POTENTIAL BENEFITS OF SECOND-GENERATION VACCINES AGAINST HUMAN PAPILLOMAVIRUS (HPV)

Purpose: Current prophylactic vaccines against human papillomavirus (HPV) target two high-risk types (16 and 18) that contribute to roughly 70% of cervical cancer cases worldwide. Our objective was to quantify the range of additional benefits conferred by second-generation HPV prophylactic vaccines that are expected to include protection against five additional high-risk types (31, 33, 45, 52 and 58).

Method: A microsimulation model of HPV and cervical cancer calibrated to epidemiological data from two countries (Kenya and Uganda) was used to estimate the reductions in lifetime risk of cervical cancer from the second-generation HPV vaccines. We explored the absolute and relative importance of certain characteristics of the population (i.e., distribution of HPV types in cancer, the prominence of co-infection with multiple HPV types or unidentifiable HPV types, existence of a cervical cancer screening program) and the vaccine (i.e., cross-protective effects against non-targeted HPV types, vaccine uptake), and evaluated the comparative effectiveness of these future HPV vaccines against currently-available vaccines.

Result: Assuming no screening and complete uptake of the second-generation vaccine, reduction in lifetime cancer risk was 86.33% in Kenya and 91.83% in Uganda, representing an absolute increase in cervical cancer reduction of 26.13% in Kenya and 17.92% in Uganda, compared with complete uptake with the current vaccines. This increase in benefits rose to 29.10% in Kenya and 19.48% in Uganda when assuming the extreme case that cancers with co-infected and unidentifiable HPV types are attributable to one of the five new types covered in the second-generation vaccine. In contrast, when assuming cases with multiple HPV infections or unidentified types are not attributable to one of the five new types, additional absolute benefits in cancer prevention dropped to 19.60% in Kenya and 13.99% in Uganda. Allowing for vaccine cross-protection in both the current and second-generation vaccines, these effects were blunted in both countries. Vaccine uptake and screening 1-3 times per lifetime had relatively smaller effects on the added benefit of the second-generation vaccines. 

Conclusion: Second-generation HPV vaccines that extend protection to additional HPV types have the potential to improve cervical cancer prevention. Multiple HPV infections and unidentifiable HPV types can influence vaccine effectiveness, but their impacts may be moderated by vaccine cross-protective effects. These benefits must be weighed against the cost of the vaccines in future analyses.