David Mesher

Cervical cytology is recommended by WHO as a triage option in HPV-based cervical cancer screening programmes. We assessed the performance of cytology to detect CIN3+ without and with knowledge of HPV positivity. Women were screened with cytology and HPV across ESTAMPA study centres in Latin America. Screen-positives were referred to colposcopy with biopsy and treatment as needed. Cytology was initially interpreted without knowing HPV results. A subset of cytologies from HPV-positive women were re-interpreted at the same laboratories, with knowledge of HPV status, blinded to previous cytology and histological diagnosis. Performance indicators for cytology to detect CIN3+ without and with knowledge of HPV positivity were estimated. A total of 4,087 women were included, of which 490 had histologically confirmed CIN3 + (455 CIN3 and 35 cancers). Cytology sensitivity without knowledge of HPV positivity for CIN3+ was 47.2% (95% CI: 42.5-51.9), whereas with knowledge of HPV positivity, the sensitivity was higher (58.9%, 95% CI: 54.2-63.5), p < .0001. The specificity without knowledge of HPV was 89.4% (95% CI: 88.2-90.5), while with knowledge of HPV positivity was 78.9% (95% CI: 77.4-80.4), p < .0001. Performance estimates varied by study centre for cytology without knowing the HPV positivity, (range from 32.8% to 61.5% for sensitivity; range 80.7% to 98.6% for specificity). Similarly, performance varied with knowledge of HPV positivity (36.1% to 93.4% for sensitivity; 39.6% to 98.6% for specificity). The increase in sensitivity of cytology with HPV knowledge was limited and highly variable, reinforcing the need for alternative triage methods to support cervical cancer elimination goals.

Background: In England, bivalent vaccination (Cervarix) against high-risk human papillomavirus (HR-HPV) genotypes 16/18 was offered in a population-based catch-up campaign in 2008–2010 to girls aged 14–17 years. These women are now entering the national cervical screening programme. We determined the impact of catch-up bivalent vaccination on their screening outcomes. Methods: We studied the overall and genotype-specific screening outcomes in 108,138 women aged 24–25 (offered vaccination) and 26–29 years (not offered vaccination) included in the English HPV screening pilot between 2013 and 2018. Results: At 24–25 years, the detection of high-grade cervical intraepithelial neoplasia (CIN2+) associated with HPV16/18 decreased from 3 to 1% (p < 0.001), with estimated vaccine effectiveness of 87% (95% CI: 82–91%). The detection of any CIN2+ halved from 6 to 3% (p < 0.001), with an estimated vaccine effectiveness of 72% (95% CI: 66–77%). The positive predictive value of a colposcopy for CIN2+ decreased for both low-grade (p < 0.001) and high-grade (p = 0.02) abnormalities on triage cytology. The decreases in screen-detected abnormalities at age 26-29 were of a substantially smaller magnitude. Conclusions: These data confirm high effectiveness of bivalent HPV vaccination delivered through a population-based catch-up campaign in England. These findings add to the rationale for extending screening intervals for vaccinated cohorts.

Objectives Men who have sex with men (MSM) have an increased risk of human papillomavirus (HPV) infection and related diseases compared with men who have sex exclusively with women. From April 2018, there has been a phased roll-out of HPV vaccination offered to MSM aged up to 45 years old who are attending sexual health clinics and HIV clinics in England. The vaccine is most effective if delivered prior to HPV infection. We estimated the proportion of MSM with no current vaccine-type infection and no serological evidence of prior infection, in a study undertaken prior to vaccine introduction. Methods We conducted a cross-sectional study among 484 MSM aged 18–40 years old who attended a sexual health clinic in London between 2010 and 2012. We estimated the prevalence of current and past infection by testing for HPV DNA in anogenital samples and for serum antibodies to HPV16 and HPV18. Results The median age was 30 years (IQR 25–35). The prevalence of HPV16 and HPV18 DNA was 13.2% and 6.2%, respectively. Seropositivity for HPV16 and HPV18 was 28.5% and 17.1%, respectively, with 11.4% seropositive for both types. Seropositivity for the same HPV type was strongly associated with anogenital DNA detection. 279 MSM (57.6%) tested negative for both HPV16 and HPV18 serology and were DNA negative for these two types; only 5 MSM (1.0%) were seropositive and DNA positive for both HPV types. Conclusions This is the first study to determine both the prevalence of HPV DNA in anogenital samples and HPV seroprevalence among MSM attending a sexual health clinic in the UK. Over half of MSM in this study had no evidence of a previous or current infection with either of the high-risk HPV types included in the quadrivalent vaccine, which supports the rationale for opportunistic HPV vaccination of MSM attending sexual health clinics.

Objectives: Rectal swab specimens, either alone or pooled with first-void urine (FVU) and pharyngeal swab specimens, are used to test forChlamydia trachomatis(CT) andNeisseria 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.

Background Human papillomavirus (HPV) vaccination for gay, bisexual and other men who have sex with men (GBMSM) aged up to 45 years attending sexual health clinics (SHC) and HIV clinics began in England as a pilot in June 2016, with national roll-out from April 2018. The recommended course is three doses of the quadrivalent HPV vaccine over one to 2 years. We present the methodology and results of monitoring vaccination uptake (initiation and completion), and attendance patterns, during the pilot phase. Methods Total numbers of eligible GBMSM receiving HPV vaccine doses were extracted from routine datasets from pilot start to end of March 2018. Numbers of attendances since January 2009 were extracted and tested for trends before and after introduction of HPV vaccination. Results Overall, first dose uptake was 49.1 % (23 619/48 095), with clinics with highest data completeness achieving close to 90% uptake during the pilot period. Refusals were very low (3.5%). There was no evidence of increases in the number of GBMSM attendances at pilot SHC. Conclusions HPV vaccination has not caused important deviations to expected attendance patterns of GBMSM at SHC throughout the pilot phase. Overall, recorded initiation has been encouraging given known issues with data recording, as is current status of second and third dose completion. Attendances, vaccination initiation and completion will continue to be monitored alongside surveillance of anogenital warts diagnoses and of rectal HPV prevalence.

Background: Opportunistic human papillomavirus (HPV) vaccination for men who have sex with men (MSM) was piloted in sexual health clinics (SHC) in England between 2016 and 2018. Aim: to evaluate the pilot’s first year (April 2016–March 2017) in terms of feasibility, acceptability, uptake, impact and equity and interpret the outcome in the context of wide HPV vaccination policy. Methods: Attendance and uptake data from routine SHC surveillance datasets and a cross-sectional survey administered to individuals receiving the vaccine were analysed. Results: Among 18,875 eligible MSM, 8,580 (45.5%) were recorded as having received one HPV vaccine dose, decreasing slightly with increasing age, and uptake was higher in rural than urban areas. Survey results suggested that of those receiving the first dose of HPV vaccine, 8% were new attendees and that among those, less than 11% attended just to receive the vaccine. Of those having their first HPV vaccination, 95% indicated they would like to receive the next vaccine doses at the same clinic and 85% of patients reported accessing other services when visiting SHC for the first dose of vaccine. Conclusion: An opportunistic HPV vaccination programme for MSM can be delivered in an acceptable and, as far as can be evaluated, equitable manner, without major disruption to SHC and HIV clinics.

Objectives In 2008, a national human papillomavirus (HPV) vaccination programme for females was introduced in England using the bivalent vaccine (HPV16 and 18 only). In 2012, the programme changed to offer the quadrivalent vaccine that includes protection against the two HPV types that cause the majority of anogenital warts (AGW; HPV6 and 11). We present data reporting AGW diagnoses in sexual health clinics (SHCs) in England to the end of 2017, including diagnoses among birth cohorts offered the quadrivalent vaccine. Methods Using data from all SHCs across England, we performed ecological analyses to consider rates of AGW diagnoses by age, gender and sexual orientation. We tested for trends over time of diagnoses of AGW in young females, heterosexual males, and men who have sex with men (MSM) between the ages of 15 and 24 years during both bivalent (2009 to 2013) and quadrivalent (2014 to 2017) vaccine time periods using Poisson regression. Results Between 2014 and 2017, there was strong evidence for a decreasing trend in the rate of AGW diagnoses at SHC among females aged 15–17 years from 257.5 to 45.7 per 100 000 population (82.3% decline) and same aged heterosexual males from 59.1 to 19.1 per 100 000 population (67.7% decline). The reductions in the incidence of AGW diagnoses in MSM aged 15–17 years were less clear (decreased by 13.6% between 2014 and 2017, from 129.9 to 112.2 per 100 000 population). Conclusions The moderate, unexpected declines in AGW seen since the introduction of a high-coverage HPV vaccination programme using the bivalent vaccine are being followed, as expected, by much larger declines among females offered the quadrivalent vaccine and same-aged heterosexual males. Surveillance plans are in place to continue to monitor AGW diagnoses to evaluate the impact of both female and targeted MSM HPV vaccination on early disease outcomes.