The systematic review and meta-analysis by Lissouba and colleagues adds to mounting data showing a strong association between genital human papillomavirus (HPV) infection and the risk of HIV acquisition, with an estimated summary odds ratio of 2.0 (95% confidence interval 1.6 to 2.5) for HIV acquisition associated with any-HPV infection. The strongest reported estimates are specific to clearance of HPV infection, suggesting that the association between HPV and HIV acquisition may not be fully attributable to confounding by other sexually transmitted infections (STIs) or co-transmission.1 ,2 Since prophylactic HPV vaccination is protective against HPV-16 and HPV-18, it is not surprising that six out of seven articles included in the Lissouba review commented on the potential use of HPV vaccination as a means to reduce HIV acquisition. A recent editorial has recommended the implementation of a randomised controlled trial (RCT).3

A concomitant reduction in HIV incidence following widespread prophylactic HPV vaccination would be a welcome additional benefit. There are, however, several important considerations. Previous RCTs have not consistently observed reductions in HIV acquisition following STI treatment and suppression, despite treatment efficacy and plausible biological mechanisms. Current generation HPV vaccines target only a subset of HPV infections, and in populations at high-risk for HIV, up to 80% of individuals with vaccine-preventable HPV types are coinfected with non-vaccine-preventable HPV types.4 While observational studies show an increase in HIV risk with an increasing number of HPV infections,1 ,5 suggesting that the vaccine may lower the risk of HIV by reducing the overall burden of HPV infection, most individuals will still be infected with other HPV genotypes and STIs such as herpes simplex virus type 2 even after HPV vaccination. In the context of multiple genital tract coinfections not targeted by current (or even future) HPV vaccines, the true population-level effect of HPV vaccination on HIV acquisition may be minimal.

Taken together, the value of large and expensive RCTs designed to evaluate the protective efficacy of HPV vaccination against HIV acquisition is questionable. The GAVI Alliance (formerly the Global Alliance for Vaccines and Immunisation) now fortunately supports HPV vaccination in specific resource-limited countries. Large scale roll-out of HPV vaccination in HIV endemic areas and targeted surveillance to monitor HIV incidence in pre-HPV and post-HPV vaccine eras may represent a more ethical and cost-effective alternative to RCTs.