HPV persistence is a key determinant of cervical carcinogenesis. The influence of postpartum on HPV clearance has been debated. This study aimed to assess HPV clearance in later pregnancy and postpartum among HIV-positive and negative women.We conducted a follow-up study with 151 HPV-positive women coinfected with HIV, in 2007–2010. After baseline assessment, all women were retested for HPV infection using PCR in later pregnancy and after delivery. Multivariable logistic regressions assessed the putative association of covariates with HPV status in between each one of the successive visits.Seventy-one women (47%) have eliminated HPV between the baseline visit and their second or third visits. HIV-positive women took a significantly longer time (7.0 ± 3.8 months) to clear HPV, compared to those not infected by HIV (5.9 ± 3.0 months). HPV clearance was significantly more likely to take place after delivery than during pregnancy (84.5% x 15.5%).Both HIV-positive and negative women presented a significant reduction in HPV infection during the postpartum period. HIV-positive status was found to be associated with a longer period of time to clear HPV infection in pregnant women. Human papillomavirus (HPV) is highly prevalent in non-vaccinated sexually active women worldwide, even among those presenting normal cytology . Most HPHPV clearance is more frequent in the first six months after prime infection, with rates of 50-70% per follow-up year ,13. AdeqHIV-positive women have a higher risk of acquiring new HPV infections and a lower chance of clearing them compared to women not infected by HIV -21. MarkChanges in immunity and other biological parameters (e.g. changes in the levels of different hormones) during pregnancy and postpartum may modulate the natural history of HPV infection. Some recent studies did not observe differences in HPV status over time, during pregnancy -25. MostThe dynamics of HPV infection during pregnancy is not well established and information remains scarce and controversial. Few studies have studied HPV clearance and persistence during and after pregnancy, and just one of them has prospectively evaluated HPV infection in HIV-positive women. In this study, we aimed to evaluate HPV clearance in the postpartum period of both HIV-positive and negative women.A prospective follow-up study was carried out between January 2007 and January 2010, in Ribeirão Preto, São Paulo state, Brazil. Pregnant women were selected consecutively from the Prenatal Outpatient Clinic of the Infectious Diseases Unit, Obstetrics and Gynecology Department of the University Hospital, Medical School of Ribeirão Preto, University of São Paulo. This is a tertiary service, which follows-up with women previously diagnosed with HIV or HPV infection at primary units, selected from a large catchment population mainly composed of women from middle and low socioeconomic strata. Women were evaluated according to their HIV status and/or HPV-related lesion. HPV infection type was classified as clinical (in case of warts), subclinical (in case that colposcopic lesions were made evident), or HPV-positive (if only PCR-positive).Inclusion criteria were as follows: 1) be in the 1st half of pregnancy; 2) be positive for HPV, as defined by a PCR exam; 3) be an adult ; and 4) have read and signed the informed consent form.Cervicovaginal samples  were collected from all women and tested for HPV by Polymerase Chain Reaction (PCR). Women who tested positive for HPV were re-evaluated at two subsequent visits: at the 2nd half of pregnancy and after delivery.The study protocol was approved by the Ethics Review Board of the Ribeirao Preto’s Medical School Hospital – Sao Paulo University, and all women voluntarily signed informed consent before enrolment. All patients followed antenatal care routine of the service and no procedure was altered for those women enrolled in the study, except for the three PCR exams performed in each one of the visits .Cervicovaginal samples were stored at -80°C until DNA extraction, which was performed by QIAamp® DNA Mini Kit . Consensus primers GP5+ / GP6+ were used to identify HPV positivity, as previously described . After tSample size was calculated with the help of Graphpad StatMate® . Assuming a 15% differential clearance over time (from early pregnancy up to postpartum), it would be necessary to include at least 99 patients, considering an 80% power and an alpha of 5%.HPV clearance was defined as having at least one negative result after a confirmed positive one. A negative test detected in the 2nd visit (followed by a negative one in the 3rd visit) was defined as “clearance”, taking place between the 1st and the 2nd visit (i.e. clearance during pregnancy). Women with positive tests in the first and second visits, followed by a negative test in the 3rd visit, were defined as “clearance” occurring between the 2nd and the 3rd visits (i.e. clearance during the postpartum period).Persistent infection was defined for the sake of our study as “the consecutive detection of at least two positive HPV tests between the second and the third visit” . When a negative result appeared in between two positive tests (i.e. between the baseline and the third visit), the intermediate result was defined as a false negative, in agreement with previous studies and their respective criteria ,35. DuraStatistical analysis was carried out with the help of EpiInfo 3.5.3  and SAS 9.0 . Paired t-tests  and chi-square test (or Fisher Exact test for table cells with less than 5 events) were used for univariate analysis. Multiple log-binomial regression models were used, as the outcome was binary; procedure PROC GENMOD was applied for model adjustment. Multivariable analyses were controlled for participants’ age, smoking/non-smoking, mode of delivery, HIV status, nature of HPV infection , and HPV type (dichotomous variable: high vs. low risk).One hundred and fifty-one HPV-positive women were enrolled and followed-up with, of which 54 were HIV-positive and 97 were HIV-negative Figure . Mean geOverall genotype prevalences were as follows (in descending order of frequency): 37.1% (HPV 6 / 11), 23.8% (HPV 18), 13.2% (HPV 16), 4.0% (HPV 31), and 4.0% (HPV 33). None of these genotypes were identified in 43 samples (28.5%). The socio-demographic characteristics, as well as clinical and laboratory data did not significantly differ between these women and those form whom HPV infection was typed.3 and 44% of them present viral loads above 10,000 copies/mL.More than half of the HIV-positive women had their condition diagnosed less than a year ago (28/54). More than 60% of these women had CD4+ counts above 350 cells/mmOverall, clearance rate was 47% (71/151). The groups among whom HPV had persisted or cleared did not differ in median age , nor in gestational age at their 1st visit . HIV-positive and negative women did not significantly differ regarding HPV clearance rates ; but HIV-positive women took a significantly longer time (7.0 ± 3.8 months) to clear HPV, compared to those not infected by HIV (5.9 ± 3.0 months).Univariate analyses are summarised in Table Clearance rate was slightly higher in women with LR-HPV than those with HR-HPV infection, but such difference was not found to be statistically significant (20/39 (51.3%) vs. 22/56 (39.3%); p = 0.25).3 cleared HPV during follow-up (20/26) and only 4 women with less than 1,000 copies/mL had a persistent HPV infection over the follow-up period (4/11).Almost half of the women living with HIV infection cleared HPV infection during follow-up (26/54). Lower HIV viral load and higher CD4+ cell counts were found to be associated with HPV clearance. More than 75% of HIV-women with CD4+ count over 350 cells/mmIn multivariable analysis, non-smoker women had a two-fold higher chance to clear HPV  compared with smokers. Additional data are presented in Table HPV clearance was made evident between the 2nd and the 3rd (postpartum) visits in 84.5% of women who cleared HPV infection (60/71), compared to 15.5% during the 1st and 2nd visits  (11/71). Such difference was statistically significant for women, irrespectively of their HIV status, as well as when analyses were stratified by HIV status . More than 90% of our patients have used this therapy during pregnancy, which might influence our results. A recent study has demonstrated that highly active antiretroviral therapy may increase the clearance of some oncogenic HPV types . These fOurs is the first study to assess HPV clearance among HIV-positive women during pregnancy and postpartum. Minkoff et al.  compared3. A South-African study found that low CD4+ count was associated with a higher HPV infection incidence, but no association with clearance was made evident by it. Clearance was found to be exclusively associated with HIV viral load [In the HER Study (HIV Epidemiology Research), which included more than 500 HIV-positive women, higher CD4+ cell counts were found to be associated with a higher HPV clearance . Rowhaniral load . Furtherral load . In the We further analysed the database in order to assess a putative linear relationship between successive categories of CD4+ counts  and HPV clearance (data not shown). Unfortunately, we did not observe any gradient, either because it does not exist or because of our small sample size (beta error).The study assessed HPV types using a modest set of primers and HPV type-persistence was not assessed. Further studies, profiting from a comprehensive variety of HPV primers and a follow-up of HPV-types incidence/clearance over time is sorely needed in order to complement and validate our findings.In longitudinal studies, clearance rates and median infection duration might be underestimated due to left-censoring of infections present at the beginning of the study and right-censoring of infections that have not been cleared until the end of follow-up. The current study had a relatively short follow-up and intervals between visits, which were limited to pregnancy and post-partum. Such a short period of time  might compromise our ability to assess HPV evaluation. Women might have cleared their infection between visits, and it is not possible to specify the precise moment during which clearance may take place. The association between HPV and HIV coinfection might be underestimated in which case a longer follow-up period would be necessary to properly assess it over time.Chlamydia trachomatis. Therefore, some unmeasured confounding may have affected the adjusted risk ratios.Our findings should not be generalised to other groups of pregnant women, due to its small sample size, short follow-up time, and the fact that our study enrolled women from a tertiary referral care unit. Other sexually transmitted infections were not investigated such as HPV pathophysiology is especially complex due to the impossibility to fully differentiate persistent infections from those which might have occurred during the interval of two consecutive visits. Besides such caveat, a negative HPV test may not represent the full elimination of the virus, since latent infection may remain elusive from the perspective of both clinical and laboratory assessments. According to Schiffman et al. , HPV reaThe current study aimed to better assess some controversial aspects of HPV’s natural history. Postpartum period appears to be a period of significant decline of HPV infection, among both HIV-negative and positive women. The mode of delivery does not seem to influence this decline. A better understanding of HPV dynamics may help to identify women at higher risk of developing HPV-related lesions during antenatal care, contributing to prevention of cervical cancer, especially among HIV-positive women, among whom such cancers tend to be especially aggressive and harmful.HPV: Human papillomavirus; HIV: Human immunodeficiency virus; PCR: Polymerase chain reaction; LR-HPV: Low-risk HPV; HR-HPV: High-risk HPV.The authors declare that they have no competing interests.EMJ and SMQ conceived and designed the project, and analysed data. PPSM participated in data collection. GD and FIB provided guidance on this project. RTS and AYY carried out the PCR analysis. RAAM contributed to the data analysis and in the review process. All authors have been involved in drafting or revising the manuscript and have approved its final version.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/564/prepub


Infection with HIV is known to increase the risk of cervical cancer. In addition, evidence suggests that concurrent infection with multiple human papillomavirus (HPV) genotypes increases the risk of cervical dysplasia more than infection with a single HPV genotype. However, the impact of the combination of HIV coinfection and presence of multiple concurrent HPV infections on the risk of cervical dysplasia is uncertain. We compared the results of HPV testing and Pap smears between HIV-infected and HIV-uninfected young women to assess the cumulative impact of these two conditions. We found that both HIV and the presence of multiple concurrent HPV infections are associated with increased risk of associated Pap smear abnormality and that the impact of these two risk factors may be additive. Coinfection with HIV has a significant impact on the natural history of high-risk human papillomavirus (HR-HPV) infections, the causative agents of cervical cancer. Women with HIV are more likely to be infected with HPV, and more likely to harbor multiple concurrent HPV infections  . While mMultiple concurrent HPV infections have been associated with an increased risk of persistent HPV infection  and of dCervical cancer is the number one cancer cause of years of life lost in the developing world  where ovBetween October 2013 and March 2015, we conducted a longitudinal study of 50 HIV-infected and 50 HIV-uninfected young, sexually active, South African women. Cohort enrollment occurred sequentially until the goal of 50 participants in each group was met. Study participants were recruited through the Youth Centre in Masiphumelele and the Hannan Crusaid Clinic in Gugulethu, townships in the Cape Town area of South Africa. The Youth Centre in Masiphumelele serves the general adolescent population of the township, while the Hannan Crusaid Clinic specifically serves the HIV-infected population of Gugulethu. Demographic and behavioral variables of our cohort are presented in Serial HPV DNA testing, utilizing self-collected specimens, was conducted approximately every six months for all participants. In addition, all study participants underwent baseline Pap smear testing. Most study participants underwent additional Pap testing during the follow-up period. Subsequent Pap testing  was conducted at varying intervals depending on HIV status and previous Pap result as per the guidelines of the Western Cape Province. Only the enrollment HPV and Pap test results are used in this analysis. HIV status was confirmed upon enrollment and HIV-uninfected participants underwent HIV testing at every study visit. Women with a history of HPV vaccination or cervical surgery were excluded.Roche Diagnostics Linear Array HPV Test was used for all HPV genotyping. This kit identifies 37 HPV genotypes including all oncogenic “high-risk” HPV genotypes (HR-HPV) as designated by the International Agency for Research on Cancer . These 1χ2 tests for independence were used to compare groups, and Pearson and Spearman correlations were used to examine bivariate associations. All analyses were performed using IBM SPSS 22.0.Pearson p = 0.15).Preliminary descriptive cross-sectional data from the initial 85 participants in this cohort have been previously published . Among op < 0.001) and multiple concurrent HR-HPV infections . The average number of HPV infections was 2.92 for the HIV-infected group compared to 0.90 for the HIV-uninfected group (p < 0.001). Likewise, the average number of HR-HPV infections was greater among those with HIV . HIV-infected participants had a greater proportion of abnormal Pap smears at baseline (24% versus 12%), although this difference was not statistically significant (p = 0.12).Overall, HIV-infected women had a much greater burden of HPV infection. HIV-infected participants had greater proportions of multiple concurrent HPV infections . When eliminating those women without an HPV infection and comparing HIV-infected women with multiple infections to those with a single HPV infection, the difference is still substantial (33% versus 20%) although not statistically significant (p = 0.43). Thus, there may be an additive effect in which the combination of HIV infection and the presence of multiple concurrent HPV infections increases the association with cervical dysplasia greater than either risk factor alone.Among HIV-infected women only, those with two or more HPV infections were more likely to have an associated Pap abnormality compared to those with zero or one HPV infection . Among HIV-uninfected women, the difference is greater  though not statistically significant due to the small size of this subset (p = 0.18).3 . Forty-four percent were receiving antiretroviral (ARV) medications at the time of testing. The average CD4 count for those on ARV medications was 482 and for those not on ARV medications was 547 (p = 0.37). CD4 count was not found to be significantly associated with abnormal Pap test (p = 0.21) or total HPV infections (p = 0.07), although higher CD4 counts were associated with fewer HR-HPV infections . No significant relationship between ARV medications and the total number of HPV infections (p = 0.54) or the number of high-risk HPV infections (p = 0.77) was identified.Overall, our HIV-infected participants were not severely immune-compromised. Their average CD4 count was 518/mmr = 0.23, p = 0.019), number of HR-HPV infections , and baseline Pap test abnormality . There were no relationships observed between HPV infections or Pap abnormality and lifetime smoking, lifetime number of sexual partners, number of sexual partners in the last 6 months, and current use of condoms, birth control pills, or birth control injections .Our bivariate analyses identified positive associations between age and number of HPV infections (Pearson Our results demonstrate a large burden of HPV among our study population with a notably high prevalence of multiple concurrent infections. This is consistent with previous data from South Africa . We confIt is well established that HPV causes cervical cancer . It is lLikewise, HIV infection is known to increase the risk of cervical dysplasia . Data frThe impact of multiple concurrent HPV infections on the duration of infection is uncertain. Some prior research has found no impact of multiple concurrent infections on HPV persistence , 21. In This study has several limitations. The generalizability of the findings presented may be limited due to the specific geographical area from which the study cohort was drawn. Despite the numerous statistically significant findings, the relatively small sample size may have restricted the identification of important differences between groups and subgroups. Likewise, multivariate analyses examining differences between HIV-infected and HIV-uninfected participants while controlling for behavioral and demographic variables were not feasible due to the sample size. Lastly, because of the relative immune competency of our HIV-infected group and sample size limitations, study findings cannot be correlated with the extent of immunosuppression among HIV-infected participants.In our cohort, Pap smear abnormalities were identified twice as frequently among HIV-infected women as among their HIV-uninfected counterparts. In addition, among all women in the cohort, having multiple concurrent HPV infections was associated with twice the likelihood of an associated Pap smear abnormality compared to having a single HPV infection. These risk factors may be additive given our finding that HIV-infected women with multiple concurrent HPV infections were more likely to have associated Pap smear abnormalities than HIV-infected women with a single HPV infection.


Results suggested that the best predictor for improvement of vaccination was the awareness level and health education. This indicates a need for an educational intervention to raise awareness, increase HPV vaccine uptake, and decrease the incidence of cervical cancer.Human Papillomavirus (HPV) vaccination decreases the risk for cervical cancer. However, the uptake of HPV vaccine remains low when compared with other recommended vaccines. This study evaluates the knowledge and attitudes towards HPV infection and vaccination, and the readiness for the uptake of HPV vaccine amongst female students attending Oakland University (OU) in Michigan, United States. This is a cross-sectional study targeting a randomized sample of a 1000 female OU students using an online questionnaire. The data were statistically analyzed using SPSS software. A total of 192 female students, with the mean age of 24 years completed the survey. The majority of participants had previous sexual experience with occasional use of contraceptives (78.1%), were non-smokers (92.7%), and non-alcohol drinkers (54.2%). The participants had a mean knowledge score of 53.0% with a standard error of 2.3% translating to a moderately informed population. The majority agreed that HPV is life threatening (79%), the vaccine prevents cervical cancer (62%), and that side effects would not deter them from vaccination (63%). Although two thirds (67%) believed that, based on sexual practices in the United States, female college students in Michigan have a higher chance of contracting HPV, about 50% did not believe they themselves were at risk. Higher knowledge correlated with increased recommendation for the vaccine (correlation-factor 0.20,  According to the Centers for Disease Control and Prevention (CDC), about 6 million newly diagnosed cases of HPV infections are reported every year. In fact, genital infection with HPV is the most common sexually transmitted infection (STI) . HPV typIt is well known that, cervical cancer can be prevented if herd immunity and screening are insured. Since the introduction of the Papanicalaou smear in the 1950s, the incidence and mortality from cervical cancer have decreased in the US . In addiThe primary objective of this study is to examine the knowledge and attitudes towards HPV infection and vaccination as well as the readiness for the uptake of the HPV vaccine amongst female college students. By exploring the barriers to vaccination, this study aims to develop realistic future educational interventions that would increase vaccination rates and decrease the incidence of the HPV infection and cervical cancer.A cross-sectional survey was performed targeting a randomized sample of 1000 female Oakland University students 18 years old and above. The survey instrument was an online self-administered anonymous questionnaire conducted using Google forms  provided the email addresses. The study invitation was an email that included an information sheet with the study aims and objectives along with the participant’s right to refuse or terminate their participation at any time and without penalty. By clicking on the link to the survey, the participants consented. The completion of the self-administered questionnaire was voluntary, anonymous, and confidential. The survey was available in English, the predominant language at Oakland University.The study design and questionnaire content were approved by Oakland University Institutional Review Board. The participants were informed that their participation is entirely voluntary and that they can omit questions they prefer not to answer. All responses amounting from the study were kept strictly confidential.Data analysis was performed by the biostatistician in the Department of Biomedical Sciences at OUWB School of Medicine, Michigan. Statistical analysis was performed using SPSS Statistics for Windows Version 21.0. .Out of the 1000 approached individuals, only 192 participants completed the survey. The participation rate was 19.2%. The average age was 24 years with a standard deviation of 6.9 years and a range of 19 to 54 years. Participants’ demographics are summarized in The main sources of information about HPV and the HPV vaccine were personal physicians, followed by the media, then family and friends. Educational lectures, the Internet, and other resources were conceived as minor sources of information.The majority of participants (73%) confirmed that HPV infections cause cervical cancer, while a minority (19%) thought that it causes ovarian cancer and the rest (8%) did not know. Although 52% knew that HPV is an STI that can cause genital warts, 73% of the participants thought that only women can be infected with HPV and manifest the symptoms. About two thirds of participants (65%) believed that all HPV infections are caused by one strain of the virus. In addition, 75% of the participants incorrectly answered that the HPV vaccine can only be acquired after the age of 18 years. Moreover, 71% believed that women can only contract the virus from a symptomatic sexual partner and 43% incorrectly believed that HPV infections lead to genital herpes. The rest of the results are exhibited in After calculations, the combined mean knowledge score was 53.0% with a narrow standard error of 2.3%. This translates that on the average each participant answered half of the knowledge questions correctly. Stratified by different demographic variables, those that were in a health related major had a significantly higher knowledge of HPV (61% ± 19%) than those that were in a non-health related major (50% ± 23%) . The average knowledge score of the undergraduates was 52% ± 23% while the average of the graduates was 58%±18%; however, this difference in means was not significant . In addition, the difference between the other variables such as smoking status, alcohol consumption, vaccination status, and whether the participant heard of HPV as not significant , see Two thirds (67%) of the participants believed that, based on the general sexual practices in the US, female college students in Michigan have a high chance of contracting an HPV infection; however, about 50% of the participants did not believe that they themselves were at a risk of contracting HPV. In addition, 67% of the participants considered recommending the vaccine to fellow female colleagues and 76% agreed that gynecologists and personal physicians should offer the vaccine to their patients. A majority of the participants agreed that the HPV infection is a serious and life threatening (79%), the vaccine prevents cervical cancer (62%), and that side effects from the vaccine would not deter them from vaccination (63%). However, only 39% considered the vaccine affordable and 33% considered the vaccine as a product produced by pharmaceuticals for non-lucrative reasons. All the participants’ responses to attitude statements are summarized in After completion of the survey and the educational material, the intention of receiving HPV was assessed for each participant on a scale of 1 to 10, with 1 being least likely and 10 being most likely. The mean intention score to take the HPV vaccine after fulfilling the survey was 6.51 with a standard deviation of 3.51 and a median of 7.00. Participants who were vaccinated already had a significantly higher average intention score (8.6) of recommending a wide coverage of HPV and more college students should take the vaccine when compared with non-vaccinated participants who had a lower average intention score (4.4) (p˂0.0001) to do so.Pearson Correlations relating knowledge and attitudes about HPV were calculated. Participants with higher knowledge about HPV considered recommending HPV vaccines to female college students, with a correlation factor was 0.20 (p = 0.005). In addition, participants with higher HPV knowledge significantly considered that gynecologists should recommend the vaccine to female patients. They also believed that HPV is a serious infection and they would recommend the vaccine to their friends. Moreover, they agreed that the side effects are reasonable and are, therefore, more willing to receive the vaccine. The results of these associations are highlighted in A multivariable analysis was conducted in this study assessing for knowledge and attitude. The results are highlighted in While previous studies in this field examined the medical efficacy of the HPV vaccine in preventing cervical cancer, this study explored the HPV infection and vaccination from a social and public health perspective. To achieve complete prevention of any preventable disease, public awareness and health literacy are essential. Even though HPV infections are the most common STIs , this stA national survey analysis revealed that the two most common reasons for parents refusing vaccination for their children were perceived low risk for HPV and institutional barriers . InteresThe major source of information about HPV, in this study, was personal physicians and gynecologists (71%). However, a recent systematic review of the literature showed that there is low knowledge about HPV infection and its relationship with non-cervical cancers/genital warts among health care professionals (HCP) . The HCPIt is important to explore the economic burden of HPV and cervical cancer. In fact, cervical cancer disproportionately affects women of socio-economically disadvantaged and ethnic minorities in the United States . Those t8 and in New Zealand were only 7% were vaccinated [It is encouraging to note that 46% of participants were already vaccinated before completion of the survey, which is significantly higher than similar studies conducted in Lebanon where 16.7% of participants were vaccinated ccinated . Furtherccinated . MoreoveThe study sample was chosen by convenience in this study and the targeted population was only female college students attending Oakland University in Rochester, Michigan. Therefore, generalizations from this study cannot be made, as this sample is not representative of the general population. A larger nationwide survey might offer more significant results. This study also focused only on female students and currently the vaccination is recommended for males as well. In brief, a more inclusive survey would offer more impactful information on the barriers to vaccination.This study tackled, in depth the knowledge, attitude, and intentions of female university students regarding HPV infections and vaccines in the aim of identifying areas and predictors of improvements. The knowledge about HPV was moderate, and the best predictor of improvement was the awareness and health education levels. Therefore, educational resources and activities, as well as awareness campaigns seem to be an inexpensive and effective way to improve disease knowledge, tolerance, and increase HPV vaccination rates. It would also be relevant to assess the current contribution of HCP and health care systems in the fight against HPV, assess knowledge and attitudes of adolescent males, and look for further sources of improvement.S1 Survey(DOCX)Click here for additional data file.


Targeted advertising using social networking sites (SNS) as a recruitment strategy in health research is in its infancy.The aim of this study was to determine the feasibility of targeted Facebook advertisements to increase recruitment of unvaccinated women into a human papillomavirus (HPV) vaccine effectiveness study.Between September 2011 and November 2013, females aged 18 to 25 years, residing in Victoria, Australia, were recruited through Facebook advertisements relating to general women’s health. From November 2013 to June 2015, targeted advertising campaigns were implemented to specifically recruit women who had not received the HPV vaccine. Consenting participants were invited to complete an online questionnaire and those who had ever had sexual intercourse were asked to provide a self-collected vaginal swab. The HPV vaccination status of participants was confirmed from the National HPV Vaccination Program Register (NHVPR).P<.001). A greater proportion of the total sample completed tertiary education and resided in inner regional Victoria, compared with National population census data (P<.001), but was otherwise representative of the general population.The campaign comprised 10 advertisements shown between September 2011 and June 2015 which generated 55,381,637 impressions, yielding 23,714 clicks, at an overall cost of AUD $22,078.85. A total of 919 participants were recruited. A greater proportion of unvaccinated women  were recruited into the study following targeted advertising, compared with those recruited  prior to showing the modified advertisement (Targeted Facebook advertising is a rapid and cost-effective way of recruiting young unvaccinated women into a HPV vaccine effectiveness study. Human papillomavirus (HPV) is the most common sexually transmitted viral infection worldwide. Approximately 80% of sexually active individuals will acquire an HPV infection during their lifetime; most within a few years following sexual debut . PersistIn 2007, Australia was the first country to implement a national government-funded HPV vaccination program using the quadrivalent HPV  vaccine Gardasil (4vHPV) -6. The vAlthough Internet social networking sites (SNS) have been in use for over a decade, the concept of targeted advertising as a recruitment strategy in health research is still in its infancy. Approximately 93% of Australians use Facebook, including 97% of 18 to 29 year olds . In addiThe VACCINE study is a cross-sectional survey in which Facebook was used to recruit participants . The objThe methods for this study have been published previously . The stuParticipants were recruited through advertisements published on Facebook. From September 2011 to November 2013, advertisements were set to randomly appear to Facebook users who were (1) female; (2) between the ages of 18 and 25 years; and (3) residing in Victoria, Australia.The advertisements contained a brief headline , a generic picture of young women and a brief caption . The advRespondents could click through to the secure VACCINE Study website to read more about the study and register an expression of interest (EOI). Potential participants were contacted and screened by telephone to assess their eligibility and willingness to comply with the study requirements.Participants who verbally consented to the study were invited to provide electronic consent and to complete a self-administered, password-protected questionnaire hosted by the online survey tool SurveyMonkey. The survey questions related to demographic characteristics, sexual history and knowledge, attitudes and practices regarding HPV, the HPV vaccine, and cervical cancer screening. Participants were also requested to provide their HPV vaccination status and written or electronic consent for their HPV vaccination history to be verified with the NHVPR.P value <.05 was considered statistically significant. Data were treated as missing if a question was skipped or “prefer not to answer” was selected.Descriptive statistical analyses were conducted using Stata 13.1 . The demographics of our cohort were compared with general population data sourced from the Australian Bureau of Statistics 2011 census data . SocioecParticipants who received all 3 doses of the HPV vaccine were considered “vaccinated”; those who had received 1 or 2 doses were considered “under-vaccinated” and women who never received the HPV vaccine were recorded as ”unvaccinated“.For the duration of the entire campaign (September 2011 to June 2015), 10 advertisements resulted in 55,381,637 impressions, reaching 984,159 people, and yielding 23,714 clicks, at an overall cost of AUD $22,078.85. This translated to an average cost of AUD $24.02 per participant. The general advertisements which were implemented from September 2011 to November 2013, made 35,906,205 impressions, yielding 15,304 clicks, with an overall cost of AUD $15,381,92. The average cost per click was AUD $1.01 with a click-through rate of 0.04% per impression. From November 2013 to June 2015, 19,475,432 impressions were made, yielding 8410 clicks, with an overall cost of AUD $6696.93. The average cost per click was AUD $0.80 .P<.001)  were unvaccinated. In contrast, only 19.3% (127/659) of the participants who completed the questionnaire prior to modification of the advertisements had never been vaccinated (P<.001) . There wP<.001)  .P<.001) and had completed tertiary education . Women living in inner regional areas were over-represented   . Compare P<.001) .Targeted Facebook advertising led to increased recruitment of young women who had not received the HPV vaccine, without employing other recruitment methods. The rationale behind over-recruiting unvaccinated women was to allow us to reliably measure any difference in the prevalence of high-risk HPV between unvaccinated and vaccinated women. We also show that recruiting through Facebook is cost-effective given that the cost per participant in this study was AUD $24.02.Evidence from previous studies has shown that targeted Facebook advertising is effective in recruiting participants into health research ,23,24. IP<.001); a larger sample size is required to determine whether this is meaningful.Our study sample compared well with the general population in age. The significantly greater proportion of women born outside of Australia recruited via targeted advertisements compared with those recruited through general advertisements is intuitive as overseas students are not eligible for the HPV vaccine. Although young women who were born in Australia and/or had completed tertiary education were over-represented in the total sample; these biases are common in population-based studies ,24,28. TThere is an inherent risk of introducing sampling bias when targeting Facebook advertising for specific characteristics. We found that our sample was reasonably representative of the general population, except for country of birth and education level. Another potential cause of bias associated with this recruitment method is snowball or chain-referral sampling, whereby users exposed to these advertisements share information about the study on their Facebook profile page with their friends, or relatives, who may then submit an EOI. We found that 78% heard about the study from the Facebook advertisements, whereas approximately 17% either read a post on their friend’s Facebook wall or were told by a friend to participate. These 17% referrals were constant pre and post changes to the advertisements. Given the small proportion who submitted an EOI without having seen the Facebook advertisements, we contend that this did not have a significant impact on our results.We have demonstrated the utility of paid, targeted Facebook advertising as a contemporary and effective recruitment method. The ability to specifically target individuals with particular characteristics by tailoring Facebook advertisements enables researchers to recruit specific groups of individuals of interest into health studies.


The development and licensing of a nonavalent human papillomavirus (HPV) vaccine has the potential to reduce morbidity and mortality from HPV-related cancers beyond that of first generation HPV vaccines. However, this benefit can only be realised if the offer of vaccination is accepted. Uptake of first generation HPV vaccines is not complete and shows huge global variation. In addition to practical and financial challenges to optimising coverage, behavioural issues explain a large proportion of the variance in vaccine receipt. This commentary draws on the findings of over a decade of behavioural science research seeking to understand uptake of first generation HPV vaccines, in order to anticipate challenges to implement the nonavalent HPV vaccine. Challenges include distrust of combination vaccines, uncertainty about long-term efficacy, distrust of a new and (perceived to be) untested vaccine, cost and uncertainty regarding interchanging doses of first generation and nonavalent vaccines and the appropriateness of revaccination. We use behavioural science theory and existing evaluations of interventions to increase uptake of vaccines to identify evidence-based approaches that can be implemented by vaccine stakeholders to address parents' concerns and maximise uptake of the nonavalent HPV vaccine. •The benefits of human papillomavirus (HPV) vaccines can only be realised if uptake is optimal.•Behavioural science can help anticipate challenges to uptake of new HPV vaccines.•Challenges include distrust of combination vaccines and distrust of new vaccines.•Cost and uncertainty about interchanging HPV vaccines may also affect uptake.•Approaches to increase uptake of new HPV vaccines are identified. The development and worldwide implementation of vaccines against HPV have the potential to substantially reduce the burden of HPV-related cancers. First generation HPV vaccines  offer protection against HPV types 16 and 18, which are known to cause up to 80% of HPV-related cancers (depending on cancer site) More recently, a vaccine protecting against nine types of HPV has been licensed for use in the European Union (EU) and United States of America  While the development of vaccines against HPV represents a tremendous scientific advance, the promise of reduced incidence of HPV-related cancers can only be realised if the offer of vaccination is accepted. However, uptake is sub-optimal in most countries and shows wide global variation. With few exceptions In addition to the practical and financial challenges to implementing vaccination programs and optimising coverage, behavioural issues have been shown to explain 40% of the variance in vaccine receipt 22.1Studies have identified parental concern that vaccines can damage children by overloading their immune systems 2.2et al.) suggest that these parents believe that vaccination should occur close to sexual debut to maximise the duration of protection after potential exposure to HPV. Concerns about duration of protection are not limited to HPV vaccines Uncertainty about the duration of protection afforded by first generation HPV vaccines has been a prevalent concern, due to the relatively recent development of the vaccines, and the scientific uncertainty about the actual duration of protection 2.3One online focus group study of parents of vaccinated and unvaccinated girls, conducted in the USA, identified concern about side-effects of the nonavalent vaccine Concerns about vaccine safety are not unique to HPV vaccines. However, the impact of such concerns on vaccine coverage should not be underestimated. Pre- and post-licensing surveillance data show that HPV vaccines are safe 33.1Economic modelling suggests that nonavalent vaccination would be more cost-effective than quadrivalent if the additional cost per dose did not exceed $13 3.2While the nonavalent vaccine is being introduced, parents whose children have had one or two doses of a first generation HPV vaccine may query whether it is possible to complete the series with the nonavalent one. In addition, parents whose children have completed the series with one of the first generation vaccines may see the benefits of the nonavalent vaccine and consider whether it is appropriate to revaccinate with the new vaccine. However, there have been no studies looking at the inter-changeability of HPV vaccines and there is only preliminary evidence that vaccination with the nonavalent vaccine is safe following series completion with the quadrivalent vaccine 4Where parents are given the option to choose between first generation and nonavalent vaccines, uptake may not fall, as parents with concerns can choose the more established first generation alternative. However, where choice of HPV vaccine is restricted by health insurers/health authorities, the vaccine offered may affect uptake. In such circumstances, vaccination stakeholders would benefit from the insights that behavioural science can offer about interventions for maximising uptake.The behavioural scientist's toolkit includes a number of theories that have informed research seeking to understand the psychosocial factors influencing HPV vaccine receipt, as well as to identify targets for interventions to increase uptake. Two key theories have been used often in this field: the theory of planned behaviour (TPB) There is evidence that some behavioural interventions are effective at increasing uptake of HPV vaccination Vaccination stakeholders may also consider addressing some of the concerns that parents may have about the nonavalent vaccine. Parents' potential concerns about the safety and efficacy of the nonavalent vaccine may be clarified by explaining what testing has been done and why efficacy is likely to be sustained. Long-term studies of cohorts who received the quadrivalent vaccine have not shown any reduction in immunity, suggesting that the nonavalent vaccine may also provide long-term protection 5Nonavalent HPV vaccines represent a new opportunity to prevent HPV-related cancers. Drawing on the evidence-base generated by behavioural science with regard to first generation HPV vaccines, vaccination stakeholders can anticipate parents' concerns and be prepared to address them. Modifying interventions that we know are effective at improving HPV vaccination uptake, so that they tackle concerns specific to the nonavalent vaccine, may help to maximise uptake.Cancer Research UK . The funder played no role in the writing of this current perspective report and in the decision to submit the article for publication.This work was supported by None declared.


Background. The effect of HPV infection status and ethnic differences on the prognosis of tongue squamous cell carcinoma in Xinjiang presents an interesting set of conditions that has yet to be studied. Methods. A comprehensive analysis of clinical data was undertaken for a cohort consisting of 63 patients with tongue squamous cell carcinoma recruited from three ethnic groups in Xinjiang. PCR was used for the detection of HPV16 and HPV18 infections. Kaplan-Meier survival analysis was used for analyzing survival outcome in addition to the assessment of other prognostic factors. Results. The overall infection rate for HPV was 28.6% (18/63); the 5-year survival rate among the HPV-positive patients was 47.8% and 30.3% for HPV-negative patients. The survival rate for HPV-positive patients who received radiotherapy and chemotherapy was better than for those who did not receive radiotherapy and chemotherapy. N staging and HPV infection were found to be two independent and significant prognostic factors. Conclusion. HPV-positive patients with tongue squamous cell carcinoma are more sensitive to chemotherapy. Higher N staging indicates poor prognosis. The incidence of head and neck cancer is ranked sixth amongst malignant tumors and the most common manifestation of this cancer is squamous cell carcinoma. Numerous studies show that human papilloma virus (HPV) plays an important role in the etiology of head and neck squamous cell carcinoma , 2. HPV 63 tongue squamous cell carcinoma cases were recruited from June 2004 to June 2013 from the First Affiliated Hospital of Xinjiang Medical University. The Ethical Committee of the hospital approved the study plan. Their TNM stage was declared according to guidelines of the International Union against Cancer (UICC) version 2002. The patients receiving surgical treatment were diagnosed by pathological slides of the tumors located on the base of the tongue and the patients with nonsurgical treatment were diagnosed by radiographic examination  and biopsy pathology. Human Papillomavirus (HPV) DNA detection was performed on paraffin-embedded tissues. The cohort consisted of 25 males and 38 females, aged 28 to 84 (median age 56 years). The ethnic composition of the patients was 19 Uighur, 10 Kazak, and 34 Han. 19 were smokers and 44 nonsmokers; 27 patients drink frequently and 36 did not. According to UICC/AJCC2002, 36 cases were in stage I, 12 in stage II, 7 in stage III, and 8 in stage IV; the pathological differentiation showed that 40 tumors were well differentiated, 23 moderately differentiated, and zero poorly differentiated.Treatments of patients included surgery alone (26 cases), preoperative induction chemotherapy plus surgery (3 cases), surgery plus adjuvant radiotherapy and chemotherapy (26 cases), radiotherapy (5 cases), and radiotherapy combined with chemotherapy (3 cases). The surgical approach was expanding lesion resection neck dissection; radiotherapy used three-dimensional conformal radiation therapy or intensity-modulated radiation therapy by external beam linear accelerator, 6MV-X line.μm thick slides were loaded into 1.5 mL centrifuge tubes for DNA extraction.Pathological slides were stained by H&E and diagnosed by two pathologists. 4 QIAamp DNA FFPE Tissue Kit (number 56404) was purchased from Qiagen Company, Germany, to extract tissue DNA. The primer sequences used were HPV16 ; HPV18 .2O was used as negative control. PCR amplification was performed using a temperature gradient and 20 μL reactions which consisted of 2× Premix Ex Taq™ 10 μL, Forward Primer 0.5 μL, Reverse Primer 0.5 μL, ddH2O 7 μL, and genomic DNA template 2 μL. HPV16 amplification parameters were 95°C for 3 min, 95°C for 30 s, an annealing temperature of 55°C for 30 s, 72°C for 30 s, 35 total cycles, and a final extension at 72°C for 5 min. HPV18 amplification parameters were 95°C for 3 min, 95°C for 30 s, an annealing temperature of 57°C for 30 s, 72°C for 30 s, 35 total cycles, and a final extension at 72°C 5 min.The genomic DNA was extracted from wax-embedded tissue and stored at −20°C. DNA from SiHa cells and HeLa cells was used as HPV16 and HPV18 positive controls and Hα = 0.05.In this study, overall survival (OS) was scored as the primary outcome. Death was used as the end point and Kaplan-Meier survival analysis was performed. Univariate analysis was applied to the patient's age, sex, ethnic group, gender, smoking, drinking, M stage, T stage, N stage, tumor differentiation, location, HPV status, and 5-year survival rate. Log-rank testing was also used in the analyses. The COX proportional regression model was used to evaluate possible prognostic factors. The significance level was set at In 63 patients with squamous cell carcinoma of the tongue, overall HPV infection rate was 28.6% (18/63). HPV16 infection rate was 23.8% (15/63); HPV18 infection rate was 7.9% (5/63); dual HPV16 and HPV18 infection was found in 2 cases (1 Uighur and 1 Han).The follow-up time varied from 8 to 87 months with a median follow-up time of 36 months. Five cases were lost (7.9%). The overall five-year survival rate was 35.6%.P < 0.05); the age, sex, ethnicity, smoking, drinking, tumor differentiation, and T stage showed no significant association with their prognosis (P > 0.05)  . (1) The Impact of HPV Infection on the 3- and 5-Year Survival Rate of Patients with/without Surgery. Whether or not the patients underwent surgery had no impact on the 3- and 5-year survival rate of HPV-positive or HPV-negative patients (P > 0.05) ( > 0.05) .(2) The Impact of HPV Infection on the 3- and 5-Year Survival Rate of Patients with/without Radiotherapy. Patients who had the radiation therapy had a better 3- and 5-year survival rate than those who did not receive radiotherapy (P < 0.05) ( < 0.05) .(3) The Impact of HPV Infection on the 3- and 5-Year Survival Rate of Patients with/without Chemotherapy. Patients who received chemotherapy had a better 3-year and 5-year survival rate than those who did not receive chemotherapy (P < 0.05) ( < 0.05) .P < 0.05). Those patients staging in N2-3 had a 2.538-fold increase in relative risk of death as compared to those in N0-1. HPV-positive patients have a .719-fold reduction in relative risk of death (0.719 times less) compared with patients that are HPV-negative  might be correlated with human papilloma virus (HPV) infection. However, the relationship between OSCC in a Chinese population and oral HPV infection is unknown. This is of increasing importance because during last decade there have been significant increases of HPV infections in China. It has been proven that HPV infection is correlated to cervical cancer and anal cancer, but this correlation is still unclear in oropharyngeal cancers. Our study has shown that HPV infection in ethnic minorities living in a closed geographical region elevates the risk of tumorigenesis in an area where sexual transmitted diseases are rare.It takes years to develop from HPV to cancer and, as the largest oncogene center in Xinjiang, we have accumulated these cases for years. These cases include the major ethnic groups in a relatively restricted geographical area and consists of people who share the same cultural and food preferences. This study provides clinical data to compare with other high HPV prevalence areas and other ethnic groups.The staging and classification of cancer is an important indicator of clinical treatment and prognosis. In recent years, many studies have shown that HPV is an important and significant factor in the current and future prognosis of patients with head and neck squamous cell carcinoma.P < 0.05). This indicates that HPV-positive patients are more sensitive to radiation and chemotherapy. Ang et al. [P = 0.030).Our results show that HPV-positive patients who are receiving radiation therapy, or chemotherapy, had better 5-year survival rates than HPV-negative patients . This indicates that the HPV-positive status indicates a better future prognosis than for HPV-negative patients. Lassen et al. [Our study including a total of 63 cases of tongue squamous cell carcinoma showed that the overall 5-year survival rate in HPV-positive patients was 47.8%, which is significantly higher than HPV-negative patients (30.3%),  has no impact on prognosis. However, due to the small sample size, this cohort should be expanded and should continue to be followed up.To the best of our knowledge, this study includes the biggest sample of tongue squamous cell carcinoma patients from different ethnic groups in Xinjiang, China. The overall infection rate of HPV was 28.6% (18/63) in this cohort; the 5-year survival rate among the HPV-positive patients was 47.8% and 30.3% for HPV-negative patients. The 3-year and 5-year survival rate for HPV-positive patients who received radiotherapy and chemotherapy are better than those who did not receive radiotherapy and chemotherapy. Multivariate analysis showed that N staging and HPV infection are two independent and significant prognostic factors. HPV-positive patients with tongue squamous cell carcinoma are more sensitive to chemotherapy and higher N staging indicates poorer prognosis.


Carex brevicuspis, one of the dominant species in the Dongting Lake wetland in China. The experiment was conducted with two typical wetland species, C. brevicuspis (target plant) and Polygonum hydropiper (neighbor plant), in a target-neighbor design containing three densities  and two burial depths (0 and 12 cm). The biomass accumulation of C. brevicuspis decreased with increment of P. hydropiper density in the 0 cm burial treatment. However, in the 12 cm burial treatment, biomass accumulation of C. brevicuspis did not change under medium and high P. hydropiper densities. The relative neighbor effect index (RNE) increased with enhancement of P. hydropiper density but decreased with increasing burial depth. The shoot mass fraction decreased with P. hydropiper density in the 12 cm burial treatments, but the root mass fraction was only affected by burial depth. However, the rhizome mass fraction increased with both P. hydropiper density and burial depth. The number of ramets decreased with increasing P. hydropiper density. With increasing burial depth and density, the proportion of spreading ramets increased from 34.23% to 80.44%, whereas that of clumping ramets decreased from 65.77% to 19.56%. Moreover, increased P. hydropiper density and burial depth led to greater spacer length. These data indicate that the competitive effect of P. hydropiper on C. brevicuspis was reduced by sand burial, which was reflected by different patterns of biomass accumulation and RNE at the two burial depth treatments. A change from a phalanx to a guerrilla growth form and spacer elongation induced by sand burial helped C. brevicuspis to acclimate to competition.Both competition and burial are important factors that influence plant growth and structuring plant communities. Competition intensity may decline with increased burial stress. However, experimental evidence is scarce. The aim of this study was to elucidate the role of burial stress in influencing plant competition by investigating biomass accumulation, biomass allocation, and clonal growth performance of  Interactions among species, including competitive, neutral, and positive relationships, play a major role in structuring plant communities , 2. AfteSedimentation alters physical factors such as moisture, temperature, aeration, and other factors of the soil–plant microenvironment factors –16. PlanCompared to non-clonal plants, clonal plants, the dominant wetland plant form, usually have more effective ways to acclimate to burial stress due to their different architectures such as branching angle, spacer length, and growth form , 17. ForCarex brevicuspis, a typical wetland plant of Dongting Lake, were grown at two burial depths and three neighbor plant densities using a target-neighbor design. Here, Polygonum hydropiper, another dominant wetland clonal plant in Dongting Lake, was selected as a neighbor plant. Biomass accumulation, the relative neighbor effect index (RNE), biomass allocation, spacer length, number of ramets, and the proportions of clumping ramets and spreading ramets to total C. brevicuspis ramets were investigated to test the following hypotheses: (1) growth of C. brevicuspis will be inhibited by both higher burial depth and P. hydropiper density; (2) the influence of competition on plant growth will be reduced by burial according to the SGH; (3) the proportion of spreading ramets, spacer length, and rhizome mass fraction will increase with increasing burial depth and P. hydropiper density, and these will further increase under the combination of competition and burial stress.The aim of this study was to test whether burial could reduce the strength of plant competition, and, if that is the case, whether this influence could be explained by the changes in clonal growth performance. In this study, young ramets of The collection of plant materials was approved by the East Dongting Lake National Nature Reserve. The two species used in the experiment are not endangered or protected species.Miscanthus sacchariflorus, middle-elevation species include C. brevicuspis and P. hydropiper, and low-elevation species include Phalaris arundinacea). Sedimentation at a rate of approximately 3–7 cm year−1 has been confirmed as an important driving force regulating community succession in this lake [Dongting Lake  is the second largest freshwater lake and the most typical river-connected lake in China. The wetlands in this lake are characterized by large seasonal water level fluctuations, being completely flooded during May–October and dry during November–April. In this lake, wetland plants are usually distributed along a water-level gradient  and spreading ramets from buds of long rhizomes . Moreover, compared to sexual reproduction, asexual reproduction plays a more important role in vegetation recruitment [P. hydropiper (Polygonaceae) is as an annual herb distributed widely around the world [P. hydropiper can overwinter through belowground rhizomes although the aboveground parts die [P. hydropiper community, the most common concomitant species is C. brevicuspis and other species are less. These two species flower and fruit from April to May in Dongting Lake before flooding begins [C. brevicuspis and P. hydropiper was 0.4–3.1 cm in natural habitats based our field observations in 2009.d Taiwan . The psehe world . In Dongarts die . In the g begins , 25. TheC. brevicuspis and P. hydropiper) were collected in March, 2014 from Junshan County , East Dongting Lake. The vegetation was cut into small blocks (20 cm × 20 cm) for easy transport, and was then transported to an experimental field at the Dongting Lake Station for Wetland Ecosystem Research of the Chinese Academy of Sciences. The vegetation blocks were placed into plastic buckets, which contained 15 cm of soil , to re-sprout new ramets. The plants were watered when necessary.Plants  in a factorial design with eight replicates, based on our field investigation (P. hydropiper densities ranged from 25 to 390 plants m-2). Therefore, the experiment included six treatments: two single-individual treatments  and four mixed-species treatments  of similar size  were cut from plant cultures on March 20, 2014. They were planted into 48 pots (30 cm in height and 16 cm in diameter) filled with 15 cm of the same soil used for plant incubation.The experiment combined two burial depths (0 and 12 cm) and three -1 organic matter, 0.25 g kg-1 exchangeable N, and 0.06 g kg-1 exchangeable P. Tap water  was supplied when necessary. Holes were drilled in the bins at 15 cm depth to keep the water level at 0 cm and we also replenished the water once a week to prevent algal growth.Six pots (one per treatment) were placed into each of eight bigger plastic bins (98 cm × 76 cm × 68 cm), which were placed in an outdoor area with natural sunshine. A one-time burial treatment was initiated seven days after planting. The sand used for burial was collected from a local river (Xiang River) and contained 0.76 g kgThe plants were harvested five months after the experimental treatments. First, plant roots were carefully dug out by hand to keep the connection between ramets. Then, the plants were cleaned with tap water and the clumping ramets and spreading ramets were counted. Clumping ramets were defined as ramets produced from shortened rhizomes (spacer length < 1 cm), while spreading ramets were those produced from the distal part of long rhizomes (spacer length > 1 cm) . The totN) and absence (-N) of neighbors, and X is the larger value of PN- or PN+. Biomass was In (x+1) transformed prior to statistical analysis to conform to the assumptions of normality and homogeneity of variance [The intensity of interspecific competition was quantified using the relative neighbor effect index (RNE) :RNE=(P−variance . RNE is variance . The RNEP. hydropiper density as main factors, were performed to determine the main effects and interactions on biomass accumulation, RNE, biomass allocation, number of ramets, spacer length, and the proportion of spreading ramets and clumping ramets. Multiple comparisons of means were performed using Duncan’s test at the 0.05 significance level. Data were log10-transformed if necessary to reduce the heterogeneity of variances. Normality and homogeneity were tested using a Lilliefors test and Levene’s test, respectively. All analyses were performed using the software SPSS 15.0 for Windows.Two-way ANOVAs, with burial and P. hydropiper density had a significant effect on C. brevicuspis biomass accumulation (P. hydropiper density in the 0 cm burial treatments. However, in the 12 cm burial treatment, biomass accumulation exhibited similar patterns in the medium and high density treatments.mulation ; Fig 2, mulation ; Fig 2. P. hydropiper density (The RNE decreased significantly with increased burial depth and increased significantly with the enhancement of  density ; Fig 2. P. hydropiper density (P. hydropiper density in the 12 cm burial treatments (P. hydropiper density (The shoot mass fraction was significantly influenced by  density ; Fig 3, eatments ; Fig 3. eatments . The rhi density ; Fig 3 a density ; Fig 3, P. hydropiper density (P. hydropiper density (The number of ramets decreased with increasing  density ; Fig 4,  density ; Fig 4.  density ; Fig 4 a density ; Fig 4. P. hydropiper density (The proportions of different ramet types were significantly influenced by both burial depth ; Fig 5 a density ; Fig 5. C. brevicuspis had insignificant changes between the two burial depths. These results are partly inconsistent with our hypothesis 1. Plants that grow in habitats with regular sand burial can usually tolerate a certain degree of burial, and some species even require regular burial to maintain high vigor [C. brevicuspis [P. hydropiper density treatments suggested that a higher density of P. hydropiper intensified competition for resources and available growth space, then limited the growth of C. brevicuspis. This result was supported by the changing pattern of biomass accumulation in P. hydropiper, which was 1.31–1.38 times higher in the high density treatments than that in the medium density treatmtents. Moreover, the relationship between competition and neighbor plant density has been widely documented [The biomass accumulation and number of ramets of gh vigor . Anothervicuspis . The deccumented , 28.C. brevicuspis at the two burial depths indicated that the competition intensity of P. hydropiper to was reduced by burial, which was consistent with the SGH and hypothesis 2. A study conducted in Rookery Bay, Florida found that burial can cause net plant interactions to become more facilitative [P. hydropiper densities could alleviate soil anoxia by releasing oxygen into the soil through well-developed aerenchyma, which is supported by our other studies [Carex rostrata was 2.1 times higher than that without vegetation treatment [The different biomass accumulation and RNE patterns of litative , which m studies , 18. Mor studies , 30. ForC. brevicuspis increased significantly with burial depth and P. hydropiper density. These results are in agreement with hypothesis 3, and the results suggest that a trade-off existed between phalanx and guerrilla growth forms in C. brevicuspis in response to both burial and competition stress. Moreover, our results also indicate that spacer length was significantly affected by interactions between burial and plant density. The spacer length was significantly higher under 12 cm burial treatment than in the 0 cm burial treatment for the high P. hydropiper density treatment only, which indicated that the influence of burial changed significantly among different competitive intensities. This is particularly important considering that spacer elongation costs plants more energy. Regarding treatments with no P. hydropiper and medium P. hydropiper densities, the resource availability might be sufficient for plant growth owing to lower competition intensity. While in the high density P. hydropiper treatments, limited resource availability caused by high competition intensity might promote the placement of more ramets into favorable habitats through spacer elongation.In our experiment, spacer length and the proportion of spreading ramets of Prunella vulgaris L. and Glechoma hederacea L. can increase stolon length in response to competition [Hieracium pilosella L. and Elymus lanceolatus ssp. lanceolatus cannot [A change from the phalanx to guerrilla growth form has been widely confirmed as an effective way for plants to acclimate to various abiotic stresses, including burial , low nutpetition –34, whils cannot , 35. Thes cannot . Anothers cannot .Zostera noltii can transform the nutrients from other organs to rhizomes to meet the energetic requirements of rhizome growth [C. brevicuspis primarily adopts a phalanx growth strategy to monopolize locally abundant resources [C. brevicuspis can allocate more energy to produce a higher proportion of long rhizomes. This clonal growth change is an effective method for the avoidance of burial and competition stress for C. brevicuspis, and it might be an important reason why C. brevicuspis is a dominant species in the Dongting Lake wetland.In this experiment, the rhizome mass fraction increased with increasing burial depth and density, which corresponded with increased spacer length and the proportion of spreading ramets. These results support hypothesis 3. The production of long rhizomes involves greater energy costs. For instance, e growth , and sime growth , 37. In esources . However


Objective. We investigate the prevalence of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) tissues compared to oesophageal tissue from healthy controls, in an Australian cohort. Methods. We conducted a hospital-based case-control study of 99 patients with OSCC and 100 healthy controls to examine the presence of HPV DNA. Paraffin tissues were tested using the PapType high-risk HPV detection and genotyping kit and with INNO-LiPA HPV Genotyping Extra. The biopsy samples were tested for HPV using a PCR-ELISA method based on the L1 consensus primer set PGMY09-PGMY11. Results. HPV DNA of the oncogenic genotype 16 was detected in 1/99 case specimens, a rate of 1010 per 100,000 (95% CI: 30–5500). All control specimens were negative for HPV. Significantly higher rates of smoking, other aerodigestive cancers, and mortality were seen among cases than controls. A pooled analysis of this study and the only other Australian case-control study found that 9/321 cases and 0/155 controls were positive for HPV. The pooled odds ratio for HPV being a risk factor for OSCC was 9.35 (95% CI: 0.47–190.33). Conclusion. Our results suggest that in this multifactorial cancer HPV may be an additional risk factor; although a larger, better powered study is needed. Oesophageal cancer (OC) is currently the sixth most common cause of cancer-related death in the world, claiming the lives of 406,000 people in 2008 . It is tThe multifactorial aetiology of OSCC may explain its highly variable geographical distribution with up to a 500-fold difference in incidence between high-risk areas such as the Transkei region of South Africa, the Caspian Littoral of Iran, and Northern China and low-risk regions such as Western Africa , 6. On aThe International Agency on Research on Cancer (IARC) has acknowledged HPV involvement in head and neck, particularly oropharyngeal, tonsillar, and oral SCC, but has not yet made a conclusive statement about a causal relationship between HPV and OSCC . SyrjaneThe inconsistent observations between individual studies may be attributed to many factors including differences in study design, laboratory techniques, sample types, testing methodology, and the dynamic aetiology of OSCC . A totalWe conducted a case-control study to investigate whether HPV is associated with OSCC in Australia. Case specimens were obtained retrospectively from tumor banks at five hospitals nationwide. These included three teaching hospitals in New South Wales, one in Queensland, and a cancer hospital in Victoria. Control subjects were recruited prospectively in 2010, at the endoscopy clinics of two of the hospitals in NSW.Case subjects were defined as patients who had a histopathologically confirmed diagnosis of OSCC. Five tumour banks across the country were approached and any OSCC specimens available were requested and obtained. Case specimens included 23 genomes amplified, 26 fresh frozen, and 50 formalin-fixed and paraffin-embedded samples. Formalin-fixed and paraffin-embedded samples were reviewed by a pathologist to ensure that appropriate sections were obtained for testing. Case specimens used in this study dated from 1989 to 2009.Controls were defined as healthy subjects with no previous history of gastric or oesophageal malignancy and no underlying chronic illness. In addition, those with any history of antecedent or concurrent precursor lesions for adenocarcinoma, such as Barrett's oesophagus, were excluded from recruitment. Patients who were not suitable for oesophageal biopsy, such as those with a predisposition to bleeding, were also excluded. Subjects were randomly sampled from patients undergoing routine endoscopy for investigation of presumed nonmalignant conditions such as gastrooesophageal reflux disease. Areas of oesophagus biopsied were macroscopically normal in appearance. Three biopsies were obtained from the upper, middle and lower thirds of the oesophagus, for each control.Of a total of 126 controls who were approached, two were excluded due to a previous history of Barrett's oesophagus, three were excluded due to concurrent warfarin therapy which contraindicated biopsy during procedure, and twenty-two people declined invitation to take part in the study.A range of commercial and in-house adapted HPV detection methods were utilized to test all case and control specimens. All testing was carried out at the HPV Labnet, the World Health Organization Western Pacific regional HPV reference laboratory at the Royal Women's Hospital, Victoria, Australia.For paraffin-embedded archival samples, two commercially available assays utilizing PCR and targeting 65 and 150 bp region of L1 were used. The smaller amplicons are particularly suited for archival tissue –27. 5–10Fresh biopsy samples were tested using well-established PGMY09/11 primers either in a PCR-ELISA format as described previously , 29 or oNucleic acid extracted from FFPE was tested using the PapType high-risk HPV detection and genotyping kit  and with the INNO-LiPA HPV genotyping extra (INNO-LiPA)  as both methods amplify a relatively small gene region and are preferred for samples that may be degraded or contain low levels of DNA . Both mePapType detects 14 high-risk and 2 low-risk HPV genotypes using fluorescently labelled primers to simultaneously amplify a 150 base-pair (bp) region of the HPV L1 gene and includes a 288 bp region of the human-specific gene, myosin light chain (MLC-1) as an internal control. PCR product is hybridized to HPV type-specific probes bound to labelled silica microspheres. These detection beads are distinguishable by their size and fluorescent intensity using flow cytometry  and the data interpreted using QPlots (Genera Biosystems).10-modified primers), followed by reverse line blot hybridization, detects and genotypes 28 different HPV genotypes, including 18 high-risk HPVs , 6 low-risk HPVs , and 3 other non-classified HPVs , targeting a 65 bp fragment of the HPV L1 ORF. DNA and WGA DNA samples were tested using PapType as described above, because DNA volumes were limited.InnoLipa is a multiplex PCR-based assay (SPFNucleic acid from biopsy samples and whole genome amplified DNA were amplified using HPV L1 consensus primer set PGMY09-PGMY11 . PCR proAny biopsy samples that tested positive for HPV by either PapType or the PGMY09-PGMY11 PCR-ELISA were subsequently tested using the LINEAR ARRAY HPV Genotyping Test (Roche) with the modification of using an automated blot processor, BeeBlot , for the hybridization and washing steps, as previously validated by the Royale Women's Hospital laboratory –32.β-globin and low β-globin controls must have been visible for the strip results to be considered valid for that sample.In addition to being tested by Linear Array using 50 µL of DNA as per manufacturer's instructions, these samples were also tested using 10 µL DNA (plus 40 µL water) to minimize the potential effect on PCR competition by an overabundance of human genomic DNA in the sample. Both high Based on available literature, we estimated the presence of HPV DNA to be at least 15% in cases and less than 3% in controls. To detect this difference with 95% confidence and 80% power, 55 subjects per arm are required. We therefore aimed to recruit 100 cases and 100 controls. Due to the small number of annual OSCC cases across Australia, all cancer samples included in this study were archival specimens from tumor banks.Data collection for cases included retrieval of information primarily from hospital medical records and, where possible, direct patient contact via telephone interviews. One investigator (SL) reviewed medical records and collated the various sources of data for OSCC cases. Detailed data collection for case subjects was not possible for several reasons. Many of the OSCC patients, whose tissues were used in our study as cases, were deceased at the time this study was conducted and therefore information could only be obtained from hospital medical records and patient files from the consulting rooms. In addition, some hospitals had destroyed medical records of patients whose admissions had occurred more than 10 years ago. Several patients had been treated at multiple medical facilities across the state and the country and internationally, at various stages of their illness, thereby making it difficult to obtain a complete record. Finally, some OSCC patients either were not contactable or declined invitations to participate in a phone interview. In contrast, all relevant information was collected prospectively for each of the 100 control subjects during their visit to endoscopy clinics. Control data were collected prospectively prior to oesophageal biopsy by an investigator-administered survey by two investigators, SL and AM.P values were calculated using the Epi Info 3.5.5 software program [As the data collection for cases was retrospective (and many cases were deceased) and that for controls was prospective, there was a substantial difference in the quality and quantity of information obtained between cases and controls. As a result of the inconsistency and incompleteness of data in cases compared to control subjects in the study, data analysis for other risk factors  for OSCC was not possible. Therefore, this is mainly a descriptive study concentrating primarily on prevalence of HPV DNA in OSCC compared to normal oesophageal tissue.  program .OSCC is a rare cancer in Australia, and collection of control specimens entails an invasive oesophageal procedure on healthy subjects. As such, large studies are unfeasible. In order to improve the statistical power, a pooled analysis was conducted combining the results of the only other Australian case-control studies , which fEthics approval for this study was obtained from the lead ethics committee at Northern Sydney Central Coast Health in Sydney, Australia. In addition, ethics approval was obtained from each of the five sites of specimen collection. All participants in the study were provided with printed information regarding the study and written consent was obtained prior to recruitment. Reading material provided to recruits pertaining to the study and all patient data collection forms were approved by the Lead Ethics Committee.P < 0.01). Case (OSCC) subjects also had a higher rate (17%) of past aerodigestive cancers, including hypopharyngeal and tonsillar SCCs, while none of the control subjects had a past history of malignancy (P < 0.001) as per our selection criteria. Thirty-nine of the ninety-nine case subjects were deceased at the time this study was conducted. Overall, higher rates of smoking, aerodigestive cancers, and mortality were seen among cases than controls. However, alcohol consumption rates were higher in the control group than in the cases.Two-thirds (65%) of case subjects smoked during their lifetime compared to 45% of controls . The HPV genotype detected in the case subject was the oncogenic type HPV16. The patient with the HPV positive OSCC sample was a Caucasian female, aged 62 years at the time of diagnosis of her OSCC. She had an invasive, moderately differentiated SCC of the esophagus and died within six weeks of diagnosis. She had a 45 pack-year history of smoking and was a smoker at the time of her diagnosis. She also had a history of heavy alcohol use.The pooled analysis with the only other Australian case-control study  showed tMost developed countries are known as low-risk for OSCC due to stable or declining OSCC incidence rates over the last few years. In Australia, the major risk factors for OSCC appear to be smoking and alcohol. Our results suggest that, in this multifactorial cancer, oncogenic HPV may well be a risk factor, but the study was underpowered. The confidence limits around the rate of HPV detection in OSCC in our study ranged from 30 to 5500 per 100,000 cancers, and the rate is consistent with that found in the previous Australian case-control study . The finFrom 1986 to present, there have been only three studies conducted in Australia, to determine whether HPV is a causative factor in OSCC. A variety of methods have been used for HPV detection in OSCC specimens, producing mixed results. The first study carried out in 1986 employed filter in situ hybridization (FISH) methodology and detected HPV in 5/10 (50%) of OSCC specimens and no HPV in macroscopically normal oesophageal tissue biopsied adjacent to the OSCC tumor . SubsequThe pooled analysis of this study with ours and the odds ratio of 9.35 are suggestive of HPV as a risk factor for OSCC but did not reach statistical significance. Clearly, OSCC is a multifactorial cancer, and other risk factors such as alcohol and smoking predominate in countries like Australia. However, the consistency of findings between these two studies and the pooled analysis point, as well as our meta-analysis , point tOur study adds to the small body of work which currently exists on this topic in the Australian population. In terms of prevalence of HPV in OSCC, there have been some low-risk settings such as USA, Germany, Portuga, and Italy, where high HPV detection rates have been reported in OSCC samples –39.A limitation of this study is the small sample size, and the fact that only one sample was positive for HPV. Studies of OSCC and HPV are difficult and invasive, making large sample size unfeasible. Collection of control specimens entails an oesophageal biopsy, which is an invasive procedure conducted in a healthy subject, and makes it difficult to increase the number of controls to improve statistical power. In fact, our study had almost double the number of controls of the other Australian study . The larIn summary, our study adds to the very few studies done in Australia, a low-risk country for OSCC. The findings, whilst not conclusive, are consistent with the findings of our meta-analysis and indicate that there may be a role of HPV in OSCC . The rec


Peer influence and social networking can change female adolescent and young adult behavior. Peer influence on preferences for male human papillomavirus (HPV) vaccination has not been documented. The primary aim of this study was to determine if women had preferences about male sexual partner HPV vaccination receipt.A prospective survey of women 18–26 years of age was conducted at an urban university student health clinic. Education about the two HPV vaccines, cervical cancer and genital warts was provided. Women self-reported their demographic and medical history data, as well as their own preferences for HPV vaccine and their preferences for their male partner HPV vaccine using a 5 point Likert scale. 601 women, mean age of 21.5 years (SD 2.4), participated between 2011 and 2012. Nearly 95% of respondents were heterosexual; condoms and contraceptives were used in over half of the population. Regardless of the woman's vaccination status, women had significantly higher (strongly agree/agree) preferences for the male partner being vaccinated with HPV4 than not caring if he was vaccinated . This preference was repeated for sexual risk factors and past reproductive medical history. Women who received HPV4 compared to those choosing HPV2 had a significantly lower proportion of preferences for not caring if the male partner was vaccinated .Women preferred a HPV vaccinated male partner. Peer messaging might change the male HPV vaccination uptake. Preferences for prophylactic HPV vaccines have been studied from the perspective of parents The primary aim of this study was to determine the preference rankings women have about HPV vaccination for a male sexual partner and how these vary by her reproductive health experiences.This prospective study was approved by the University of Missouri Kansas City (UMKC) Social Sciences Adult Institutional Review Board (SSIRB) (#SS10-56X) as an exempt study not requiring verbal or written consent and is part of a 601 person study on how women decide to accept or reject the HPV vaccination All women under 27 years old presenting for care at the UMKC Student Health and Wellness office between January 2011 and August 2012 were invited at the time of check-in to participate in this cervical cancer prevention educational intervention. This time frame allowed for 5 academic terms to be surveyed providing the opportunity to reach as many female students as possible, including those who may have taken time away.Cervical cancer prevention information was written at the seventh grade reading level, as required by the SSIRB. It addressed the three methods of prevention in this age group: Pap testing, each of the two prophylactic HPV vaccines and the combination of Pap testing and HPV vaccination. The strengths and limitations of the three methods were outlined including colposcopy and treatment of detected abnormalities, the HPV genotypes directly covered by each vaccine as well as those prevented by cross-protection, the efficacy of less than three doses, and current evidence for duration of vaccine efficacy. Genital wart coverage was included. Subjects self-reported demographic and past medical history information.The HPV vaccine preference survey used a 5 point Likert scale (1 = strongly disagree to 5 = strongly agree) to elicit women's preferences for her male sexual partner. Partner preference choices were presented as “I want my sexual partner to be vaccinated with Gardasil to prevent spreading warts to me” vs. “I don't care if my sexual partner is vaccinated”. If she did not have a male partner, her survey was censored. We did not query preferences for concurrent male partners. No identifying information was collected.Frequencies, Chi-square and Fisher's exact test were used to show nonrandom associations between two categorical variables with a p<0.05 considered significant. Mann Whitney U testing was used to compare median preference rankings; Students' t-test was used for simplifying reporting. Statistica version 12 was used for the analysis Over the five academic terms from January, 2011 through August 2012, 601 women under the age of 27 years agreed to participate in the cervical cancer prevention educational intervention. The average age of the participating woman was 21.5 years (SD 2.4), of whom 62% were white, 18% black, 4% Hispanic, 9% Asian and 7% of other races/ethnicities . Over 90Overall, women had significantly higher preferences for a male partner who was vaccinated than not (median 4 (95% CI: 3–5) vs. 2 (1–3); mean rank 3.9 (SD 1.1) vs. 2.4 (1.1), p<0.001). The preference for male vaccination had significantly higher preference rankings than not caring if the male is vaccinated by women who are condom and oral contraceptive users, as well as women with a history of an abnormal Pap test, HPV infection, colposcopy, or other STI's . Few stuThis work shows that women prefer their male partners to be vaccinated regardless of their choice of vaccine for themselves. This preference is pronounced when the woman has one or more perceived vulnerabilities, e.g. high number of lifetime sexual partners, a past history of HPV infection, abnormal Pap testing, colposcopy or another STI. No other study has reported on women's preferences for male HPV vaccination. One study has reported male preferences for cervical cancer screening every 3 years among female family members without any additional preference for HPV vaccination The cost-effectiveness models show that male HPV vaccination is only cost effective when several conditions are met. These include receiving all three doses on time, assuming lifetime duration of efficacy, vaccination occurs prior to HPV infection and vaccination coverage in the population of potential partnering females is less than 50% Other male HPV vaccination studies have focused on parental views about vaccinating sons, male attitudes about vaccine receipt, with some focus on men as male partners, and the provider recommendation for male HPV vaccination This study was conducted on an urban US Midwest college campus among women 18–26 years of age, and as such may not be representative of the perspectives of young adolescent girls or their parents. We did not require the women who had been vaccinated to specify how many doses of vaccine they received.We did not offer women the choice of no vaccination for herself and vaccination for her male partner; hence we do not know what proportion of women would choose to shift the burden of HPV infection prevention to the male partner. Likewise, we did not ask women their last menstrual period date or cycle regularity, as some sexual preferences for male behavior are linked to the reproductive cycle Women rank highly their preferences for male HPV vaccination. These choices are intensified if the woman has received at least one dose of HPV4 herself.


OGG1)  are registered at the National Center for Biotechnology Information (NCBI). OGG1-1a is present in the nucleus, whereas the other seven isoforms are present in the mitochondria. Recombinant OGG1-1a has been purified and enzyme kinetics determined. OGG1(s) in mitochondria have not been fully characterized biochemically until recently. The major mitochondrial OGG1 isoform, OGG1-2a , has also been expressed and purified; however, its activity is unresolved. Recently, we purified recombinant mitochondrial OGG1-1b and found that it was an active OGG1 enzyme. We reported its enzyme kinetics and compared the results with those of OGG1-1a. The reaction rate constant of OGG1-1b 8-oxoG glycosylase activity (kg) was 8-oxoG:C > > 8-oxoG:T > > 8-oxoG:G > 8-oxoG:A and was similar to that of OGG1-1a under single-turnover conditions ([E] > [S]). Both OGG1-1b and OGG1-1a showed high specificity towards 8-oxoG:C. The reaction rate constant of OGG1-1b N-glycosylase/DNA lyase activity (kgl) was 8-oxoG:C > 8-oxoG:T ≃ 8-oxoG:G > > 8-oxoG:A and that of OGG1-1a was 8-oxoG:C > 8-oxoG:T, 8-oxoG:G and 8-oxoG:A. The kgl of OGG1-1b and OGG1-1a is one order of magnitude lower than the corresponding kg value. OGG1-1b showed an especially low kgl towards 8-oxoG:A. Comparable expression of OGG1-1a and OGG1-1b was detected by RT-PCR in normal human lung tissue and lung cell lines. These results suggest that OGG1-1b is associated with 8-oxoG cleavage in human lung mitochondria and that the mechanism of this repair is similar to that of nuclear OGG1-1a. Currently, the other five mitochondrial OGG1 isoforms have not been isolated. I summarize information on OGG1 isoform mRNAs, coding DNA sequences and amino acid sequences that are archived by the National Center for Biotechnology Information.Eight alternatively spliced isoforms of human 8-oxoguanine DNA glycosylase ( Similar substrate specificity of OGG1-1b and OGG1-1a against 8-oxoG:C and 8-oxoG:A was observed. Product formation was higher against 8-oxoG:C than 8-oxoG:A for OGG1-1b and OGG1-1a. APEX nuclease 1  was required to promote DNA strand breakage by OGG1-1b. These results suggest that OGG1-1b is associated with 8-oxoG cleavage in human lung mitochondria and that the mechanism of this repair is similar to that of nuclear OGG1-1a.The reaction rate constants for 8-oxoG glycosylase activity  was cloned as an alternatively spliced isoform of OGG1 in 1997 by Abratani et al. [OGG1-2a was demonstrated by northern blot analysis and by RT-PCR in various tissues [Human i et al.  and Roldi et al.  and HeLai et al. . In addi tissues .in vitro. They examined OGG1 activity with 100 nM OGG1-2a and 10 nM oligonucleotide as the substrate, and found no activity. In the control experiment, they examined 1 nM OGG1-1a and 10 nM oligonucleotide substrate and found active OGG1 activity. Roldán-Arjona et al. [Inconsistent findings regarding OGG1-2a protein have been published. Hashiguchi et al.  purifieda et al.  reportedRecently, Su et al. suggested that OGG1-2a (written as β-OGG1) was an accessory factor in mitochondrial Complex I function and was related to mitochondrial base excision repair .OGG1-1c was cloned as an alternative splicing isoform of OGG1 in 1997 by Abratani et al. [OGG1-1c was demonstrated by RT-PCR in some human tissues including the colon [OGG1-2b, −2c, −2d, and −2e was demonstrated by RT-PCR in a small number of human tissues including the cerebrum and kidney, and in the Jurkat cell line by Nishioka et al. [i et al. . Expresshe colon . Localizhe colon . The expa et al. . These pOGG1, as derived from the gene and nucleotide database of the NCBI (http://www.ncbi.nlm.nih.gov/gene/4968). Table OGG1 CDS, nt length, identity to OGG1-1a CDS and identity to OGG1-2a CDS according to the NCBI and examined by BLAST (http://blast.ncbi.nlm.nih.gov/Blast.cgi). Table Table OGG1-1a mRNA has exons 1–7 and no exon 8. The CDS begins at nt 344 in exon 1, and the nt sequence of 1292–1381 (90 bp) in exon7 is the last part of the CDS. The OGG1-1a CDS is composed of part of exon 1, all of exons 2, 3, 4, 5, 6 and part of exon 7.The OGG1-1b mRNA. The nt sequence 1242–1318 (77 bp) in exon 6 is the last part of the CDS. Although the nt sequence of 1536–1882 (347 bp) in exon 6 of the OGG1-1b mRNA is the same as the entire exon 7 of the OGG1-1a mRNA , the former represents part of the 3′-UTR. As for the OGG1-1b CDS, the nt sequence of 1242–1291 from exon 6 of the OGG1-1b mRNA is identical to the whole exon 6 CDS of the OGG1-1a mRNA. The OGG1-1b mRNA nt sequence of 1292–1294 is identical to the first part of the exon 7 CDS of the OGG1-1a mRNA. The OGG1-1b mRNA 1295–1318 sequence (24 bp), which encodes seven amino acids and the stop codon, differs from the 1295–1318 sequence (CDS) from exon 7 of the OGG1-1a mRNA, resulting in a different amino acid sequence for the last seven amino acids of OGG1-1b when compared with the OGG1-1a sequence.Exon 6 is the last exon of OGG1-1c mRNA has exon 7, but the nt sequence of this exon is different from that of OGG1-1a mRNA. It also has no exon 8. The nt sequence 1292–1576 (285 bp) from exon 7 of the OGG1-1c mRNA is the last part of the CDS, but differs from the 1292–1381 CDS (90 bp) from exon 7 of the OGG1-1a mRNA. The nt sequence of 1309–1398 (90 bp) of the OGG1-1c mRNA, a part of the CDS from exon 7, is identical to 1292–1381 (90 bp) of the OGG1-1a mRNA, the entire exon 7 nt sequence.The OGG1 mRNAs have exon 8. All type 2 OGG1 mRNAs have the same exon 8 nt sequence (861 bp). The OGG1-2a mRNA has no exon 7. The nt sequence 1292–1618 (327 bp) in exon 8 of the OGG1-2a mRNA is the last part of the CDS and the sequence 1619–2158 (540 bp) is the 3′ UTR.Only type 2 OGG1-2b mRNA has no exons 5–7. The nt sequence 1091–1417 (327 bp) in exon 8 of the OGG1-2b mRNA is the last part of the CDS and is identical to the OGG1-2a CDS, resulting in an identical amino acid sequence for the last 108 amino acids of OGG1-2a and OGG1-2b.The OGG1-2c mRNA has no exons 4–7. The nucleotide sequence 909–931  from exon 8 of the OGG1-2c mRNA is the last part of the CDS, resulting in a different amino acid sequence from that of OGG1-2a and OGG1-2b. The nt sequence 932–1775 (844 bp) is the 3′-UTR and has a different length to the 3′-UTRs from the OGG1-2a (540 bp) and OGG1-2b mRNAs (540 bp).The OGG1-2d mRNA has exons 7–8. The whole nt sequence of exon 7, 1292–1391 (100 bp), in the OGG1-2d mRNA is a CDS. The nucleotide sequence of 1392–1414  from exon 8 of the OGG1-2d mRNA is the last part of the CDS, and gives rise to the same six amino acid sequence as that of the OGG1-2c protein. The nt sequence of 1415–2258 (844 bp) is the 3′-UTR.The OGG1-2e mRNA has exons 7 and 8. The nucleotide sequence 1292–1312 (21 bp for six amino acids and the stop codon) from the first part of exon 7 of the OGG1-2e mRNA is the last part of the OGG1-2e CDS, resulting in an amino acid sequence that differs from the exon 7 CDS of OGG1-1a, OGG1-1c, and OGG1-2d. The nt sequence 1313–1344 is a part of the 3′-UTR. Exon 8 (861 bp) of the OGG1-2e mRNA is a continuous 3′-UTR. The whole exon 7 nt sequence 1292–1344 (53 bp) of the OGG1-2e mRNA is identical to part of the nt sequence 1339–1391 (53 bp) in exon 7 of the OGG1-2d mRNA.The OGG1) are registered with the NCBI. OGG1-1a is present in the nucleus, whereas the other seven isoforms are present in mitochondria. Recombinant OGG1-1a has been purified and its enzyme kinetics studied. The mitochondrial major OGG1 isoform, OGG1-2a , has been purified; however, the OGG1 activity of this enzyme was unusual and has not been determined. Recently, we purified recombinant mitochondrial OGG1-1b and showed that it is an active OGG1 enzyme. We reported its enzyme kinetics and compared the results with the corresponding kinetics of OGG1-1a. The OGG1 activity of OGG1-1b was similar to that of OGG1-1a, except for the kgl against 8-oxoG:A. The OGG1-1b mRNA was detected by RT-PCR in normal human lung tissue and lung cells lines. These results suggest that OGG1-1b is associated with 8-oxoG cleavage at least in human lung mitochondria, and the repair mechanism is similar to that of nuclear OGG1-1a. Currently, the other five mitochondrial OGG1 isoforms have not been purified.Eight alternatively spliced isoforms of human 8-oxoguanine DNA glycosylase (