Attendance of MSM at Genitourinary Medicine services in England: implications for selective HPV vaccination programme (a short communication)

Background Human papillomaviruses (HPV) immunisation programmes for female adolescents in the UK offer relatively little benefit to men who have sex with men (MSM). Targeted HPV vaccination for MSM may reduce the high incidence of HPV-related disease among MSM. We used national data from sexual health clinics to calculate the number of MSM attending these clinics throughout England from 2009 to 2014 and to identify their characteristics, to inform the implementation of a targeted HPV vaccination programme in MSM. Methods We used the Genitourinary Medicine Clinic Activity Dataset (GUMCADv2) to obtain data for men aged 15–70 years who had attended a GUM clinic in England from 2009 to 2014. We analysed both numbers of MSM attending and number of GUM attendances, age at first attendance, ethnicity and geographical area of the clinic in England. Results A total of 374 983 MSM attended sexual health services in England between 2009 and 2014. Median age of presentation was 32 years (IQR 25–41) and showed regional geographical variation. Of all men attending sexual health clinics in England, the highest proportion of those identifying as MSM was in London (21%). Excluding visits within 1 month of an initial attendance, 49% of all MSM re-attended within 12 months and 58% within 24 months. MSM aged ≥36 years reattended more frequently than younger MSM. 51% reattended at least twice within 24 months of initial visit. Conclusions The majority of MSM reattend clinic at least once within a 24-month period, potentially facilitating the delivery of a three-dose HPV vaccination programme. This would reduce the burden on sexual health clinics and cost to local authorities due to extra visits if HPV vaccination were to be delivered through these services

Assessment of the population-level impact of a high coverage HPV immunisation programme in young females

Human papillomavirus (HPV) infection is common in England. Persistent HPV infection can cause cervical and other HPV-related cancers. In clinical trials, HPV vaccination was found to have very high efficacy against HPV infection and early HPV-related disease. The National HPV Immunisation Programme, using HPV16/18 vaccine, was introduced in the UK in September 2008 for females aged up to 18 years old. This thesis aims to evaluate the equity and coverage of HPV vaccination in England and the population-level impact of the vaccination programme on infection and early disease outcomes in young females. In this thesis, serological surveillance confirmed high coverage of HPV vaccination in the targeted female population. However, surveillance among women at higher risk of HPV infection indicated lower coverage among those born outside of the UK, from more deprived areas or with a previous diagnosis of chlamydia infection. The same higher-risk population was used to investigate a previous ecological observation of reduced genital warts diagnoses since the vaccination was introduced. I designed and conducted a case-control study to estimate the effectiveness of HPV16/18 vaccination against genital warts (which are largely caused by HPV6/11). This study found no evidence that HPV16/18 vaccination offered cross-protection against warts (adjusted odds ratio (95% CI):1.02 (0.72- 1.45)). My analyses of HPV infection surveillance data within the post-vaccination period (2010-2016) demonstrated substantial declines in prevalence of HPV16/18 infection in 16-18 year olds (8.2% in 2010/2011 compared to 1.6% in 2016) and of HPV31/33/45 (6.5% to 0.6%). This work provides evidence of substantial direct protection against HPV16/18 and some type-specific cross-protection. It also shows a strong herd protection effect of vaccination. Reassuringly, there was no evidence of other non-vaccine types becoming more common. The results of this thesis will inform future decisions about changes to the National HPV Immunisation Programme and the UK Cervical Screening Programme

Performance of human papillomavirus DNA detection in residual specimens taken for Chlamydia trachomatis and Neisseria gonorrhoeae nucleic acid amplification testing in men who have sex with men

OBJECTIVES: Rectal swab specimens, either alone or pooled with first-void urine (FVU) and pharyngeal swab specimens, are used to test for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection in men who have sex with men (MSM). Following introduction of human papillomavirus (HPV) vaccination for MSM attending UK sexual health services (SHSs), HPV testing of residual CT/NG test specimens has been proposed to monitor HPV prevalence in this population. Performance of HPV detection in such specimens has not been evaluated previously. METHODS: MSM attending a UK SHS provided three specimens: (1) rectal swab for CT/NG, (2) pooled rectal/pharyngeal/FVU specimen for CT/NG and (3) dedicated anal swab for HPV. Specimen 3 and residual material from specimens 1 and 2 were tested for type-specific HPV DNA. HPV detection was by an in-house multiplex PCR and luminex-based genotyping assay. RESULTS: A total of 129 MSM were recruited with a mean age of 38.1 years; 24% were HIV-positive. Of the 129 MSM, 92 (71%) had any type-specific HPV DNA in ≥1 specimen; 80 (62%) had high risk (HR) HPV. Of 123 participants with sufficient residual pooled and dedicated specimens, 70 (56.9%) had detectable HPV on both, and 40 (32.5%) were negative on both; overall concordance was 89% (95% CI 83% to 94%), and kappa statistic was 0.78 (95% CI 0.66 to 0.89). Pooled samples had a 4.1% (95% CI -1.9% to 10.0%) higher test positivity rate than dedicated samples.Of 125 participants with sufficient residual rectal and specimens, 74 (59.2%) had detectable HPV on both, and 36 (28.8%) were negative on both; overall concordance was 88% (95% CI 81% to 93%), and kappa statistic was 0.74 (95% CI 0.61 to 0.86). Residual rectal samples had 5.6% (95%CI -0.6% to 11.8%) higher test positivity than dedicated samples. CONCLUSIONS: We observed high concordance between the dedicated and residual STI test specimens. Our data support the strategy of testing residual specimens for HPV prevalence monitoring in MSM to evaluate the impact of the targeted vaccination programme

Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England.

BACKGROUND: Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised. METHODS: Residual vulva-vaginal swab (VVS) specimens from young women aged 16-24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010-2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008. RESULTS: A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16-18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16-18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16-18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation. CONCLUSIONS: These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types

HPV self-sampling as an alternative strategy in non-attenders for cervical screening – a randomised controlled trial

BACKGROUND: A randomised trial to ascertain whether women who do not attend for cervical screening are more likely to respond to the opportunity to collect a self-sample for human papillomavirus (HPV) testing, or to a further invitation to attend for cervical screening.METHODS: The study was carried out in a Primary Care Trust (PCT) in London between June 2009 and December 2009. In total, 3000 women were randomly selected from persistent non-responders (i. e., who had not responded to at least two invitations to attend for screening). The women were randomised on a 1 : 1 basis to either receive an HPV self-sampling kit or a further invitation to attend for cervical cytology. The main outcome measures were (1) percentage of women attending for cervical cytology compared with those returning a self-sample HPV test or attending for cytology subsequent to receiving the kit and (2) percentage of those testing positive for HPV who attended further investigation.RESULTS: The total response in the self-sampling group for screening was 10.2%. Of the 1500 women in the control group sent a further invitation for cervical screening, 4.5% attended for cytology screening. This difference is highly statistically significant (Po0.0001). Of the 8 women who tested positive for HPV, 7 attended for a cervical smear and had a concurrent colposcopy. Three of these (43%) had high-grade disease (defined as CIN 2+), with one found to have an invasive cancer (stage 1b) and one CIN 3.CONCLUSIONS: The value of this intervention relies on the detection of high-grade CIN and early stage cancer with a good prognosis. The relatively high yield of abnormalities found is consistent with that expected among a hard to reach and relatively high-risk group of women. Our study suggests that self-sampling could increase participation among non-responders in England, but further work is needed to ascertain whether the low response rate seen here is likely to be representative of the rest of the country. Other studies are needed to investigate the response to self-sampling in different demographic and geographic settings. British Journal of Cancer (2011) 104, 915-920. doi: 10.1038/ bjc. 2011.48 www. bjcancer. co

Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important

Age-specific outcomes from the first round of HPV screening in unvaccinated women: Observational study from the English cervical screening pilot

Objective: To report detailed age-specific outcomes from the first round of an English pilot studying the implementation of high-risk human papillomavirus (HR-HPV) testing in primary cervical screening. Design: Observational study with screening in 2013–2016, followed by two early recalls and/or colposcopy until the end of 2019. Setting: Six NHS laboratory sites. Population: A total of 1 341 584 women undergoing screening with HR-HPV testing or liquid-based cytology (LBC). Methods: Early recall tests and colposcopies were recommended, depending on the nature of the screening-detected abnormality. Main outcome measures: We reported standard screening process indicators, e.g. proportions with an abnormality, including high-grade cervical intraepithelial neoplasia (CIN2+) or cancer, and the positive predictive value (PPV) of colposcopy for CIN2+, by screening test and age group. Results: Among unvaccinated women screened with HR-HPV testing at age 24–29 years, 26.9% had a positive test and 10.4% were directly referred to colposcopy following cytology triage, with a PPV for CIN2+ of 47%. At 50–64 years of age, these proportions were much lower: 5.3%, 1.2% and 27%, respectively. The proportions of women testing positive for HR-HPV without cytological abnormalities, whose early recall HR-HPV tests returned negative results, were similar across the age spans: 54% at 24–29 years and 55% at 50–64 years. Two-thirds of infections at any age were linked to non-16/18 genotypes. Among women with CIN2, CIN3 or cervical cancer, however, the proportion of non-16/18 infections increased with age. As expected, the detection of abnormalities was lower following screening with LBC. Conclusions: These data provide a reliable reference for future epidemiological studies, including those concerning the effectiveness of HPV vaccination. Tweetable abstract: Data from the English pilot study provide a comprehensive overview of abnormalities detected through HPV screening

Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial

This work was supported by a Cancer Research UK project grant (C8162/A4609 project costs) and a programme grant (C8162/A10406)