Potential effectiveness of prophylactic HPV immunization for men who have sex with men in the Netherlands: A multi-model approach

Abstract

Background

Men who have sex with men (MSM) are at high risk for anal cancer, primarily related to human papillomavirus genotype 16 (HPV16) infections. At 8.5 per 100,000 per year, the incidence rate of anal cancer among MSM is similar to that of cervical cancer among adult women in the Netherlands. However, MSM are not included in most HPV vaccination programs. We explored the potential effectiveness of prophylactic immunization in reducing anogenital HPV16 transmission among MSM in the Netherlands.

Methods and findings

We developed a range of mathematical models for penile–anal HPV16 transmission, varying in sexual contact structure and natural history of infection, to provide robust and plausible predictions about the effectiveness of targeted vaccination. Models were informed by an observational cohort study among MSM in Amsterdam, 2010–2013. Parameters on sexual behavior and HPV16 infections were obtained by fitting the models to data from 461 HIV-negative study participants, considered representative of the local MSM population. We assumed 85% efficacy of vaccination against future HPV16 infections as reported for HIV-negative MSM, and age-specific uptake rates similar to those for hepatitis B vaccination among MSM in the Netherlands. Targeted vaccination was contrasted with vaccination of 12-year-old boys at 40% uptake in base-case scenarios, and we also considered the effectiveness of a combined strategy. Offering vaccine to MSM without age restrictions resulted in a model-averaged 27.3% reduction (90% prediction interval [PI] 11.9%–37.5%) in prevalence of anal HPV16 infections, assuming similar uptake among MSM as achieved for hepatitis B vaccination. The predicted reduction improved to 46.1% (90% PI 21.8%–62.4%) if uptake rates among MSM were doubled. The reductions in HPV16 infection prevalence were mostly achieved within 30 years of a targeted immunization campaign, during which they exceeded those induced by vaccinating 40% of preadolescent boys, if started simultaneously. The reduction in anal HPV16 prevalence amounted to 74.8% (90% PI 59.8%–93.0%) under a combined vaccination strategy. HPV16 prevalence reductions mostly exceeded vaccine coverage projections among MSM, illustrating the efficiency of prophylactic immunization even when the HPV vaccine is given after sexual debut. Mode of protection was identified as the key limitation to potential effectiveness of targeted vaccination, as the projected reductions were strongly reduced if we assumed no protection against future infections in recipients with prevalent infection or infection-derived immunity at the time of immunization. Unverified limitations of our study include the sparsity of data to inform the models, the omission of oral sex in transmission to the penile or anal site, and the restriction that our modeling results apply primarily to HIV-negative MSM.

Conclusions

Our findings suggest that targeted vaccination may generate considerable reductions in anogenital HPV16 infections among MSM, and has the potential to accelerate anal cancer prevention, especially when combined with sex-neutral vaccination in preadolescence.

Abstract

Johannes Bogaards and colleagues reveal the benefits of including men who have sex with men in a HPV vaccination program to reduce incidence of anal cancer.

Author summary

Why was this study done?

• Anal and genital human papillomavirus (HPV) infections are sexually transmitted and may cause cancer in the anogenital area.

• HPV vaccines protect against cancer by lowering the risk of getting infected with HPV, and are especially effective when given before becoming sexually active.

• Men who have sex with men (MSM) are at high risk for anal cancer, but are not included in most HPV vaccination programs.

• Decisions about their inclusion need to be informed by transmission models, but this is a challenge due to uncertainties regarding vaccine efficacy in those already exposed to HPV, and regarding HPV infection dynamics among MSM.

What did the researchers do and find?

• To give robust and plausible predictions about the effectiveness of targeted vaccination, we developed various models for HPV transmission among MSM that were parameterized using data from a Dutch cohort study.

• We assessed the effectiveness of various vaccination strategies targeting MSM or 12-year-old boys or a combination thereof, and assuming vaccine uptake in targeted campaigns comparable to that of hepatitis B vaccine among MSM in the Netherlands.

• In the models, targeted vaccination reduced the occurrence of anogenital HPV infections by around 30% after 40 years, with a range from 10% to 50%, depending on the recruitment of MSM into targeted campaigns and on the assumed mode of vaccine protection.

• This figure increased to 75% after 60 years when targeted vaccination was combined with sex-neutral vaccination in preadolescence, assuming 40% uptake among 12-year-old boys and 85% efficacy against future HPV16 infections in MSM.

What do these findings mean?

• Our results are helpful for prioritizing male HPV vaccination, especially when deciding on the implementation of a selective campaign among MSM.

• Offering HPV vaccine to sexually experienced MSM need not impede the efficiency of targeted vaccination, if vaccination protects against future HPV16 infections.

• Targeted vaccination deserves consideration, at least temporarily, to protect adult MSM at high risk for anal cancer.