV virus and identified genotype 18 as the predominant HPV present in the women in the South-South NigeriaHighlighted the need for an urgent sexual reorientation to reduce prevalence of high risk HPV strains and highlighted the importance of education in reducing the prevalence of oncogenic strains of HPV


In addition, having multiple lifetime sexual partners was a significant risk for oral-genital HPV coinfection . These findings provide a basis for further understanding the natural history and transmission dynamics of oral HPV infection.Human papillomavirus (HPV) infection, a primary cause of genital cancer, is also related to the increasing incidence of oropharyngeal cancer among young men. Relatively little is known about the concurrence of oral and genital infection among healthy individuals. Oral and genital swab exfoliated cells were collected simultaneously from 2566 men in rural China. Using general primer-mediated (SPF1/GP6+) PCR and sequencing, HPV testing results were obtained from 2228 men with both valid oral and genital specimens (β-globin-positive). The prevalence of HPV infection was 6.7% in the oral cavity and 16.9% for the external genitalia. Among 43 men  with oral-genital coinfection, 60.5% (26/43) harbored an identical HPV type at both sites. The risk of oral HPV infection was higher among men with genital infection than among uninfected men (11.4%  Human papillomavirus (HPV) infection is an etiologic factor for cervical, anal and penile cancer35678However, whether oral HPV infection is associated with genital infection remains largely unknown, especially among men. Previous studies investigating the association of oral and genital HPV infection among men were based largely on particular high-risk groups such as university students, sexually transmitted disease clinic patients, HIV-infected men, or homosexual men101112131415101112131415Concurrence of oral and genital HPV infection has rarely been investigated in a general male population. Previously, we reported an overall oral HPV prevalence of 6% in 5410 25–65 year old healthy males and females in rural ChinaAmong 2721 eligible subjects, 2228 (81.9%) participants showed valid HPV DNA results for both oral and genital specimens. The 493 individuals not included in analysis were either non-responding (n = 155) or were negative for beta-globin (n = 338). These excluded subjects were more likely to work outside of the local area, show loss of teeth, have a history of oral disease, and report oral sex practices, but were less likely to have a smoking history . The medAmong 2228 men, 376 (16.9%) and 149 (6.7%) were positive for genital and oral HPV infection, respectively . Comparevs. 0.6, P < 0.001)  positive for HPV in both oral and genital specimens, 37.2% (16/43) had no types in common, 62.8% (27/43) were concordant for at least one type, and 60.5% (26/43) harbored exactly the same HPV type at both sites, including 18 men concordant for HPV-3, 4 men concordant for HPV-10, 3 men concordant for HPV-57, and 1 man concordant for HPV-29 . The Mon< 0.001) .vs. 5.7%, Adjusted OR = 2.3, 95% CI: 1.6–3.4)  . In the vs. 1 partner), as was the case for genital HPV infection , over 60.0% of these concurrent infections were completely type-specific concordant, and oral HPV prevalence was significantly higher among men with genital HPV infection than among those without. These data provide a basis for further understanding the natural history and transmission dynamics of oral HPV infection.Prevalence of oral HPV was significantly lower than on the external genitalia in healthy adult Chinese men, similar to what has been observed in other populations1810Among concurrent non-oncogenic HPV types found in this population, HPV-3, which has been rarely reported elsewhere, was the most dominant type. Since antibody against HPV-3 L1 was also frequently detected in serum from the same cohort22In this study, significantly higher prevalence of type-specific HPV in oral specimens was found among men positive for genital HPV of the same type, which is consistent with some but not all previous surveys1014Many studies have suggested that both oral and genital HPV infections are mainly sexually transmitted76This study has limitations. First, the nonparticipation and exclusion of participants because of specimen inadequacy may undermine the validity for generalizability of study results to some extent. Second, self-reported sexual behavior features may be subject to reporting bias. Additionally, despite a large population sample size, the low prevalence of oral-genital coinfection may limit our ability to identify some associations. This low prevalence of coinfection may also have rendered subgroup analysis of carcinogenic HPV impossible. Finally, due to the cross-sectional nature of this study, temporal relationship cannot be inferred. A longitudinal cohort study with rigorous follow-up is needed to evaluate the relationship of HPV acquisition at different anatomic sites and its relevant factors.In conclusion, our data suggested that HPV infections of the oral cavity and the male genitalia in the same individual were type-specifically correlated. Concurrence of oral-genital infections was associated with multiple sexual partners. Given that HPV-related oropharyngeal cancer appears to be on the increase, improved insight into the relationship of HPV infection at the oral cavity and other anatomical sites may help to inform and direct future prevention efforts, such as HPV vaccination.A population-based prospective cohort study of esophageal cancer and its associated determinants has been published previouslyExfoliated cells from oral cavity and genitalia were collected by an experienced clinician using saline-moistened cotton swabs, as described previously17A one-on-one computer-aided interview was carried out by a trained interviewer of male gender. Information regarding demographic characteristics, cigarette consumption (defined as 1 cigarette or more each day for at least 1 year), alcohol consumption (defined as use of Chinese liquor twice each week or more for at least 1 year), characteristics of sexual behavior , and self-reported history of oral disease in the preceding 12 months  was collected. Numbers of missing teeth were also recorded.2, and 0.8 U HotStarTaq polymerase . After a 15-min enzyme activation at 95 °C, 40 cycles of amplication  and a final extension at 72 °C for 10 min were carried out. Detection of HPV DNA was performed for the β-globin positive samples by amplifying a fragment of 184 bp in the L1 gene using a highly sensitive PCR primer set (SPF1/GP6+). The PCR was performed in a reaction mixture containing 50 ng template DNA, 0.4 μM each primer, 0.15 mM deoxynucleoside triphosphate, 1 × PCR buffer containing 1.5 mM MgCl2, and 0.8 U HotStarTaq polymerase. PCR conditions were as follows: preheating for 15 min at 95 °C, 45 cycles of amplification , and a final extension at 72 °C for 10 min. PCR products of HPV positive specimens were purified and then directly sequenced using an ABI 3730XL DNA Analyzer222517DNA was extracted and purified on a Biomek 3000 automated workstation with the E.Z.N.A.TM Mag-Bind Tissue DNA Kit . The β-globin gene was evaluated in all purified DNA samples . β-globin PCR mixture contained 50 ng template DNA, 0.2 μM each primer, 0.2 mM deoxynucleoside triphosphate, 1 × PCR buffer containing 1.5 mM MgClKappa value, percent agreement, and percent positive agreement were calculated to assess the concordance of HPV infection in paired oral and genital specimens from the same individuals. The McNemar’s test was used to evaluate the difference in the positivity of HPV infection in the oral cavity and on the external genitalia. To evaluate type-specific positive concordance, the analyzed observations were restricted to those positive for at least one site  and a Monte-Carlo simulation method (1000 iterations) was used for comparisons of observed concordant events and expected value30To identify independent determinants for HPV infection, exposure variables that showed statistical significance in univariate logistic regression analysis, together with factors previously reported to be relevant , were included in multivariate logistic regression models (Variance inflation factor was used to examine whether variables in multivariate models were collinear). To examine linear trends, ordered categorical variables were treated as continuous covariates in the regression analysis.For type-specific analysis to assess whether the presence of one specific HPV type in the oral cavity was associated with the presence of the same type in the genitalia, generalized estimating equations with an exchangeable correlation structure were used to account for possible correlations of different types of HPV. For groups of HPV types (i.e. any HPV type), infection of each type among the analyzed group for each individual was treated as one observation in the type-specific analysis. For instance, for any HPV type, each subject could have 43 HPV-type outcomes .P <0.05 were considered statistically significant. Statistical analyses were conducted using Stata 11.0 (Stata Corp.).All tests were two-sided and differences with How to cite this article: Liu, F. et al. Concurrence of oral and genital human papillomavirus infection in healthy men: a population-based cross-sectional study in rural China. Sci. Rep.5, 15637; doi: 10.1038/srep15637 (2015).