Bivalent Vaccine Effectiveness Against Anal Human Papillomavirus Positivity Among Female Sexually Transmitted Infection Clinic Visitors in the Netherlands.

Human papillomavirus (HPV) vaccines are indicated for anal cancer prevention, but evidence for vaccine effectiveness (VE) against anal HPV infections among women is limited. We estimated the VE (≥1 dose) against anal HPV positivity of the bivalent vaccine, whose target types HPV-16/18 are associated with approximately 90% of HPV-related anal cancers. Among 548 female STI clinic visitors 16-24 years old who provided an anal swab sample as part of a repeated cross-sectional survey, VE against HPV-16/18 was 89.9% (95% confidence interval, 63.0%-97.2%). Type-specific VE correlated well with VE against cervicovaginal HPV (Spearman ρ = 0.76), suggesting comparable effectiveness of HPV-16/18 vaccination against genital and anal infections.

Evidence for Missing Positive Results for Human Papilloma Virus 45 (HPV-45) and HPV-59 with the SPF10-DEIA-LiPA25 (Version 1) Platform Compared to Type-Specific Real-Time Quantitative PCR Assays and Impact on Vaccine Effectiveness Estimates.

Human papillomavirus (HPV) epidemiological and vaccine studies require highly sensitive HPV detection systems. The widely used broad-spectrum SPF10-DEIA-LiPA25 (SPF10 method) has reduced sensitivity toward HPV-45 and -59. Therefore, anogenital samples from the PASSYON study were retrospectively analyzed with type-specific (TS) HPV-45 and -59 real-time quantitative PCR (qPCR) assays. The SPF10 method missed 51.1% of HPV-45 and 76.1% of HPV-59 infections that were detected by the TS qPCR assays. The viral copy number (VCn) of SPF10-missed HPV-45 and -59 was significantly lower than SPF10-detected HPV-45 and -59 (P < 0.0001 for both HPV types). Sanger sequencing showed no phylogenetic distinction between SPF10-missed and SPF10-detected HPV-59 variants, but variants bearing the A6562G single-nucleotide polymorphism (SNP) in the SPF10 target region were more likely to be missed (P = 0.0392). HPV cooccurrence slightly influenced the detection probability of HPV-45 and -59 with the SPF10 method. Moreover, HPV-59 detection with the SPF10 method was hampered more in nonvaccinated women than vaccinated women, likely due to a stronger masking effect by increased HPV cooccurrence in the former group. Consequently, the SPF10 method led to a strong negative vaccine effectiveness (VE) of -84.6% against HPV-59, while the VE based on TS qPCR was 3.1%. For HPV-45, the relative increase in detection in nonvaccinated women compared vaccinated women was more similar, resulting in comparable VE estimates. In conclusion, this study shows that HPV-45 and -59 detection with the SPF10 method is dependent on factors including VCn, HPV cooccurrence, and vaccination, thereby showing that knowledge of the limitations of the HPV detection method used is of great importance.

Assessment of herd effects among women and heterosexual men after girls-only HPV16/18 vaccination in the Netherlands: A repeated cross-sectional study.

Data on the impact of human papillomavirus (HPV) vaccination on the population HPV prevalence are largely obtained from women. We assessed the impact of the girls-only HPV16/18 vaccination program in the Netherlands that started in 2009, on trends in HPV prevalence among women and heterosexual men, using data from the PASSYON study. In this cross-sectional study, the HPV prevalence among 16- to 24-year-old visitors to sexually transmitted infection clinics was assessed in 2009, 2011, 2013, and 2015. We compared the genital postvaccination HPV prevalence with the prevaccination prevalence (2009) using Poisson GEE models. In total, we included 4,996 women and 1,901 heterosexual men. The percentage of women who reported to be vaccinated increased from 2.3% in 2009 to 37% in 2015. Among all women, the HPV16/18 prevalence decreased from 23% prevaccination to 15% in 2015 (adjusted prevalence ratio [aPR] 0.62, ptrend < 0.01). Among heterosexual men, the HPV16/18 prevalence decreased from 17% prevaccination to 11% in 2015 (aPR 0.52, ptrend < 0.01). Of the heterosexual men with a steady partner, HPV16/18 prevalence was lower among those whose steady partner had been vaccine-eligible in the national immunization program (aPR 0.13). Among unvaccinated women, the HPV16/18 prevalence in 2015 was not different from prevaccination. The decreasing HPV16/18 prevalence among heterosexual men and the reduced HPV16/18 prevalence among heterosexual men with a vaccine-eligible steady partner strongly suggests herd protection from girls-only vaccination. Absence of notable herd effects among unvaccinated women 6 years postvaccination may be due to the moderate vaccine uptake among girls in the Netherlands.

Bivalent Vaccine Effectiveness Against Type-Specific HPV Positivity: Evidence for Cross-Protection Against Oncogenic Types Among Dutch STI Clinic Visitors.

Background: Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estimated VE from the bivalent human papillomavirus (HPV) vaccine against HPV positivity of vaccine and nonvaccine types in a high-risk population. Methods: We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional survey in Dutch sexually transmitted infection clinics. Vaginal swabs were analyzed using a polymerase chain reaction-based assay (SPF10-LiPA25) able to detect the 12 high-risk HPV (hrHPV) types 16/18/31/33/35/39/45/51/52/56/58/59. We compared hrHPV positivity between self-reported vaccinated (≥1 dose) and unvaccinated women, and estimated VE by a logistic mixed model. Results: We included 1087 women of which 53% were hrHPV positive and 60% reported to be vaccinated. The adjusted pooled VE against HPV-16/18 was 89.9% (81.7%-94.4%). Moreover, we calculated significant VE against nonvaccine types HPV-45 (91%), HPV-35 (57%), HPV-31 (50%), and HPV-52 (37%). Among women who were offered vaccination 5/6 years ago, we estimated similar VE against HPV-16/18 (92%) and all hrHPV types (35%) compared to women who were offered vaccination <5 years ago (83% and 33%, respectively). Conclusion: We demonstrated high VE of the bivalent vaccine against HPV-16/18 and cross-protection against HPV-45/35/31/52. Protection against HPV-16/18 was sustained up to 6 years postvaccination.

HPV infections among young MSM visiting sexual health centers in the Netherlands: Opportunities for targeted HPV vaccination.

INTRODUCTION: In 2009, girls-only HPV16/18 vaccination was introduced in the Netherlands which has achieved 46-61% uptake. Heterosexual men have benefitted from herd protection, but it is unknown whether men who have sex with men (MSM) also benefit from herd effects of the girls-only HPV16/18 vaccination program. Because MSM bear a high HPV-related disease burden, countries might consider targeted vaccination for MSM. To study possible herd effects and prior HPV exposure at a potential moment of vaccination, we assessed trends in the HPV prevalence and proportions (sero)negative for the various vaccine types among young MSM visiting sexual health centers (SHCs). METHODS: We used data from MSM included in PASSYON study years 2009-2017. In this biennial cross-sectional study among visitors of SHCs aged 16-24 years, MSM provided a penile and anal swab for HPV DNA testing (including vaccine types HPV6/11/16/18/31/33/45/52/58) and blood for HPV antibody testing (HPV16/18/31/33/45/52/58). RESULTS: In total 575 MSM were included, with a median of 22 years of age and 15 lifetime sex partners and 3.5% HIV positive. Trends in penile or anal HPV prevalence during 2009-2017 were statistically non-significant for all vaccine types. Of the 455 MSM with a penile and anal swab, 360 (79%), 283 (62%) and 242 (53%) were HPV DNA negative at both anatomical sites for HPV16/18, HPV6/11/16/18 and HPV6/11/16/18/31/33/45/52/58 respectively. Among MSM who were HPV16/18 and HPV16/18/31/33/45/52/58 DNA negative and were tested for serology (n = 335 and 279 respectively), 82% and 71% were also seronegative for the respective types. DISCUSSION: There were no significant declines in the HPV prevalence among MSM up to eight years after introduction of girls-only HPV16/18 vaccination, indicating that MSM are unlikely to benefit largely from herd effects from girls-only vaccination. Most MSM were vaccine-type DNA negative and seronegative, suggesting that vaccination of young MSM visiting SHCs could still be beneficial.

No evidence for cross-protection of the HPV-16/18 vaccine against HPV-6/11 positivity in female STI clinic visitors.

OBJECTIVES: Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11 positivity and AGW in the Netherlands. METHODS: We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional study among 16- to 24-year-old sexually transmitted infection (STI) clinic attendants. Vaginal self-swabs were analyzed for type specific HPV and AGW were diagnosed at the STI-clinic. Prevalence of HPV-6 and/or HPV-11 and AGW were compared between self-reported vaccinated and unvaccinated women by log-binomial regression analysis, adjusted for demographics and risk behavior. RESULTS: Of the 1198 women included, 56% reported to be vaccinated at least once. Relative to unvaccinated women, the adjusted prevalence ratio (PR) for HPV-6/11 was 1.03 (95% confidence interval [CI] 0.74-1.43) for women vaccinated at least once. The crude PR for AGW was 0.67 (95% CI 0.22-2.07) for women vaccinated at least once. Adjustment did not change these results. CONCLUSIONS: We observed no cross-protective effect of the bivalent vaccine on genital HPV-6/11 positivity and a non-significant partially protective effect on AGW.