To investigate whether testing positive for human papilloma virus (HPV) in cervical screening has an impact on female sexual functioning.This study was designed as a single-center, prospective, descriptive-cross-sectional study and 300 women who received HPV testing in our hospital [HPV-positive (n=187) or HPV-negative (n=113)]. The Arizona Sexual Experiences (ASEX) scale and Female Sexual Functioning index (FSFI) were administered to study participants during face-to-face interviews.No significant differences were found between women who were HPV-positive and HPV-negative in sexual functions as assessed using the ASEX and FSFI scales . In addition, the analyses addressing whether sexual functioning was affected by a positive test result, at diagnosis or during the follow-up  revealed no significant differences between HPV-positive and HPV-negative women in sexual functioning (p>0.05). Sexual dysfunction was less common in married women than in the ASEX scale (p=0.03), and this difference was not detected when the FSFI scale was applied. The incidence of dysfunction was more frequent in working women than in retirees .Educational attainment, socioeconomic status, age, employment status, and marital status were found to have statistically significant effects on sexual functioning. Sexual functioning was affected by neither HPV test results (positive/negative) nor time from diagnosis. PRECIS: Human papilloma virus results of the patients does not related to sexual dysfunction.. Female sexual dysfunction is described as libido abnormalities, stimulation and orgasm problems, along with sexual pain.Female sexual function is defined as “the harmony in mind, senses and the individual’s body, which leads to the achievement of the personality, communication and love” ,4. Sexual function is affected by many factors such as menstruation, pregnancy, lactation, anogenital lesions, cancer, chronic systemic diseases, infertility, any conditions that might lead to sexual dysfunction including vaginismus, vaginal atrophy, vaginal stenosis, active vaginitis, hymenal stenosis, depression, use of any medicines, and alcohol and/or any chemical substance addiction,6,7.In Turkey, the prevalence of sexual dysfunction in women has been reported to range between 46.9% and 48.3%, the definition of sexual dysfunction was also changed in the diagnostic and statistical manual of mental disorders-fifth edition criteria. The classification was made simpler by reducing categories into three sections. Female hypoactive desire dysfunction, and female arousal dysfunction were merged into a single syndrome called sexual interest/arousal disorder. Similarly, the formerly separate dyspareunia and vaginismus are now called genitopelvic pain/penetration disorder. Female orgasmic disorder remains in place.Along with the changes in human sexual response model from linear to Basson’s circular model. The transmission of HPV may also occur through intimate contact without intercourse. An HPV screening program has been conducted in Turkey since 2009. Owing to these screening programs, HPV can also be diagnosed in asymptomatic women. Being an HPV carrier and having anogenital condyloma have been associated with anxiety, depression, and sexual dysfunction in previous studies,12. Women who tested positive for HPV may experience feelings of guilt, sadness, stigma, and embarrassment, which make them more concerned about sexual contact. The aim of this study was to investigate sociodemographic factors affecting female dysfunction along with HPV screening results.Human papilloma virus (HPV) is the most prevalent sexually transmitted disease worldwidest, 2017, and November 1st, 2017, were included in the study. The Arizona Sexual Experiences (ASEX) scale and the Female Sexual Function Index (FSFI) were administered to study participants during face-to-face interviews at diagnosis, before 2 weeks, 2 weeks-1 month, 1-3 months, 3-6 months, 6 months-1 year, and after 1 year. Each participant provided written informed consent. A total of 345 women aged 18 to 70 years who were referred for routine gynecologic exams with normal cervical smear results were included in the study. The exclusion criteria were pregnancy; lactation; anogenital lesions; cancer; chronic systemic diseases; infertility; any conditions that might lead to sexual dysfunction including vaginismus, vaginal atrophy, vaginal stenosis, active vaginitis, and hymenal stenosis; depression; use of any medicines; and alcohol and/or any chemical substance addiction. With all these evaluations, 300 patients were included and 45 patients were excluded from the study. The enrollment of the study was showed in  in 2000 to assess female sexual functioning. The validity and reliability of the Turkish version of the questionnaire has been established in a validation study. It is a 19-item inventory comprising six domains: desire, arousal, lubrication, orgasm, satisfaction and pain. This questionnaire reflects sexual functioning over the past one month based on subscores from six subscales and the FSFI total score. Subscale scores and the FSFI total score are calculated according to a scoring system developed by the investigators who developed the questionnaire. Domain scores are calculated by summing individual items in a given subscale and multiplying the sum by corresponding domain factor indicated in the relevant table, and the overall FSFI score is calculated by summing all subscale scores. In this study, response options were provided and individual subscale scores were calculated on a Likert-type response scale. A total score less than 26.55 indicates risk for sexual dysfunction. All questionnaires were reviewed in order to identify any possible inconsistency.This study was designed as a single-center, prospective, descriptive-cross-sectional study, and was approved by the Dr. Lütfü Kırdar Training and Research Hospital Local Ethics Committee (decision no: 2019/514/148/24). Women who received HPV screening in our hospital between August 1 to assess changes in sexual functioning and sexual dysfunction in patients on psychotropic medications. The validity and reliability of the Turkish version of the questionnaire has been established in a study conducted by Soykan. Female and male versions of ASEX are available. It is a five-item scale and items quantify sex drive, psychological arousal, physiological arousal, ability to reach orgasm, and satisfaction from orgasm, respectively. Each item is rated from 1 to 6 with possible total scores ranging from 5 to 30, sexual dysfunction is defined as total scores of 19 or more, or 5 or more on any item, or 4 or more on three items and strongly correlates with clinically defined sexual dysfunction,19. Sociodemographic data including age, educational attainment, marital status, household income, and number of children were recorded. Etiologic factors related to FSD were investigated via the ASEX and FSFI questionnaires. Also, the questionnaire subscores of the patients were investigated in terms of HPV screening results. The patients were followed up in order to clarify the effect that could arise afterwards.ASEX is a self-reported questionnaire that was developed by McGahuey et al. The SPPS 20.0 software  was used to analyze the study data. Data were presented as mean ± standard deviation, median (minimum-maximum), percentages, and frequency of variables. Repeated measures of analysis of variance (ANOVA) was analyzed using Mauchy’s Sphericity test and Box’s test of equality of covariance matrices. For comparisons of means, repeated measures ANOVA was used. If parametric tests  did not provide the preconditions, Greenhouse-Geisser (1959) correction or Huynh-Feldt (1976) correction or the Friedman test was used for corrections to the degrees of freedom. The corrected Bonferroni test was used for multiple comparisons. Normality and homogeneity of variances were prerequisites to analyze variables using the Shapiro-Wilk and Levene tests. In the analysis of data, the independent Samples t- test (Student’s t-test) was used in comparisons between two independent groups, if prerequisites were met, and the Mann-Whitney U test was used if prerequisites were not met. In comparisons among three or more groups, One-way ANOVA and Tukey’s honestly significant difference multiple comparisons test were used if prerequisites were met, and the Kruskal-Wallis or Bonferroni-Dunn’s multiple comparisons tests were used if prerequisites were not met. Fisher’s exact test and the chi-square test was used to analyze categorical data. When the expected frequencies were less than 20%, the Monte Carlo simulation method was used to include these frequencies in the analysis. The statistical significance level for these tests was set at p values of <0.05 and <0.01.A total of 300 women who met the inclusion criteria were included in the study. Cervical cytology samples were obtained. In the follow-up, results were explained to the patients and the ASEX and FSFI scales were administered to participants during this visit and follow-up visits at week 2, week 4, month 3, month 6 and month 12, thereafter. Study participants were stratified based on sociodemographic characteristics and the results of cervical cytology for HPV. The mean age of participants was 42  years. Sociodemographic Characteristics scale scores and smear results for HPV are summarized in The assessment of factors affecting total ASEX scale scores of the participants revealed that being aged 45 years and older (p=0.016), marital status (p=0.03), being employed (p=0.01), parity (p=0.011), and low income and high income levels (compared to middle income levels) (p=0.023) significantly increased the prevalence of sexual dysfunction . TestingThe assessments on whether testing positive affected FSFI subscores revealed no differences between women who were HPV-positive and HPV-negative in terms of desire (p=0.670), arousal (p=0.670), lubrication (p=0.490), orgasm (p=0.880), satisfaction (p=0.850), and pain (p=0.380) subscale scores .The comparisons between ASEX scores or FSFI total/subscores at diagnosis, week 2, week 4, month 3, month 6 and month 12 time points revealed that neither ASEX scores nor FSFI total/subscores differed significantly with time from diagnosis of HPV .. Demir et al. reported an HPV incidence of 31.8% among women aged 25-29 years and a decrease with age. Unlike other studies, this study could not demonstrate any potential effects of a diagnosis of HPV on sexual functioning. Furthermore, time from diagnosis had no effects on sexual functioning. Unlike our study, Ferenidou et al. concluded that women who were diagnosed as having HPV experienced negative feelings and a reduction in sexual desire. According to the results of a study conducted by McCaffery et al., testing positive for HPV might lead to anxiety, and necessary education should be provided to HPV-positive women after sharing test results. The results in our studies may be explained by the exclusion of women with anogenital lesions and abnormal Pap-smear results at screening. In addition, this study was the first and single study investigating the effects of a diagnosis of HPV and time from diagnosis on sexual functioning, and the differences in the results compared with studies conducted abroad might be explained by cultural differences. Psychosocial effects of HPV-linked diseases and abnormal cytology results have been demonstrated in previous studies. Previous studies showed that even positive screen results for HPV might have psychosocial consequences. These effects could cause anxiety, stress or reluctance to engage in sexual activity. Independently from cervical cytology results, it has been demonstrated that a positive HPV test alone might make women feel bad about sexual relationships. In our study group, sexual dysfunction scores at the time of detection of HPV positivity were examined and these scores were compared. However, it would be more meaningful to compare the scores of the same patient before the HPV test and the scores after receiving the HPV test results. This is the most important limitation of our research.The HPV carrier incidence was 62.3% in our population, which is much higher than in older studies (17.9%), which might be associated with this study being conducted in a tertiary center. Also, previous studies were conducted in a different region of Turkey and 8 years ago,27. The FSFI is widely used to investigate female sexual functioning and received a wide acceptance; the validity of the Turkish version has been established. In this study we also used the ASEX questionnaire in order to have more accurate results.Female sexuality has been increasingly investigated over recent years. New questionnaires and algorithms have been developed to ensure the objectivity of assessments. It has been reported that menopausal status has no negative impact on sexual functioning; however, stress, previous sexual experiences, and general health status are more important determinants of sexual health. In this study, we also observed that sexual functioning was better in older women compared with younger women. Reduced responsibilities and mother and child dependency could explain this observation. The increased prevalence of sexual dysfunction among women with children compared with woman without children also provides further support to this assumption. In the literature, several studies reported that the first delivery and breastfeeding might cause sexual dysfunction. A study assessing postpartum sexual functioning was conducted in the Netherlands and reported that older age at delivery was related to better sexual functioning.Previous studies investigated the associations between advanced age and sexual functioning and revealed similar rates of sexual problems between older women and younger women who were referred for routine gynecologic exams. In our study, educational attainment had no significant effects on ASEX total scores and FSFI total scores. In a study conducted by Laumann et al., the prevalence of sexual dysfunction and possible predictors of sexual dysfunction were investigated and a negative correlation was found between higher educational attainment levels (college graduates) and the prevalence of sexual dysfunction. In our study, no significant association was found. These results may be explained by the fact that sex education is not included in the school curriculum in our country and any information is hearsay or obtained by individuals on their own.In the literature, no association between educational attainment and sexual functioning has been clearly established. In this study, sexual dysfunction occurred less in the middle income group than in the other income groups. The assessment of income levels in combination with other variables indicated that sexual dysfunction was more likely among those with pre-existing depression and/or lower educational attainment, in addition to having a low income level. In previous studies, sexual dysfunction has been reported in more than one-third of women with more than 11 years of schooling. However, there are also contradictory studies in the literature. It is possible that we could not clearly demonstrate such differences because our population was not homogenous in terms of income levels. These differences might be clearly demonstrated in studies with larger and homogenous study samples. The effects of employment status on sexual dysfunction remained unclear in a recent study conducted in 2018, whereas partner’s unemployment was suggested as a risk factor. Sexual dysfunction was more prevalent in working women in our study. However, the nature of work and working hours were not investigated in our study, and potential effects of employment status on sexual functioning may be more clearly defined by taking these factors into consideration.A literature search on the effects of income levels on sexual functioning revealed that several publications reported an association between lower income levels and a higher prevalence of sexual dysfunction, whereas others reported the oppositeThis study is important because it is the first to investigate the effects of testing positive for HPV on sexual functioning in Turkish woman over an extended follow-up period. Furthermore, bias was avoided by using two different questionnaires.Educational attainment, socioeconomic status, age, employment status, and marital status were found to have statistically significant effects on sexual functioning. Sexual functioning was affected by neither HPV test results (positive/negative) nor time from diagnosis.


In current era of blue brain intelligence and technology access at ease, standardization of disease etiology demands extensive research to drop-down human papilloma virus associated head and neck squamous cell carcinomas impact at large. Present retrospection aims to estimate comparative association of human papilloma virus sub-genotypes in head and neck squamous cell carcinomas, critical analysis of existing research gap, treatment progress, co-infection, gender association, national status and challenges following Human papilloma virus led head and neck squamous cell carcinomas among world largest continent. Head and neck squamous cell carcinomas are not just like malignancies of uterine cervix, lymph nodes and breast cancers. Human papilloma virus led head and neck squamous cell carcinomas treatment directly impact Central nervous system in humans. Intriguingly, human papilloma virus mediated immune response increases patient survival, which indirectly transmit human papilloma virus in future generations and act as a potential threat developing neurogenic disorders. An objective based search strategy, following comprehensive and specific search approaches were made to retrieve recent 12 years research data from five different NCBI databases. Out of 300 shortlisted articles, only 24 principal studies met the inclusion criteria. Highest human papilloma virus prevalence (10.42 %) was found in South Asia, 5.8 % in South East Asia, 5.7 % East Asia, 2.5% in west Asia and no relevant updated data was found from central Asian continent. Highest prevalence (10%) of HPV genotype-16 was recorded in Asia among 3, 710 enrolled cases including 2201 males, 1149 females and 360 cases of unknown gender. While undifferentiated multiple HPV genotype prevalence was 5.5 % (204 cases). Lowest percentage of HPV sub-types 68, 72, 57, 39 were recorded respectively. Pakistan ranked top reporting highest number of HPV-16 cases, Taiwan HPV-18, India HPV-31, Japan HPV-35 and Singapore in HPV-16 and HPV-18 co-infection rates respectively. 2 = 81-88% at 95 % confidence interval), non-availability and limitations of reported studies from Asian sub-continents especially central Asia, western Asia and from south and south east Asia demand large scale collaborative research culture to standardize head and neck squamous cell carcinomas aetiology.Exact prevalence of HPV associated head and neck squamous cell carcinomas among Asian population is still debatable. Due to higher heterogeneity (P< 0.00001), I Classically HPV led squamous cell carcinomas of head and neck arise from oropharynx impacting multiple sites including, lip, tongue, eye, chin and nasopharynx as well . Globally HNSCCs are the sixth most common deadly malignancies, causing 350,000 deaths each year with annual incidence of 600,000 reported cases . While, study of National statistics office in United Kingdom reported 7,745 cases each year . Specifically, Oropharyngeal and tongue malignancies are predominant cancers in west. However, in general HNSCC a heterogenous group of tumours are shortly reported from South Asia instead of entire Asian continent . According to Faheem A et al study in 2009, HNSCC is considered second most prevalent type of cancer in Pakistani subjects alone with recorded incidence of 40.1% . Commencing comparative clinical aetiology of HNSCCs from Europe based case control studies. About (70-75%) HNSCCs cases are synergistically associated with tobacco and alcohol consumption accompanied by familial history . Whereas, (10-15%) HNSSCs cases are associated with decreased intake of fruit and vegetables . In contrast to European countries, betel-quid chewing also plays a major role in the development of malignant tumours focusing Asian subjects . Molecular biology of Head and neck carcinomas revealed that genetic mutations and chromosomal abnormalities, especially mutation of p53 gene involvement in development of head and neck cancers . Recent progression in research trends indicated decline in alcohol and tobacco induced HNSCCs. Whereases, Prevalence of HPV induced HNSCCs is increasing. Another supporting evidence suggest higher chances of HPV transmission during sexual behaviour in comparison to tobacco and alcohol consumption . Instead of HPV-genotypes independently, co-infection with Epstein Barr virus also errand development of nasopharyngeal carcinomas . Classical research reported 95% prevalence of HPV in cervical carcinomas and 12.8%-59.9 % association of HPV-Subtypes in HNSCCs, including HPV-35, HPV-33, HPV-31, HPV-18 and HPV-16. Which clearly highlights existing research gap focusing HPV subtype specific prevalence and exact role following HNSCCs . HPV led HNSCCs require progressive and meticulous treatment measures. After critical care and monitoring only five-year survival rate of 68% was possibly achieved yet. While delayed tumour detection and improper treatment may impact nervous system in humans. Intriguingly, HPV mediated immune response increases patient survival, which indirectly transmit HPV in future generations and act as a potential threat developing neurogenic disorders . Present retrospection aims to estimate comparative association of HPV sub-genotypes in head and neck squamous cell carcinomas among world largest continent. The main objectives include to critically analyse existing research gap, epigenetic treatment progress, multiple genotype co-infection, gender association, national status and challenges following HPV related head and neck squamous cell carcinomas among Asian people. Database search strategyAn objective based search strategy, following comprehensive and specific search approaches to retrieve recent 12.5-year research data from five different NCBI databases including PubMed, MeSH, PubMed Central, NLM Catalog and Bookshelf. Inclusion and exclusion CriteriaThe articles published in English language focusing human subject only were considered. Criteria followed include recent 12.5-year studies reported from five different geographic regions of Asia. Studies who had significantly explained the role of any sub-genotype of HPV in head and neck cancer. While, studies contradicting above mentioned inclusion criteria were considered ineligible and excluded. Detailed inclusion and exclusion criteria are mentioned in Studies Selection By Specific approach overall, Principal author and third co-author shortlisted n = 300 abstracts from NCBI databases, including n = 236 duplicate and older than Jan-2009 were excluded for further analysis. From above mentioned 300 citations, only 64 full text articles were found. But, Due to irrelevance with inclusion criteria 40 full text articles were excluded. However, 24 principal studies were focussed and critically analyzed Data Retrieval and Risk MeasuresTwo co-investigators belonging from another country focused on data review and validation in collaboration with principal author for each included study. Country of study, first author, year of publication, type/site of lesion, number of cases included. Specific HPV type and overall prevalence of HPV in head and neck cancer infection was also studied. Prevalence estimation was done as total number of patient positive for specific HPV-subtype divided by total number of HNSCC patients. The accuracy of data search was counter checked by a second researcher, Further, Omissions; errors were resolved by sharing it with another co-investigator from another territory. Statistical AnalysisStatistical analysis was done by using Revman 5.30, Prisma and Microsoft Excel 2010 multiple tools. Characteristics of Meta-AnalysisMeta-analysis concentrating number of included studies from a country, patient selection, mean age, method followed, and relative outcomes as described in  from 24 Based on purely two objective based search strategies including comprehensive and specific quality data retrieval approaches. overall 56,302 search results, 10,999 were reported from south Asia, 2,346 from middle East, 1,710 from central Asia, 1,229 from East Asia and only 17 search results from western Asia were found from recent eleven year published sources . Our speReflecting 24 principal studies, overall (9 %) prevalence of HPV was recorded in South Asia, 5.04 % in South East Asia,4.93 % East Asia, 2.21 % in west Asia, 0.32% from a bilateral Pak-Chinese study and no relevant updated patients’ data was found from central Asian continent regarding HNSCC. From comparative point of regional HPV prevalence, highest prevalence of HPV was noted in south Asia, south East Asia and very less in central and west parts of Asian continent respectively .HPV-genotype Specific PrevalenceOverall highest prevalence (10.08%) of HPV sub-genotype-16 was recorded in Asia among 3, 710 enrolled cases including 2,201 males, 1,149 females and 360 cases of unknown gender. While multiple HPV genotype prevalence was 5.5 % (204 cases), HPV-18 (2.12%), HPV-16 and 18 co-infection (1.51%) and 1.3 % cases were not known for any type specific HPV-genotype following whole Asian continent. Lowest percentage of HPV sub-genotypes 68, 72, 57, 39 were recorded respectively . Assessment of risk bias and clinical heterogeneity2 = 1.14, P< 0.00001, I2 = 87 %) was found between HPV positive HNSCCs and type specific HPV-16 led HNSCCs in Asian continent with an overall Odd ratio = 3. 41.  with an Odd ratio of = 14.57  with an Odd ratio = 0.47 . Greater heterogeneity in methodological aspect of included studies was also observed. Due to variable genotype testing methods including, PCR primers, ELIZA kits, ISH protocols and diversity in detection of HPV sub-genotypes followed by each individual study  was observed in overall 798 HPV positive cases in comparison to 48 non-determined HPV genotype case groups  of HPV-16 and India in HPV-31(0.61%), . South East AsiaHPV was (5.04 %) prevalent in south East Asia. However, 3.72 % multiple HPV genotypes were only reported from Singapore and overall HPV-16 was (1.24%) prevalent in South East Asia . East AsiaIn total 1,033 (27.84%) cases reported from east Asia HPV was found in 183 (4.93%) cases including (3.10%) HPV-16, 0.37% HPV-18, 0.03% HPV-33, HPV-39, HPV-58, HPV-66 and HPV-72 respectively. While 0.62 % cases were affected with multiple HPV genotypes. Taiwan was on top reporting (0.6%) prevalence of HPV-18 and in Japan HPV-35 was (0.08%) prevalent .West AsiaIn western Asia 2.21% prevalence of HPV was estimated. Similarly, HPV-16 and HPV-18 genotypes were found most prevalent. Equal prevalence of HPV-16 was obtained from both Egypt and Turkey . Un-Categorized groupA collaborative study conducted by Mujtaba et al., (2018) enrolled 506 HNSCC patients both from china and Pakistan. HPV was prevalent in 12 cases (0.32%). Inclusion of Mujtaba et al., (2018) in a distinct category was done to highlight recent progress in collaborative research culture as well .Central AsiaUnfortunately, as per criteria set forth, not a single study from central Asian territories were found including Turkmenistan, Kazakhstan, Kyrgyzstan, Uzbekistan and Tajikistan. First time our review critically analyzed the available literature covering the whole Asian continent and reported 21.5% prevalence of HPV associated HNSCCs with clear heterogeneity insights. While prior to current study HPV association in HNSCCs was considered in the range of 12.8%-59.9 %, including HPV-35, HPV-33, HPV-31, HPV-18 and HPV-16 genotypes only. . However, our review was a collaborative research effort to minimize cancer research gap in Asian continent and focussed prevalence of more than fifteen HPV sub-genotypes. Similar large scale regional and worldwide studies covering whole Asia reported (33%) HPV prevalence in HNC-subsite  among Asians, 16% in European and 16. 1% North American populations respectively  In 2014 another review reported by Abogunrin S et al focusing European population estimated 40 % prevalence of HPV in head and neck carcinomas. We accept exact prevalence of HPV associated HNSCCs among Asian population is still debateable and our study has certain limitations including non-availability of homogenise reported studies from Asian sub-continents especially central Asia, western Asia and even from south and south east Asia demand large scale collaborative research culture to standardize HPV led HNSCCs aetiology. Beside very potential outcomes, our review has certain limitations including a significant level of heterogeneity in comprised studies, Publication year, variable number of patients, specimen type and HPV detection methods. Similarly, the possibility of confounder cannot be ignoring, because some studies evaluated more then one type of HPV sub-genotype. while an included study detected HPV-16 genotype only as well. In conclusion, highest priority should be given to initiate homogeneity cancer research programs among Asian countries especially; Afghanistan, Iraq, Nepal and Yemen to assess the tumour positivity rates of HPV in HNSCCs. While in countries like Pakistan, India, Bangladesh, Thailand, North Korea, Iran, Japan and Turkey more collaborative research is needed to standardize prevalence of HPV associated HNSCCs across Asian Continent.Nil. PCR, Polymerase chain reaction; ISH, in-situ-hybridizations; ELIZA, Enzyme linked immunosorbent assay; HPV, human papilloma virus; HNC, head and neck cancer; CNS, Central Nervous System.


INK4a is a surrogate sensitive marker of HPV infection in PC.In Brazil, penile cancer (PC) is not uncommon. The highest incidence of PC is in the North and Northeast of the country. In addition to phimosis, the Human Papillomavirus (HPV) and Epstein-Baar Virus (EBV) infections are also related as risk factors for PC. The overexpression of p16INK4a overexpression and HPV infection status with EBV infection in a series of PC patients from the Amazon region.To correlate p16® HPV-Screening assay. p16INK4a expression was evaluated by immunohistochemistry using the automated Ventana® BenchMark Ultra.Tumor tissues from 47 PC cases were analyzed for the presence of HPV and EBV DNA by PCR. All PC patients were diagnosed between 2013 and 2018 at a public reference cancer center hospital in Manaus, Amazonas—Brazil. HPV was genotyped using E7 HPV16/HPV18 type-specific real-time PCR and the PapilloCheckINK4a was only investigated in 26 samples. The p16INK4a overexpression was observed exclusively in HPV 16 positive cases and four HPV negative cases. In the survival analysis, the follow-up time was 35.4 months/patient. The mortality rate during the follow up time was 38%.The mean age of patients at the time of diagnosis was 57.4 years ±SD 17.8 ranging from 20 to 90 years old. Most of the patients (64%) came from rural areas of the Amazonas State. Thirty patients had phimosis (64%). Among the patients with phimosis, 43% (13/30) underwent circumcision, three during childhood and 10 in adulthood. 60% of the patients were smokers or ex-smokers. HPV infection was observed in 45% (21/47) of cases. HPV16 was detected in 13 patients (61%). Other HPV types detected were HPV 6, 11, 42, 51, 53, 68 and 44/55. EBV infection was observed in 30% (14/47) of the patients with PC. Co-infection with HPV and EBV was observed in 28% (6/21) cases. p16INK4a positivity presented a high correlation to HPV 16 DNA detection, reinforcing its use as a surrogate marker for HPV-driven cancers. Infection with EBV was quite frequent and its role in epithelial penile oncogenesis needs to be demonstrated.p16 The occurrence of Penile Cancer (PC) varies worldwide. In developed countries, PC has a low incidence, corresponding to 0.3–1% of malignant neoplasms in men. In some developing countries, the incidence of PC may be much higher than the global average incidence . AccordiPC is a multifactorial disease and the risk factors and/or favorable conditions to develop PC are not fully established. Phimosis and smegma accumulation are observed in more than 80% of the patients with PC associated with chronic inflammation process ,7. OtherINK4a due to the lack of negative feedback loop between pRb and p16 protein . The p16INK4a overexpression was observed in the eight HPV 16 positive cases and in four HPV-. Other clinical factors were not significantly associated with HPV infection and p16INK4a overexpression. HPV infection and p16INK4a overexpression were also related to some histological subtypes, HPV infection being positive in the basaloid subtypes (45%) and negative in usual subtypes (81%) ; p = 0.026]. Notably, of the eight nonsmoker’s patients with p16INK4a overexpression, six had HPV 16 genotypes and the remaining two were negative for HPV. Among the four smoker’s patients with p16INK4a overexpression, two were HPV16 and two negative for HPV. HPV+ patients with PC had poorly differentiated carcinomas (Grade III) compared to HPV- patients with PC .Association of p16es (81%) . RegardiINK4a+ vs p16INK4a-, HPV+ vs HPV-, EBV+ vs EBV- and HPV/EBV co-infection vs no infection. Infection status of the deceased and survival patients is shown in log rank = 0.753), HPV infection (Plog rank = 0.979), EBV infection (Plog rank = 0.106) and HPV/EBV co-infection (Plog rank = 0.318) . Survival analysis was performed by stratification of the patients into p16= 0.318) .P16 exp2 and has about 4 million inhabitants. Half of the population lives in the capital city, Manaus while the other half is distributed irregularly in the rural regions with low density population with very poor access to health services . Among men circumcised in adulthood, phimosis was strongly associated with development of invasive penile cancer, in concordance with the findings of Daling, et al. (2005) , but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.”If your commercial affiliation did play a role in your study, please state and explain this role within your updated Funding Statement.b. Please also provide an updated Competing Interests Statement declaring this commercial affiliation along with any other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products, etc.  http://journals.plos.org/plosone/s/competing-interests) . If this adherence statement is not accurate and  there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.Within your Competing Interests Statement, please confirm that this commercial affiliation does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to  PLOS ONE policies on sharing data and materials.” . The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: YesReviewer #2: No**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: No**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: The authors present tumor tissue analyzes from 47 patients with penile cancer. Samples were analyzed for the presence of HPV and EBV DNA by PCR. In addition p16 INK4a expression was evaluated by immunohistochemistry. The results roughly agree with those in the world literature. In the second sentence of the introduction the authors state: In Brazil, PC accounts for approximately 2.1% of all tumors in men being the highest incidence reported in the world . In the cited article, Brazil appears in the first place in the ranking of Latin America being surpassed in the world by Romania and Uganda. The authors presented a survival curve showing a better prognosis for Ebv- patients when compared to Ebv +. I would like they comment on why this result.Reviewer #2: The present study is about penile cancer and oncogenic viruses HPV and EBV and their relationship with clinical and pathological characteristics. The work is important because penile carcinoma is an uncommon neoplasm, although in some regions of the world, such as Brazil, its incidence is higher, and because of the importance of exploring another possible etiological or risk factor, that is, EBV. HPV in penile cancer has been recognized in almost 50% of the cases. In contrast, the presence and biological and clinical relevance of EBV in penile cancer have not been sufficiently studied. However, it is necessary to review the scope of the findings and analyze the concomitant presence of both viruses and the clinical and pathological characteristics of the patients, in order to define the possible relationship of EBV in penile cancer. In this sense, it is necessary to consider the following observations.Title“HIGH PREVALENCE OF HPV WITH OVEREXPRESSION OF p16 INK4A PROTEIN AND CO-INFECTION WITH EBV IN PENILE CANCER – A SERIES OF CASES FROM BRAZIL AMAZON”. The title suggests that the authors found a higher prevalence of HPV than the one reported worldwide and that there is a concomitant presence of EBV infection in HPV positive cases. However, the data obtained does not reflect this. I suggest that the title should be modified to reflect in the best way the scope of the study and the results obtained.AbstractLine 27. It reads “Epstein Baar”; it should read “Epstein-Barr”.Line 57. It reads “Con-infection”; it should read “co-infection”.The conclusion states that “p16 INK4a positivity presented a high correlation to HPV 16 DNA detection, reinforcing its use as a surrogate marker for HPV-driven cancers.” This is not a novel finding. Thus, it is necessary to rewrite the conclusion in the abstract and the text after analyzing the group of concomitant HPV and EBV infection and EBV alone.IntroductionLine 56-58. It is necessary to update the references about epidemiological data of penile carcinoma, since the only reference is from 2010, and there are recent works on this issue.Line 69-70. Concerning HPV prevalence in penile carcinoma, it is necessary to complement and or compare the most recent data worldwide .Line 80-86. It is important to describe the oncogenic role of EBV in cancer, as currently known, and the cell types affected by such viruses. The relationship between EBV and HPV in carcinogenesis is described in various papers; one of them is a review by Guidry and Scott (doi:10.1016/j.virusres.2016.11.002.). It is necessary to expand the references about the oncogenic role of EBV in epithelial carcinogenesis.Line 87-88. It is necessary to describe in a better way the rationale or the relevance of the work, emphasizing the study of EBV and HPV, and the few studies specifically in penile carcinoma.Materials and MethodsLine 112-113. Specify the size of the b-globin product.Line 126. What is the reason to do specific E7 HPV 16 and 18? The results and discussion about this detection are not mentioned. Besides, the genotyping by papillocheck test was used. The rationale to detect E7 is not indicated.Line 171. It is necessary to indicate why only 21/47 samples were analyzed.ResultsTables 1 and 2 could be merged.Line 210-211. In patients with EBV and HPV co-infection, the relationship with p16 overexpression should be described.Table 3. Include the information about the expression of p16.Line 215-216. It would be important to evaluate the presence of HPV newly  in the positive cases of p16, which were initially identified as negative for HPV DNA.Line 219-220. Smoking and HPV presence are relatively excluding factors, at least in HNCSS. The relationship between overexpression of p16 and smoking was identified; however, it was not so with the presence of HPV. The analysis was made with all genotypes identified (low and high risk). What is the relationship between smoking and high-risk HPV presence?Line 223-228. It is necessary to describe the survival analysis of the group with co-infection of HPV and EBV since the analysis was only made individually, and an important issue (since the title of the study) is the co-infection of EBV and HPV. The result should be discussed.Table 4. This table could be simplified by removing the percentages (leaving the frequencies), and adding the EBV presence in the header row and respective analysis.DiscussionLine 251. The metastasis analysis should be extended. This issue has been addressed in head and neck carcinomas HPV negative versus positive, and also in nasopharyngeal carcinomas EBV positive, as well as prognosis factors associated.doi.org/10.1186/s12879-019-4696-6), reporting that at least 50% of men under 45 years have HPV. It is important to extend the discussion about the characteristics of penile cancer in young men and contrast the results with other reports.Line 252-253. The result about HPV in young men contrasts with a recent article , and this is not described in the discussion.Line 279-285. The relationship between EBV and HPV should be expanded. Although the relation between EBV and HPV in penile cancer is incipient, the relationship is described in another HPV-related cancer. Several articles have described the association between expression of p16 and EBV in other neoplasms (Doi: 10.1002/hed.24258. doi.org/10.1186/s12879-019-4696-6), and in contrast with the findings in other regions (DOI: 10.1002/jmv.20703).Line 289-290. The absence of HPV 18 in penile carcinoma is consistent with other works. (Line 295. Describe more broadly the possible mechanisms for the synergistic effect of HPV 6 and EBV.Line 302-303. What other genotypes (different to HPV 16) were present in the p16 positives cases?Line 304. Change the capital letters of the author's name cited.Line 313, Figure 2. The correlation between p16 overexpression and survival has been addressed in other neoplasms. The authors should review the impact of the clinical stage on survival. Did you consider the local and advanced stages for survival analysis?Finally, the authors should discuss the limitations of the study. For example, the number of p16 samples analyzed, if the size (3-5 mm) of samples analyzed was adequate for the detection of the viruses, p16, and pathological characteristics.One issue not mentioned is the presence of HPV without relation to penile carcinogenesis. Therefore, it is important to describe the p16 overexpression as a subrogate biomarker of carcinogenesis induced by high-risk HPV. The analysis of EBV dependent and independent of HPV should be extended and, consequently, the discussion.**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  19 Mar 2020Reply to reviewersReviewer #1:The authors present tumor tissue analyzes from 47 patients with penile cancer. Samples were analyzed for the presence of HPV and EBV DNA by PCR. In addition, p16 INK4a expression was evaluated by immunohistochemistry. The results roughly agree with those in the world literature. In the second sentence of the introduction the authors state: In Brazil, PC accounts for approximately 2.1% of all tumors in men being the highest incidence reported in the world . In the cited article, Brazil appears in the first place in the ranking of Latin America being surpassed in the world by Romania and Uganda. We agree and have corrected in the texts. (Line 57-58)The authors presented a survival curve showing a better prognosis for Ebv- patients when compared to Ebv +. I would like they comment on why this result.We agree with the reviewer that there is a trend due to the sudden drop of the survival curve. However, the comparison showed no difference (Plog rank = 0.106).Reply to reviewersReviewer #2: The present study is about penile cancer and oncogenic viruses HPV and EBV and their relationship with clinical and pathological characteristics. The work is important because penile carcinoma is an uncommon neoplasm, although in some regions of the world, such as Brazil, its incidence is higher, and because of the importance of exploring another possible etiological or risk factor, that is, EBV. HPV in penile cancer has been recognized in almost 50% of the cases. In contrast, the presence and biological and clinical relevance of EBV in penile cancer have not been sufficiently studied. However, it is necessary to review the scope of the findings and analyze the concomitant presence of both viruses and the clinical and pathological characteristics of the patients, in order to define the possible relationship of EBV in penile cancer. In this sense, it is necessary to consider the following observations.Title“HIGH PREVALENCE OF HPV WITH OVEREXPRESSION OF p16 INK4A PROTEIN AND CO-INFECTION WITH EBV IN PENILE CANCER – A SERIES OF CASES FROM BRAZIL AMAZON”. The title suggests that the authors found a higher prevalence of HPV than the one reported worldwide and that there is a concomitant presence of EBV infection in HPV positive cases. However, the data obtained does not reflect this. I suggest that the title should be modified to reflect in the best way the scope of the study and the results obtained.We agree and have rewritten the title.PRESENCE OF HPV WITH OVEREXPRESSION OF p16 INK4A PROTEIN AND EBV INFECTION IN PENILE CANCER – A SERIES OF CASES FROM BRAZIL AMAZON AbstractLine 27. It reads “Epstein Baar”; it should read “Epstein-Barr”.We have corrected in the texts. (Line 29)Line 57. It reads “Con-infection”; it should read “co-infection”.We have corrected in the texts. (Line 51-52)The conclusion states that “p16 INK4a positivity presented a high correlation to HPV 16 DNA detection, reinforcing its use as a surrogate marker for HPV-driven cancers.” This is not a novel finding. Thus, it is necessary to rewrite the conclusion in the abstract and the text after analyzing the group of concomitant HPV and EBV infection and EBV alone.We totally agree and have brought the necessary changes. (Line 51-52)IntroductionLine 56-58. It is necessary to update the references about epidemiological data of penile carcinoma, since the only reference is from 2010, and there are recent works on this issue.We have brought the necessary changes. (Line 55-57)Line 69-70. Concerning HPV prevalence in penile carcinoma, it is necessary to complement and or compare the most recent data worldwide . We have brought the necessary changes. (Line 69-71)Line 80-86. It is important to describe the oncogenic role of EBV in cancer, as currently known, and the cell types affected by such viruses. The relationship between EBV and HPV in carcinogenesis is described in various papers; one of them is a review by Guidry and Scott (doi:10.1016/j.virusres.2016.11.002.). It is necessary to expand the references about the oncogenic role of EBV in epithelial carcinogenesis.We have corrected accordingly. (Line 81-88)Line 87-88. It is necessary to describe in a better way the rationale or the relevance of the work, emphasizing the study of EBV and HPV, and the few studies specifically in penile carcinoma.We totally agree and have brought the necessary changes. (Line 89-90)Materials and MethodsLine 112-113. Specify the size of the b-globin product.We have provided in the text. (Line 115-117)Line 126. What is the reason to do specific E7 HPV 16 and 18? The results and discussion about this detection are not mentioned. Besides, the genotyping by PapilloCheck test was used. The rationale to detect E7 is not indicated.ReplyAs PapilloCheck is a very expensive test, we have chosen to primarily screen the presence of HPV followed by typing specifically for HPV16 and HPV18. All of the samples that were negative for HPV16 and HPV18 were screen by PapilloCheck test to reduce the cost of typing.Line 171. It is necessary to indicate why only 21/47 samples were analyzed.ReplyWe believe that there is misunderstanding here. We did already explain in the text. 21 samples were not available for pre-analytical analysis due to poor quality keeping of the samples.ResultsTables 1 and 2 could be merged.We do agree but merging both tables 1 and 2 will be heavy and confusing.Line 210-211. In patients with EBV and HPV co-infection, the relationship with p16 overexpression should be described.We have provided in the text. (Line 223-224)Table 3. Include the information about the expression of p16.ReplyAs we did for only 26 samples, we did not include in the Table 3 to avoid confusion, but we describe in text.Line 215-216. It would be important to evaluate the presence of HPV newly  in the positive cases of p16, which were initially identified as negative for HPV DNA.Reply The four samples that were positive for p16 and negative for HPV were again tested for the presence of HPV16 and HPV18 by real-time PCR and continued to be negative. Line 219-220. Smoking and HPV presence are relatively excluding factors, at least in HNCSS. The relationship between overexpression of p16 and smoking was identified; however, it was not so with the presence of HPV. The analysis was made with all genotypes identified (low and high risk). What is the relationship between smoking and high-risk HPV presence?ReplyWe have rewritten in the result section to avoid confusion. There was no relationship between smoking and high-risk HPV presence. As it can be seen that the driving force for the presence of p16 is mostly dependent on the presence of HPV and independent of the smoking status. (Line 232-238)Line 223-228. It is necessary to describe the survival analysis of the group with co-infection of HPV and EBV since the analysis was only made individually, and an important issue (since the title of the study) is the co-infection of EBV and HPV. The result should be discussed.Thank you for pointing this lack. We have performed the analysis and is shown in Figure 2D. The comparison showed no difference P log rank=0.318. We also included a S1 Table showing the infection status of the deceased and survived patients. (Line 240-241)Table 4. This table could be simplified by removing the percentages (leaving the frequencies) and adding the EBV presence in the header row and respective analysis.We have brought the necessary changes.DiscussionLine 251. The metastasis analysis should be extended. This issue has been addressed in head and neck carcinomas HPV negative versus positive, and also in nasopharyngeal carcinomas EBV positive, as well as prognosis factors associated.Reply As our study is only focused on penile cancer, we did not compare with other types of cancers as we believe that the developing mechanisms could be different. For this reason, we did not extend the discussion.doi.org/10.1186/s12879-019-4696-6), reporting that at least 50% of men under 45 years have HPV. It is important to extend the discussion about the characteristics of penile cancer in young men and contrast the results with other reports.Line 252-253. The result about HPV in young men contrasts with a recent article  were positive for HPV. Line 258. Change the capital letters in the author's name cited.We have corrected in the texts. (Line 259)Line 268. According to the data in Table 4, tumor grade III is associated with HPV presence. Improve the description of this finding and mention the concordance with previous works.We have added one more reference. (Line 292)Line 275-276. How could you explain the relationship between phimosis and overexpression of p16?We have provided in the discussion. (Line 300-312)doi.org/10.1016/j.ijrobp.2017.06.1473. doi.org/10.3389/fonc.2018.00113), and this is not described in the discussion.Line 279-285. The relationship between EBV and HPV should be expanded. Although the relation between EBV and HPV in penile cancer is incipient, the relationship is described in another HPV-related cancer. Several articles have described the association between expression of p16 and EBV in other neoplasms (Doi: 10.1002/hed.24258. Reply As cited previously (Answer Line 252). We have focus mainly on penile cancer. Considering that in other studies with penile cancer the HPV and EBV status were not predictive of outcome and we believe that the developing mechanisms could be different for another cancer.doi.org/10.1186/s12879-019-4696-6), and in contrast with the findings in other regions (DOI: 10.1002/jmv.20703).Line 289-290. The absence of HPV 18 in penile carcinoma is consistent with other works. (We have included in the text. (Line 326-329)Line 295. Describe more broadly the possible mechanisms for the synergistic effect of HPV 6 and EBV.We included in the text. (Line 333)Line 302-303. What other genotypes (different to HPV 16) were present in the p16 positives cases?We have described in the result section. (Line 229-229)Line 304. Change the capital letters of the author's name cited.We have corrected in the texts. (Line 342)Line 313, Figure 2. The correlation between p16 overexpression and survival has been addressed in other neoplasms. The authors should review the impact of the clinical stage on survival. Did you consider the local and advanced stages for survival analysis?ReplyWe have included in the text. However, we did stratify the patients according to the local and advanced stages as our sample size is small. And stratification will further reduce the sample and will not have any power to detect any difference according to our statistician. (Line 350-351)Finally, the authors should discuss the limitations of the study. For example, the number of p16 samples analyzed, if the size (3-5 mm) of samples analyzed was adequate for the detection of the viruses, p16, and pathological characteristics.We have described in the discussion section. And we also described in the materials and methods section and Supporting Information (S2 PROTOCOL - Immunohistochemistry for p16INK4a).One issue not mentioned is the presence of HPV without relation to penile carcinogenesis. Therefore, it is important to describe the p16 overexpression as a surrogate biomarker of carcinogenesis induced by high-risk HPV. The analysis of EBV dependent and independent of HPV should be extended and, consequently, the discussion.We have described in the discussion section.Sincerely yours, Yours faithfully,Valquiria do Carmo Alves MartinsOn behalf of all authorsAttachmentresponse_to_reviewers_AlvesVCR.docxSubmitted filename: Click here for additional data file. 16 Apr 2020PRESENCE OF HPV WITH OVEREXPRESSION OF p16 INK4A PROTEIN AND EBV INFECTION IN PENILE CANCER – A SERIES OF CASES FROM BRAZIL AMAZONPONE-D-19-35033R1Dear Dr. Martins,We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact With kind regards,Marc O. Siegel, MDAcademic EditorPLOS ONEAdditional Editor Comments :Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #1: All comments have been addressedReviewer #2: All comments have been addressed**********2. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: Yes**********3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: YesReviewer #2: Yes**********4. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: YesReviewer #2: Yes**********5. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes**********6. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: The authors made the changes that I requested. The manuscript deserves to be published due to the rarity of the tumor studied. In addition, it is important to have a sample of the population of Amazonas in northern Brazil. Mainly because it includes minority groups such as indigenous people.Reviewer #2: The authors have corrected and incorporated most of the previous suggestions and they have answered the questions. However, it is still necessary to correct some edition errors.Line 29. It reads “Epstein Baar”; it should read “Epstein-Barr”Lines 251-259 and page 13. The authors should check and make sure that the section and order of the footnotes of the figures are correct and complete.**********what does this mean?). If published, this will include your full peer review and any attached files.7. PLOS authors have the option to publish the peer review history of their article (If you choose “no”, your identity will remain anonymous but your review may still be made public.Do you want your identity to be public for this peer review? 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Background: Cervical cancer (CC) is the fourth most commonly diagnosed cancer among women. Ghana is a low-middle- income country with annual diagnosed cases of 3,151 and 2,119 deaths. The high prevalence rate of cervical cancer in Ghana is mainly due to ineffective preventive measures and insufficient knowledge about the disease. Therefore, our objective was to evaluate the level of knowledge and awareness of cervical cancer and attitude toward human papillomavirus and its vaccine among Ghanaians.Methods: This descriptive cross-sectional survey on the awareness of cervical cancer and attitude toward human papillomavirus and its vaccine was carried out from March 2019 to February 2020. SPSS v. 23.0 was used in the data analysis. The participants' demographic characteristics, knowledge of cervical carcinoma, human papillomavirus vaccine and HPV, and the likelihood to be vaccinated were represented as percentages and frequencies. The difference between males and females was assessed using the chi-square test. The logistic regression analysis was used to evaluate the relationship of possible related indicators with the willingness to receive the HPV vaccine. A p < 0.05 was considered statistically significant.Results: A total of 1,376 participants were involved in the final analysis. Among the 1,376 participants involved in this survey, 1,240 participants (90.1%) representing 456 males (33.1%) and 784 females (57.0%) were aware of the terminology “cervical cancer” with a significant p = 0.001. When stratified by gender, women had significantly greater knowledge, compared to men in terms of “cervical cancer being common in middle age (35–50) females” . When stratified by gender, women had significantly greater knowledge of human papillomavirus  and the human papillomavirus vaccine  compared to men.Conclusion: Majority of the respondents had poor knowledge regarding cervical cancer risk factors, symptoms, HPV, and its vaccine. Hence, this indicates a wakeup call for government to increase the awareness and knowledge level via the media and health professionals. Carcinoma of the cervix (CC) is the fourth most commonly diagnosed cancer among women with an annual new registered case of 569,847 and 311,365 deaths worldwide . Human pn = Z2P(1 – P)/d2; where, n = sample size; Z = z statistic for a level of confidence. For the level of confidence of 95%, which is conventional, the Z-value is 1.96. P = expected prevalence or proportion , and d = precision ”  a Ghanaian resident, either male or female, (ii) must be 18 years and above, (iii) not deaf and dumb, and (iv) women with no history of HPV vaccination. The target population of men and women mostly resided in either Accra, Kumasi, or Takoradi. These three cities were chosen due to their population density and the availability of cervical cancer screening programs. The questionnaires were designed after a comprehensive review of literature from past studies and then approved by experts –29. The = 0.05)” . The calP = 0.46 , consideThe selection of group and the designing of our questionnaire was based on  Theory oTo aid the respondents answer the questions easily and quickly, the questions covered in the questionnaires, was categorized into sociodemographic, knowledge on cervical cancer, knowledge of HPV vaccine and HPV, the willingness to receive the HPV vaccination themselves and also having their children vaccinated, the rationale for not being willing to be vaccinated and the acceptability to pay for the human papillomavirus vaccination by themselves and interview quality evaluation. The cervical cancer section was subcategorized into (a) knowledge about cervical cancer, (b) knowledge about cervical cancer symptoms, and (c) knowledge about risk factors of cervical cancer. Knowledge of cervical cancer was evaluated if a participant responded that they were aware of cervical carcinoma by stating that one has heard or knows about cervical cancer. The participant's knowledge regarding the risk factors  and symptoms  of cervical carcinoma was evaluated. A 30-point score was used to evaluate cervical cancer knowledge. Five points were allocated to every sub-section of knowledge; hence participants were required to range between 0 and 30 scores. One point was allocated to each true response, and zero points to the incorrect response. Participants who responded only “Yes” to the questionnaire's first statement, “Do you know about cervical cancer?” were assigned a knowledge score. Participants' level of knowledge while calculating the knowledge score was categorized using Bloom's cut off point . ParticiHPV awareness was evaluated with the phrase, “Have you heard of HPV?” Participants who responded “yes” to this statement were regarded to have knowledge about HPV. The knowledge on HPV vaccine was evaluated in the same manner. Some previous studies have reported these questions . Other rp < 0.05 was considered statistically significant.SPSS v. 23.0 was used in the data analysis. The participants' demographic characteristics, knowledge of cervical carcinoma, human papillomavirus vaccine and HPV, and likelihood to be vaccinated were represented by percentages and frequencies. The difference between males and females was assessed using the chi-square test. The logistic regression analysis was used to evaluate the relationship of possible related indicators with the willingness to receive the HPV vaccine. Indicators in the univariate model were integrated into a multivariate logistic regression, in which confidence intervals of 95% and the adjusted odds ratio were estimated. A stratified assessment was conducted to determine whether gender affected the factors correlated with the willingness to be vaccinated. A Of the total 1,500 survey respondents, 124 answered the questionnaires with inconsistent and incomplete responses. After eliminating the inconsistent and incomplete questionnaires, the remaining questionnaires were analyzed and the total response rate was 91.73%. A total of 1,376 participants were involved in the final analysis. p ≤ 0.001). These participants were examined further to test their knowledge on some risk factors and symptoms of cervical cancer, as presented in p ≤ 0.001),” “lower abdominal pain ” and “vaginal discharge with foul smell ” as being the dominant cervical cancer symptoms. Likewise, a high proportion among the responses regarding the risk factors “Human papillomavirus infection ” and “unprotected sexual practices ” was noticed. Our survey respondents were ranked in each sub-category according to their level of knowledge in cervical cancer epidemiology, symptoms, and risk factors. In general, 75.3% of the respondents had good knowledge of cervical carcinoma epidemiology; however, it was accompanied by moderate knowledge in terms of cervical cancer risk factors (63.8%) and symptoms (61.6%) per the Bloom's cut-off point for accessing knowledge level. Respondents were asked regarding sources of information on cervical carcinoma and the main sources were social media/radio/television , nurses/doctors , newspapers/magazines , and relatives/family .Among the 1,376 participants involved in this survey, 1,240 participants (90.1%) representing 456 males (33.1%) and 784 females (57.0%) were aware of the terminology “cervical cancer.” When stratified by gender, women had significantly greater knowledge, compared to men in terms of “cervical cancer being common in middle age (35–50) females”  have “heard of HPV,” and only 36.9% have “heard of the HPV vaccine.” When stratified by gender, women had significantly greater knowledge of human papillomavirus  and the human papillomavirus vaccine  compared to men.As presented in N = 414) of the respondents were aware that HPV infection is transmitted through sexual contact  and 75.1% of the respondents were aware that “the persistent infection of high-risk HPV is the leading cause of cervical cancer and other HPV cancer types” with a significant p < 0.001. Furthermore, among respondents with knowledge of the HPV vaccine, only 55.9%  knew that cervical cancer could be prevented with the HPV vaccine. Additionally, only 21.7%  knew that “HPV vaccination is needed before first sexual intercourse.”Among the respondents who have heard of HPV, 59.8%  respondents were willing to have the HPV vaccination. Likewise, women had significantly greater willingness, compared to men . A total of 83.9% of women were willing to vaccinate their current and future children. Furthermore, the major reasons for respondents refusing to undertake the HPV vaccinations were “worrying about the safety of vaccine (30.2%),” “the HPV vaccine has not been widely accepted (13.1%),” “worrying about the price (13.1%),” and “worry about the effectiveness (12.7%).” Participants who said no to the payment for the HPV vaccine suggested that, WHO (70.4%) and the government (60.5%) should ensure the free supply of the HPV vaccine.In general, 80.5% , respondents who are Christians , college/graduate students , respondents who had their first sex at age above18 years , respondents with monthly income 2,000–3,999 Ghana cedis , respondent with knowledge about CC , respondent who have heard of HPV  and heard of HPV vaccine  were more willing to receive the HPV vaccinations. Hence, a strong association between these variables and a respondent willingness to be vaccinated. Advancement in understanding cervical carcinoma has been effective in acknowledging its preventive nature . It is fOur study findings showed that majority (90.1%) of the participants were knowledgeable of the term cervical cancer which is higher when compared with other similar studies in developing countries such as Pakistan, Ethiopia, and Zambia and where the percentage of participants knowledgeable of the term cervical cancer were 51.3, 76.8, and 36.8%, respectively , 37, 38.Among these risk factors, “human papillomavirus infection” and “unprotected sexual practices” were correctly and highly identified as cervical cancer risk factors. This finding is lower when compared to past studies conducted in South Africa, Bhutan, Malaysia, and Ukraine –42. ThisRegarding awareness of cervical cancer symptoms, respondents were aware of symptoms such as “vaginal discharge with a foul smell,” “bleeding after sexual intercourse,” and “bleeding in-between period” . Our results indicate that much effort is needed to educate the general public, especially women of cervical cancer symptoms, since failure to recognize these symptoms or late presentation can results in delaying medical care, resulting in poor prognosis and higher death rates.There is no doubt that basic knowledge is essential in encouraging women to patronage preventive actions. This is in line with the intrapersonal level regression findings for SEM, where basic knowledge concerning cervical cancer was the key predictor of attitude . CommuniReligious beliefs were believed to hinder screening and vaccine uptake. The findings contradict this hypothesis in that there was no influence of religion on screening choices, but rather religion had a good impact on the acceptability of vaccination. This is contradictory to other nations where religion was observed to hinder uptake of vaccination , 44. AboPrevious studies on HPV awareness with a large sample size reported that the percentage of women knowledgeable of HPV ranged from 15.0 to 44.9% –48. We nEven though there was a higher willingness of participants to accept the vaccination, the primary complaints among participants not willing to accept the vaccination were how safe the vaccine is, in addition to the acceptability of it worldwide and the price of the vaccine. This finding is similar to a study by , where pIn our survey, most Ghanaians claim to be affiliate with the Christian religion. Hence improvement in the vaccine coverage can be increased with clergy's the support since the majority of these churches are mostly arraigned of refusing western medication due to biblical and moral values. Again, regular visitation to Church must be taken to motivate church members to participate in vaccination programs and further ensure that accurate information on cervical cancer is disseminated during their health talk. There is a need for the general public to be educated to understand the significance of the vaccination in addition to risk factors, symptoms, and screening of cervical carcinoma due to low knowledge and awareness highlighted in our study. Furthermore, community-based programs and interventional strategies must be targeted at both women and men because men were an influential element in the acceptability of the HPV vaccination by women.Some limitations need to be highlighted. First, study participation was voluntary. Hence, most of the participants may have been those who demonstrated greater interest in the subject. Secondly, the study was limited to three cities in Ghana; therefore, the entire population cannot be generalized to our findings. Thus, the participants in the study constitute a representative sample. Also, different results will be obtained from new studies targeting rural communities and different residential areas. Thirdly, our survey centered on acceptability instead of uptake of the HPV vaccine; thus, it is uncertain if the intentions of participants to be vaccinated would turn into actions. Lastly, due to different educational backgrounds, some participants may not have completely grasped the questions, contributing to possible bias.Taking into account the findings of this survey, certain policies can be implemented. First of all, it is important to ensure that screening facilities for cervical carcinoma are accessible in all health centers. Because of low awareness, probably providing such services in all health centers will result in an effective outreach between women and healthcare providers who may visit the health center for certain health purposes. In regards to the HPV vaccines, the higher willingness among respondents to accept the vaccine was a good sign. Since reproductive age in Ghana starts very early, it is, however, essential to begin vaccinations early in adolescence. HPV vaccines can be added to the normal vaccination program as an effective-cost solution, or “community-based vaccine drives” can be launched via the Ministry of Health. In principle, advancement in acceptance of vaccines, along with changes in behavior, would have a huge influence on Cervical Cancer Prevention in Ghana.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Zhengzhou University and Henan Provincial People's Hospital. The patients/participants provided their written informed consent to participate in this study.ED wrote and presented the original draft. LZ and QH were involved in data curation and visualization. CE, CA, GA, ES, and FF were involved in methodology, software, analysis, review and editing. KS was involved in supervision.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In the multivariate analysis, attending a health sciences university, using social networks ≤2 h a day, a history of STI, having heard about HPV and HPV vaccine previously resulted as predictors of higher knowledge scores. Having heard about HPV previously also predicted a high attitude score, together with a perceived economic status as good. Having Italian and healthcare worker parents, being employed, and following a specific diet, instead, predicted lower attitude score. Conclusions: Poor knowledge and good attitudes were found among undergraduates about HPV. In order to increase HPV vaccine compliance and the counselling skills of future healthcare workers, the improvement of training on HPV is needed.Background: Human Papillomavirus (HPV) is a common sexually transmitted infection (STI), representing the main cause of genital warts and cervical cancer. This cross-sectional study evaluated knowledge and attitudes about HPV infection, related diseases, and prevention and propensity towards HPV vaccine among undergraduate students. Methods: An online and written survey about HPV and its prevention, targeted to young adults of both genders, was addressed to students attending health sciences and other schools at Universities of Genoa and Bari. Results: The overall median knowledge and attitude scores were 56.3% (25–75  Human papillomavirus (HPV) infection is recognized as the most common STI worldwide ,2. HPV iData acquired in recent years confirm that HPV vaccines and screening are the most effective prevention tools ; in partDespite this prevention opportunity, the coverage rate is still suboptimal in Italy, as in other countries, due to HPV vaccination uptake barriers, such as inadequate knowledge of HPV infection and related diseases, vaccination safety concerns, organizational aspects of HPV vaccine campaigns, and difficulties in vaccine schedule completion for subjects and providers . In ordeA cross-sectional multicenter survey about HPV and its prevention, targeted to young adults of both genders, was carried out from May 2017 to December 2018. The study population included females who retain the right to free-charge vaccination, males who can benefit from the vaccine in co-payment regimens, and subjects at risk, like those who are HIV-positive and men who have sex with men. Recruitment of the study participants took place at the University of Genoa , University of Bari , and the San Martino Hospital in Genoa. In particular, subjects were recruited among students attending healthcare profession schools  who are required to periodically undergo a medical examination at occupational health surveillance outpatient clinics and who are attending academic schools including public health and prevention subjects in the first and second academic years. The study staff enrolled the students at the outpatient clinic and on the occasion of academic lessons. The sample size was calculated considering the number of subjects belonging to the target study population, the at-risk subjects, and healthcare personnel, the available evidence about the HPV vaccine acceptability fixing the confidence interval at 95%, a margin of error (+/−) of 2.5%, and adding a quota of 5%, in consideration of the possible drop-outs and missed answers.Ad hoc anonymous questionnaires addressed to young adults were developed. They were self-administered using the Google Drive platform that automatically populates and saves digital responses into a secure Microsoft Excel database protecting participant confidentiality throughout the surveying process. A consent page reporting the study aims and objectives, the participant’s right to the refusal or the possibility to terminate the participation in the study at any time and without disadvantages was created.Participants could also fill two written informed consent and questionnaires characterized by the same structure of those administered online. The first questionnaire was set in two sections: the first one investigated the country of parent’s birth, level of parent’s education, parent’s occupation, and, for the participant, demographics, level of education, occupation, economic status, professed religion, healthy behavior, such as following a specific nutritional regimen (diet) and sport practice, sexual behaviors and orientation, use of the Internet and social networks, the sources used for seeking information on sexually transmitted diseases (STDs), including HPV, and remembering about vaccines received during childhood. The first section also included a 10-point Likert scale ranking the interest to receive an HPV vaccine. The second section included 13 questions on the knowledge on HPV infection, related diseases, and vaccine. The second questionnaire assessed their attitude using nine statements with a five-point Likert scale for each one . It also included a 10-point Likert scale on how much the participant was interested to receive HPV vaccine after reading some information on HPV infection, related diseases, and vaccine included at the beginning of the second questionnaire (self-learning). Based on the participants’ responses, the knowledge, attitude, and intention scores were calculated. The ‘knowledge’ score summarizes the percentage of correct answers the participants gave among the knowledge questions. For each knowledge statement, one point was given for a correct answer  and zero points if they selected a wrong answer or “Do not know”. The total points were added for every participant and a percentage was calculated (number of correct answers/number of knowledge statements × 100). The higher the knowledge score, the more knowledgeable the participant is regarding HPV infection, its related diseases, and prevention. The attitude score was obtained by calculating the average of the participants’ responses to the statements on a five-point Likert scale. The median of the total points was calculated for every participant obtaining an attitude score ranging from 1.0 to 5.0. The closer the attitude score to 5, the more positive the participant’s attitudes. The “intention” score reflects the propensity toward the HPV vaccine. The “intention” score was estimated both at the beginning and at the end of the survey, when the information about HPV infection and vaccination had been given. The score is a scale from 1 to 10, where 10 reflects the highest propensity toward the HPV vaccine.p-value less than 0.05 was considered significant throughout the study. Multivariate logistic regression analysis was performed to identify the predictors of having high knowledge score or positive attitude score towards HPV vaccination. Only covariates that showed a significance level of p-value < 0.1 in the univariate analysis were included in the multivariable regression model, using a backward stepwise algorithm. Given the high number of potential independent variables, a backward stepwise algorithm was used to identify the best-fitting subset of variables to use in the final regression model. In particular, Akaike’s Information Criterion (AIC) was used to assess the models’ fit and the model with the lowest AIC was selected for the multivariable analysis. β-coefficients (95% C.I.) and p-values were estimated.Statistical analysis was performed by means of JMP software , version 13 and Microsoft Excel, version 2016 after generating data from the written questionnaires and Google Drive . Median and 25–75 percentiles for continuous variables, frequencies, and percentages for categorical variables were calculated. The possible association of baseline characteristics of young adults with knowledge and attitude scores was tested through univariable logistic regression. A In complying with the highest ethical standards, participants were informed that their participation was entirely voluntary and that they could withdraw at any moment. All data obtained through their participation was kept strictly confidential among the research team. In addition, an informed consent was obtained after explaining the nature of the study and its possible consequences of it. The study protocol was approved by the Liguria Regional Ethics Committee (P.R. 162REG2017) for the study coordination center.p = 19–21), 65.2% were female and 95.9% were Italian. A total of 97.1% declared to be students and only 2.9% were employed. A total of 24.5% of subjects had a graduate parent and 10.4% had at least one parent who was a health care operator. A total of 53.3% of the subjects consider their own economic status as good. As regards lifestyle habits, 23.1% and 56.6% of participants follow a specific diet and practice sports, respectively. Furthermore, 65% and 49.6% of young adults surfed the Internet and used the social networks up to 2 h a day, respectively. Among sexual habits, 61.8% of subjects had a partner at the time of the survey and 83.8% used contraceptive methods, the most reported of which was condom use (61.7% of cases). Furthermore, 97.2% of participants were heterosexual. The median age of sexual debut and number of partners in the last year were 17 (25–75 p = 16–18) and 1 (25–75 p = 1–1), respectively.A total of 680 young adults returned the self-administered questionnaires, giving a response rate of 100%. A total of 80.4% of subjects had heard about HPV vaccine before the survey, in particular from a family member (43.7% of cases), Internet (24% of cases), teachers (25.1% of cases), and LHAs informative material (23.6% of cases) .p = 40–68.8).The overall median knowledge score was 56.3%  and that using condoms reduces the risk of HPV infection (86.2%) . Only 40p < 0.0001), using social networks up to 2 h a day (p = 0.0215), history of sexual transmitted infection and of HPV-related lesions , and having heard about HPV before the survey (p = 0.0035). Furthermore, family members and mass media as source of information about HPV are significantly related to worse knowledge scores . Gynecologists, instead, are reported as a source of information by young adults with significantly higher knowledge scores (p = 0.0014).p = 4–5). Only 49.7% of participants agree or strongly agree that during the own life he/she will have high probability to be exposed to HPV infections , who are not employed (p = 0.0211), who reported a good economic status (p = 0.0031), who do not follow a specific diet (p = 0.0004), who use social network up to 2 h a day (p = 0.0115), those without immunodeficiencies (p = 0.0381), and those who heard about HPV before the survey (p < 0.0001). As regards the source of information about HPV vaccine, subjects who reported teachers, LHAs informative material, pediatricians/general practitioners, had significantly higher attitude scores .p = 8–10).The median propensity score before and after the educational intervention was stable and high as 9  country such as Italy, where a dynamicity in the objectives and targets of HPV vaccination by public health since its introduction in 2007 was observed. This study was performed not only in undergraduates attending health sciences schools, but also in other university students.Young adults are a category at risk of sexually transmitted HPV infection. Since HPV has a causative role in serious and frequent diseases, such as cancers and genital warts, respectively, interventions to prevent low and high-risk types of HPV infections are urgently warranted; indeed, vaccinating both men and women against HPV is crucial to protect against HPV-related cancers and other diseases.Recent international recommendation on HPV vaccination have included additional age classes, not only adolescents of both genders (aged 11–12 years), but also females 13–26 years-old who have not been previously vaccinated or who have not completed the vaccine series, and males aged 13–21 years and 22–26 years with special conditions or who want to protect themselves from the disease ,18. The An evaluation of what young adults know about the threat of HPV and believe about HPV prevention can offer possible solutions to remedy the underutilization of the HPV vaccine in a population at high risk for contracting this preventable infection and to explore innovative strategies. The findings are, therefore, relevant at the light of better understanding and comparing educational needs and attitudes toward HPV infection and prevention in one of the HPV vaccine targets ,21,22. Fp < 0.0001). Results worthy of highlighting are that more than 93% affirmed that HPV can be implicated in developing serious disease but only 49.7% consider themselves at risk of exposure to HPV. These results are comparable with those described by Villanueva et al. who recently investigated knowledge, attitudes, and intentions towards HPV among nursing students in Spain [Our findings highlight, on one side, insufficient knowledge of undergraduate students on HPV infection and HPV- related diseases, on the other side, a substantial positive attitude toward the vaccine. Gaps on HPV knowledge were detected in previous studies enrolling study population similar to our study population for demographic characteristics ,24,25,26in Spain . The abop = 0.0491), who mainly come from developing countries. A possible explanation could be a better propensity by the foreign families towards Italian healthcare services, including prevention. As regards lifestyles, the young who follow specific nutritional regimen had significantly lower attitude score (p = 0.0044), confirmed by multivariate analysis (p < 0.0001), this could be explained by the fact that those who engage in specific behaviors oriented around ‘the natural’ is often hesitant or refuse vaccines [p = 16–18), with a median of lifetime sexual partners of 2 (25–75 p = 1–4). These findings are substantially comparable with the observations obtained in other European countries [p = 0.0440). This observation could be linked to the previous contact of affected subjects with the healthcare system which could have favored the acquisition of knowledge on this topic.Among young adults characteristics, parents’ nationality, educational qualification, and employment were investigated in relation to knowledge and attitude scores. The knowledge score resulted higher, although not statistically significant, in young adults with healthcare worker parents, while the attitude score was higher for subjects with parents who are employed in other sectors. This observation could be linked to the well-known largely suboptimal compliance of healthcare workers to vaccines ,29. Furtvaccines . Surprisountries ,25. Consp = 0.0072 and p < 0.001). In particular, family members, Internet, teachers, and LHAs’ informative material were the most frequently reported sources of information. Surfing the web and the use of social networks were also investigated, showing that using social network ≤2 h/day is among the predictors of better knowledge on HPV compared to higher use (p = 0.0141). This finding suggests that social networks can also disseminate misleading messages on HPV. Nevertheless, the increasing pervasiveness of social media, such as Facebook, as powerful communication channels means that they can potentially be used to effectively reach young people. Therefore, public health should better communicate messages through existing networks and engage in on-going dialogue with users [Before the educational moment, subjects were asked to declare if they have heard about HPV previously. Our findings revealed that a high percentage of young (80%) already knew this infection, which is well up rates reported in other published research ,32,33 anth users ,35,36.Our study also deepened attitudes regarding the favorite sources of information about HPV of participating subjects, finding that talking about HPV with teachers and trusted doctor is considered very useful by young adults, while only 51.8% and 39.9% of participants believe that parents’ and partner’s opinions are essential to decide to get vaccinated against HPV. These answers confirm the role of physicians and teachers recognized by young adults in spreading health information including sensitive topics such as STIs. Of note, the majority of participants (83.92%) agree or strongly agree to make compulsory HPV vaccine for boys and girls before the sexual debut and for at risk subjects. This is of interest in countries such as Italy where a recent law introduced the compulsory of some vaccines, excluding HPV .p = 8–10) and remained stable after the educational session. A recent meta-analysis that assessed the effectiveness of interventions targeting HPV vaccine initiation and completion among children, adolescents, and young adults aged 9–26 years support behavioral and informational interventions, including education , educational websites tailored to baseline knowledge, and brochures/factsheets, for HPV vaccine initiation and behavioral interventions for completion [In order to evaluate the efficacy of educational intervention in implementing the propensity of young adults toward HPV vaccine, we estimated it through a score before and after the administration of a written text summarizing the available evidences on HPV infection, related diseases and prevention. The score resulted very high (median = 9, 25–75 mpletion . Considempletion . This evThe study limits are the nature of self-reported data collected from the participants, which may be compromised by the respondents’ memory of experiences of interest. Furthermore, since northern and southern regions were involved in the enrollments, the representativeness of young adults living in the Central Italian regions is lacking. Despite these limitations, this survey obtained a very high response rate, demonstrating the strong interest in HPV topic. As regards education, the self-learning session could be improved by focus groups and other interactive methods. Nevertheless, academic public health teaching includes HPV burden and prevention among treated themes.The results of the current study demonstrates that Italian undergraduates show suboptimal knowledge on HPV and good attitudes. Since they represent both the target of HPV vaccine and future healthcare workers, the implementation of training about HPV infection, its related diseases, and prevention tools are needed to support the important role they play in the prevention of STIs, some of which are related to the occurrence of cancer. Universities represent a privileged setting to spread information about HPV to the target audience and young adults recognize teachers together with trusted doctors as the favorite source of information. Improving students’ knowledge may have favorable implications in increasing vaccine coverage rates.