Vaccination against cancer-associated strains of human papillomavirus (HPV) could be highly effective at preventing pre-cancerous anal cell changes in men living with HIV, according to research published in the online edition of the Journal of Infectious Diseases.
The cross-sectional study showed that almost all cases of high-grade anal intraepithelial neoplasia (HGAIN) – the cell changes that occur in the anus prior to the development of anal cancer – were caused by strains of HPV covered by licensed or investigational vaccines. The investigators believe their findings “can inform assumptions of HPV vaccine efficacy and cost-effectiveness and decision-analysis models.”
There is a high incidence and prevalence of pre-cancerous anal lesions and anal cancer in HIV-positive gay men. Vaccines that provide a high level of protection against the HPV genotypes with the highest risk of anal and genital cancers have been licensed. Research is currently underway into potential vaccines that provide even broader protection. HPV vaccination is currently targeted at adolescent girls. There has been considerable debate about the efficacy and cost-effectiveness of vaccinating adult, HIV-positive gay men.
Doctors in San Francisco therefore designed a study involving 363 HIV-positive gay men who received care between 2009 and 2010. Each patient was screened for the presence of pre-cancerous anal lesions and provided samples for HPV genotyping. Several HPV genotypes have been associated with pre-cancerous anal cell changes. These include HPV 16/18/31/33/45/52/58. These genotypes are covered by licensed or investigational vaccines.
Multiple HPV genotypes are often present in pre-cancerous lesions. The investigators therefore developed a model that allowed them to calculate the proportion of cases of HGAIN attributable to individual HPV genotypes. “We used this information to predict the potential efficacy of prophylactic HPV vaccines, under the assumption that vaccination would occur before natural infection and seroconversion,” explain the authors.
The study participants had a median age of 53 years. They were highly sexually experienced. The median age at first anal sex was 20 years; 40% reported over 40 lifetime anal sex partners; and 15% reported three or more partners for anal sex within the previous six months. The majority (94%) were taking antiretroviral therapy. Approximately three-quarters (72%) had a CD4 cell count above 350 cells/mm3 and 90% had an undetectable viral load.
The majority of the patients (59%) had pre-cancerous anal lesions, including 30% with HGAIN. Three-quarters of individuals were infected with a high-risk HPV genotype. HPV16 was the most common individual genotype, present in 28% of patients.
“HPV16, which has been shown to cause an even greater proportion of anal cancers than cervical cancers, is seen as the dominant genotype in HGAIN disease categories,” write the authors. “Other HPV genotypes vary substantially in their prevalence and attribution estimates in our study.”
The prevalence of high-risk HPV genotypes increased significantly according to the severity of pre-cancerous anal lesions (p < 0.05). Patients with more severe disease were also significantly more likely to be infected with multiple high-risk HPV genotypes. Up to seven individual high-risk genotypes were identified in individual lesions.
Depending on the number of infecting HPV genotypes, the proportion of cases of HGAIN attributed to HPV16/18 and other individual genotypes covered by currently licensed vaccines ranged between 12 and 62%. The fraction of cases attributed to the individual genotypes targeted by investigational vaccines ranged between 39 and 89%.
Taken together, 95% of all high-grade lesions were attributed to high-risk genotypes. The licenced quadrivalent vaccine covered 71% of genotypes present in the highest-grade lesions, whereas the investigational nonavalent vaccine would have provided protection against 89% of HPV genotypes in high-grade lesions.
“The prevention of anal cancer in high-risk populations such as HIV-infected MSM [men who have sex with men] remains an urgent priority,” conclude the investigators. “The analytical framework presented in this study can be applied to larger and pooled efforts to improve estimations of the causative role of individual genotypes and expand our understanding of the natural history of and prevention approaches for anal neoplastic disease.”
Sahasrabuddhe VV et al. Human papillomavirus genotype attribution and estimation of preventable fraction of anal intraepithelial neoplasia cases among HIV-infected men who have sex with men. J Infect Dis, online edition. DOI: 10.1093/infdis/jis694, 2013.