Seropositivity to non-vaccine incorporated genotypes induced by the bivalent and quadrivalent HPV vaccines: A systematic review and meta-analysis.

BACKGROUND: Human papillomavirus vaccines have demonstrated remarkable efficacy against persistent infection and disease associated with vaccine-incorporated genotypes and a degree of efficacy against some genetically related, non-vaccine-incorporated genotypes. The vaccines differ in the extent of cross-protection against these non-vaccine genotypes. Data supporting the role for neutralizing antibodies as a correlate or surrogate of cross-protection are lacking, as is a robust assessment of the seroconversion rates against these non-vaccine genotypes. METHODS: We performed a systematic review and meta-analysis of available data on vaccine-induced neutralizing antibody seropositivity to non-vaccine incorporated HPV genotypes. RESULTS: Of 304 articles screened, 9 were included in the analysis representing ca. 700 individuals. The pooled estimate for seropositivity against HPV31 for the bivalent vaccine (86%; 95%CI 78-91%) was higher than that for the quadrivalent vaccine (61%; 39-79%; p=0.011). The pooled estimate for seropositivity against HPV45 for the bivalent vaccine (50%; 37-64%) was also higher than that for the quadrivalent vaccine (16%; 6-36%; p=0.007). Seropositivity against HPV33, HPV52 and HPV58 were similar between the vaccines. Mean seropositivity rates across non-vaccine genotypes were positively associated with the corresponding vaccine efficacy data reported from vaccine trials. CONCLUSIONS: These data improve our understanding of vaccine-induced functional antibody specificity against non-vaccine incorporated genotypes and may help to parameterize vaccine-impact models and improve patient management in a post-vaccine setting

Oral Human Papillomavirus Infection in Men Who Have Sex with Men: A Systematic Review and Meta-Analysis.

BACKGROUND: The epidemiology of oral human papillomavirus (HPV) infection in men who have sex with men (MSM) differs from anogenital HPV infection. The impact of HPV vaccination has, to date, largely focussed on anogenital outcomes. Vaccination of MSM in the UK has been recommended and, if implemented, baseline estimates of oral HPV prevalence will be useful. METHODS: We searched Medline, Embase and psycINFO databases for studies reporting prevalence, incidence, and clearance of oral HPV infection in MSM. We performed a random-effects meta-analysis and meta-regression on prevalence estimates and summarised within-study risk factors for oral HPV DNA detection and incidence/clearance rates. We also performed a meta-analysis of the effect of MSM on oral HPV prevalence compared to heterosexual men. RESULTS: 26 publications were identified. The pooled prevalence of oral HPV16 from twelve estimates was 3.0% (95%CI 0.5-5.5) in HIV-negative and 4.7% (95%CI 2.1-7.3) in HIV-positive MSM. Median age of study participants explained 38% of heterogeneity (p<0.01) in HPV prevalence estimates (pooled = 17% and 29% in HIV-negative and HIV-positive, respectively; 22 estimates). Nine studies compared MSM to heterosexual men and found no difference in oral HPV prevalence (pooled OR 1.07 (95%CI 0.65-1.74)). The clearance rate was higher than incidence within studies. Type-specific concordance between oral and anogenital sites was rare. CONCLUSION: There was substantial heterogeneity between estimates of oral HPV prevalence in MSM populations that was partly explained by HIV status and median age

Frequency and risk factors for prevalent, incident, and persistent genital carcinogenic human papillomavirus infection in sexually active women: community based cohort study

Objective To investigate frequency and risk factors for prevalent, incident, and persistent carcinogenic human papillomavirus (HPV) in young women before the introduction of immunisation against HPV types 16 and 18 for schoolgirls

Male Circumcision and STI Acquisition in Britain: Evidence from a National Probability Sample Survey.

BACKGROUND: It is well-established that male circumcision reduces acquisition of HIV, herpes simplex virus 2, chancroid, and syphilis. However, the effect on the acquisition of non-ulcerative sexually transmitted infections (STIs) remains unclear. We examined the relationship between circumcision and biological measures of three STIs: human papillomavirus (HPV), Chlamydia trachomatis and Mycoplasma genitalium. METHODS: A probability sample survey of 15,162 men and women aged 16-74 years (including 4,060 men aged 16-44 years) was carried out in Britain between 2010 and 2012. Participants completed a computer-assisted personal interview, including a computer-assisted self-interview, which asked about experience of STI diagnoses, and circumcision. Additionally, 1,850 urine samples from sexually-experienced men aged 16-44 years were collected and tested for STIs. Multivariable logistic regression was used to calculate adjusted odds ratios (AOR) to quantify associations between circumcision and i) self-reporting any STI diagnosis and ii) presence of STIs in urine, in men aged 16-44 years, adjusting for key socio-demographic and sexual behavioural factors. RESULTS: The prevalence of circumcision in sexually-experienced men aged 16-44 years was 17.4% (95%CI 16.0-19.0). There was no association between circumcision and reporting any previous STI diagnoses, and specifically previous chlamydia or genital warts. However, circumcised men were less likely to have any HPV type (AOR 0.26, 95% confidence interval (CI) 0.13-0.50) including high-risk HPV types (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and/or 68) (AOR 0.14, 95% CI 0.05-0.40) detected in urine. CONCLUSIONS: Circumcised men had reduced odds of HPV detection in urine. These findings have implications for improving the precision of models of STI transmission in populations with different circumcision prevalence and in designing interventions to reduce STI acquisition

Human Papillomavirus Antibody Reference Reagents for Use in Postvaccination Surveillance Serology

Suitably controlled serosurveillance surveys are essential for evaluating human papillomavirus (HPV) immunization programs. A panel of plasma samples from 18-year-old females was assembled, the majority of the samples being from recipients of the bivalent HPV vaccine. Antibody specificities were evaluated by three independent laboratories, and 3 pools that displayed no antibodies to any HPV type tested or intermediate or high levels of antibody to HPV16, HPV18, HPV31, and HPV45 were created. These pools will be useful as control reagents for HPV serology

Epidemiology of Mycoplasma genitalium in British men and women aged 16–44 years: evidence from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

BACKGROUND: There are currently no large general population epidemiological studies of Mycoplasma genitalium (MG), which include prevalence, risk factors, symptoms and co-infection in men and women across a broad age range. METHODS: In 2010-–12, we conducted the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability sample survey in Britain. Urine from 4507 sexually-experienced participants, aged 16–44 years, was tested for MG. RESULTS: MG prevalence was 1.2% [95% confidence interval (CI): 0.7–1.8%] in men and 1.3% (0.9–1.9%) in women. There were no positive MG tests in men aged 16–19, and prevalence peaked at 2.1% (1.2–3.7%) in men aged 25–34 years. In women, prevalence was highest in 16–19 year olds, at 2.4% (1.2–4.8%), and decreased with age. Men of Black ethnicity were more likely to test positive for MG [adjusted odds ratio (AOR) 12.1; 95% CI: 3.7–39.4). For both men and women, MG was strongly associated with reporting sexual risk behaviours (increasing number of total and new partners, and unsafe sex, in the past year). Women with MG were more likely to report post-coital bleeding (AOR 5.8; 95%CI 1.4–23.3). However, the majority of men (94.4%), and over half of women (56.2%) with MG did not report any sexually transmitted infection (STI) symptoms. Men with MG were more likely to report previously diagnosed gonorrhoea, syphilis or non-specific urethritis, and women previous trichomoniasis. CONCLUSIONS: This study strengthens evidence that MG is an STI. MG was identified in over 1% of the population, including in men with high-risk behaviours in older age groups that are often not included in STI prevention measures

Epidemiology of genital warts in the British population: implications for HPV vaccination programmes.

OBJECTIVES: To estimate the prevalence of, and describe risk factors for, genital warts (GWs) in the British population, following the introduction of the bivalent (human papillomavirus (HPV)-16/18) vaccination programme in girls, and prior to the switch to quadrivalent (HPV-6/11/16/18) vaccine (offering direct protection against GWs) and compare this with GW diagnoses in the prevaccination era. METHODS: Natsal-3, a probability sample survey in Britain, conducted in 2010-2012, interviewed 9902 men and women aged 16-44. Natsal-2, conducted in 1999-2001, surveyed 11 161 men and women aged 16-44. Both surveys collected data on sexual behaviour and sexually transmitted infection diagnoses using computer-assisted interview methods. RESULTS: In Natsal-3, 3.8% and 4.6% of sexually experienced men and women reported ever having a diagnosis of GWs, with 1.3% of men and 1.7% of woman reporting a GWs diagnosis in the past 5 years. GWs were strongly associated with increasing partner numbers and condomless sex. Diagnoses were more frequent in men who have sex with men (MSM) (11.6% ever, 3.3% past 5 years) and in women reporting sex with women (10.8% ever, 3.6% past 5 years). In the age group who were eligible for vaccination at the time of Natsal-3 (16-20 years), a similar proportion of same-aged women reported a history of GWs in Natsal-2 (1.9%, 1.1-3.4) and Natsal-3 (2.6%, 1.5-4.4). CONCLUSIONS: These data provide essential parameters for mathematical models that inform cost-effectiveness analyses of HPV vaccination programmes. There was no evidence of population protection against GWs conferred by the bivalent vaccine. Even with vaccination of adolescent boys, vaccination should be offered to MSM attending sexual health clinics

Oral human papillomavirus (HPV) infection in men who have sex with men: prevalence and lack of anogenital concordance.

OBJECTIVES: To estimate the prevalence of oral detectable human papillomavirus (HPV) DNA in HIV-negative men who have sex with men (MSM) attending a sexual health clinic in London and concordance with anogenital HPV infection. Such data are important to improve our understanding of the epidemiology of oral HPV and the potential use of vaccines to prevent oropharyngeal cancers. METHODS: Paired oral rinse samples and anogenital samples were available from 151 HIV-negative MSM within a larger cross-sectional survey. All samples were tested in parallel for 21 types of HPV DNA using an in-house assay. RESULTS: The median age of participants was 30 (IQR 25-35). The prevalence of any oral HPV and of high-risk HPV (HR-HPV) was 13.7% (n=21; 95% CI 8.7 to 20.2) and 5.9% (n=9; 95% CI 2.7 to 10.9) compared with 64.9% (n=98; 95% CI 56.7 to 72.5) and 34.4% (n=52; 95% CI 26.9 to 42.6) in any anogenital sample, respectively. The prevalence of types prevented by the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccines was 1.3% (95% CI 0.2 to 4.7), 2.6% (95% CI 0.7 to 6.6) and 4.6% (95% CI 1.9 to 9.3), respectively. There was no concordance between HPV genotypes detected in oral and anogenital sites. CONCLUSIONS: HR-HPV DNA, including HPV 16/18, was detected in oral specimens from HIV-negative MSM attending sexual health clinics, suggesting a potential role for vaccination, but is far less common than anogenital infection. How this relates to the risk and natural history of HPV-related head and neck cancers warrants further study. Lack of concordance with anogenital infection also suggests that oral HPV infection should be considered separately when estimating potential vaccine impact

Human papillomavirus (HPV) in young women in Britain: Population-based evidence of the effectiveness of the bivalent immunisation programme and burden of quadrivalent and 9-valent vaccine types.

BACKGROUND: In 2008, the UK introduced an HPV immunisation programme in girls. Population-based prevalence estimates of bivalent (HPV-16/18), quadrivalent (HPV-6/11/16/18) and 9-valent (HPV-6/11/16/18/31/33/45/52/58) vaccine types, and comparison over time, are needed to monitor impact, evaluate effectiveness and guide decision-making on vaccination strategies. METHODS: The third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) in 2010-12, tested urine for HPV from 2569 sexually-experienced women aged 16-44. We report type-specific HPV prevalence and compare results with 1798 women in Natsal-2 (1999-2001) using age-adjusted prevalence ratios (APR). FINDINGS: In Natsal-3, 4.2% of women aged 16-44y were positive for HPV-16/18 and 2.9% for HPV-6/11. In 16-20 year olds, 4.5%, 10.8% and 20.7% had at least one bivalent, quadrivalent or 9-valent vaccine type, respectively. Three-dose vaccine coverage was 52.0% in women aged 18-20y. In this age group, HPV-16/18 prevalence was lower in Natsal-3 than Natsal-2 (5.8% vs 11.2%; APR=0.48[95%CI: 0.24-0.93]), however, prevalences of HPV-6/11, HPV-31/33/45 and HPV-52/58 were unchanged. HPV-16/18 prevalence was also unchanged in women aged 21-44y (APR=0.85[0.61-1.19]). INTERPRETATION: These probability surveys provide evidence of the impact of the bivalent immunisation programme. Reductions were specific to HPV-16/18 and to the age group eligible for vaccination. However, substantial vaccine-preventable HPV remains