Response to letter: limitations of human papillomavirus DNA testing in measuring previous exposure and vaccine protection.

Abstract

We thank Brown for his interest and comments regarding our published research findings 1. Documenting the molecular epidemiology of human papilloma virus (HPV) infection in men and in particular high-risk groups such as men who have sex with men (MSM) and HIV-infected MSM is of increasing importance. Such information will inform models which can estimate the effect of universal and targeted male HPV vaccination (either quadrivalent or nanovalent). Our study reports a high prevalence of any anal HPV DNA and of three oncogenic or high-risk (HR) HPV types (16, 18 and 31) in MSM in Dublin, Ireland. The prevalence of HPV infection described throughout the paper is referred to on one occasion as ‘incidence’ in the Discussion. The authors regret this error and have submitted an erratum to the Editors as clarification. We report a high prevalence of any anal HPV DNA (69%) and HR HPV types 16 (27%), 18 (16%) and 31(23%) in HIV-infected (n = 99) and HIV-negative (n = 95) MSM. These findings are comparable to those of other studies undertaken in MSM and HIV-infected MSM 2, 3. Fourteen study participants (12 of whom were HIV-infected) reported no sexual contacts in the preceding 12 months. Nine of 14 (64%) had HPV DNA detected and seven (50%) had at least one HR HPV type [16 (n = 5), 18 (n = 5) or 31 (n = 2)] detected. We acknowledge in our discussion that we cannot comment reliably on persistence of HPV infection given that our study is a point prevalence study; however, we believe that this is an important observation and warrants inclusion in our discussion. To further investigate the persistence of anal HPV infection, we prospectively followed a subgroup of 45 HIV-infected MSM [mean age (± standard deviation) 45 ± 12 years] who had anal HPV DNA detected in our published study 1. Participants were rescreened for anal HPV infection 6 months following initial screening. Forty-nine per cent had persistence of any anal HPV DNA, 33% had persistence of HPV-16, and 36% had persistence of HPV-18 at 6 months 4. The HIM study (which excluded HIV-positive participants) reported a much lower persistence of HPV-16 infection (5.1% n = 8) in MSM 5. Persistence of anal HPV infection has been shown to be higher in HIV-infected MSM 6, 7, as was observed in our study, and this likely contributes to the higher burden of anal cancers observed in this group 8. The natural history of HPV infection, persistence and clearance remains poorly understood and is difficult to elicit accurately given the many potential modes for infection, reinfection and indeed the reactivation of latent virus. In addition, sexual histories provided by study participants are frequently inaccurate 9. Longitudinal prospective studies pairing type-specific HPV DNA detection at multiple sites with type-specific serum HPV antibodies for multiple oncogenic HPV types such as the H2M study and the SPANC study will provide further insights into the natural history and prevention of HPV infection and HPV-associated disease in MSM. The quadrivalent HPV vaccine (6, 11, 16 and 18) has been shown to be highly effective in preventing vaccine type HPV infection in men 10. A number of studies have reported the potential of HPV vaccine to prevent development of HPV-associated disease in older MSM 11-13. Although no therapeutic benefit of the HPV vaccine has been demonstrated for the treatment of active disease present at the time of vaccination, emerging data suggest a possible benefit of HPV vaccination in the setting of previous disease 14. Cost effectiveness of the quadrivalent HPV vaccine has been demonstrated in models looking at specific “at-risk” populations such as MSM over a range of assumptions 15. The recently available nanovalent HPV vaccine offers protection against an additional five oncogenic HPV types (31, 33, 45, 52 and 58) associated with anal cancers 16, 17. HPV vaccination of boys and male adolescents is not yet recommended in Ireland or in the majority of European countries which offer HPV vaccination of girls through national immunization programmes because of a lack of cost-effectiveness data. Universal vaccination of boys and girls offers the greatest preventative potential; however, this strategy would have no effect on risk of HPV-associated disease in current adult populations. Reported anal HPV DNA prevalence varies widely 18 and has been shown to be associated with a number of factors including age, smoking status, sexual behaviours and geographical location 1-3. Local prevalence data are important from an individual, national and international perspective and will greatly inform policy makers in relation to vaccination strategies. Targeted HPV vaccine has potential to greatly reduce the increasing burden of HPV-associated anal cancer in high-risk populations such as MSM and HIV-infected MSM in the future. Evidence suggests that acceptability of HPV vaccine would be high in such groups 19 and vaccine should not be withheld.