Abstract

The human papillomavirus (HPV) vaccines may provide some level of cross-protection against high-risk HPV genotypes not directly targeted by the vaccines. We evaluated the long-term health and economic impacts of routine HPV vaccination using either the nonavalent HPV vaccine or the bivalent HPV vaccine in the context of 48 Gavi-eligible countries. We used a multi-modeling approach to compare the bivalent with or without cross-protection and the nonavalent HPV vaccine. The optimal, that is, most cost-effective, vaccine was the vaccine with an incremental cost-effectiveness ratio below the per-capita gross domestic product (GDP) for each country. By 2100 and assuming 70% HPV vaccination coverage, a bivalent vaccine without cross-protection, a bivalent vaccine with favorable cross-protection and the nonavalent vaccine were projected to avert 14.9, 17.2 and 18.5 million cumulative cases of cervical cancer across all 48 Gavi-eligible countries, respectively. The relative value of the bivalent vaccine compared to the nonavalent vaccine increased assuming a bivalent vaccine conferred high cross-protection. For example, assuming a cost-effectiveness threshold of per-capita GDP, the nonavalent vaccine was optimal in 83% (n = 40) of countries if the bivalent vaccine did not confer cross-protection; however, the proportion of countries decreased to 63% (n = 30) if the bivalent vaccine conferred high cross-protection. For lower cost-effectiveness thresholds, the bivalent vaccine was optimal in a greater proportion of countries, under both cross-protection assumptions. Although the nonavalent vaccine is projected to avert more cases of cervical cancer, the bivalent vaccine with favorable cross-protection can prevent a considerable number of cases and would be considered a high-value vaccine for many Gavi-eligible countries.

Highlights

  • Persistent infections with high-risk human papillomavirus, primarily HPV genotypes 16 and 18, cause most cervical cancer cases worldwide.[1]

  • The quadrivalent and nonavalent HPV vaccines protect against two low-risk HPV genotypes (HPV-6 and HPV-11), responsible for approximately 90% of genital warts

  • We expanded our singlecountry analysis performed in Uganda[17] to capture the potential vaccination impacts among women in all 48 low- and middle-income countries (LMIC) eligible for Gavi funding in 2018. As both the Harvard-HPV and Harvard-CC models require highly-detailed data on sexual behavior and cervical cancer epidemiology that are limited in most Gavi-eligible countries, we relied on a mapping process to extend the existing, calibrated Harvard-HPV and Harvard-CC models to project the burden of cervical cancer under alternative HPV vaccination scenarios in each of the individual 48 Gavi-eligible countries (Supporting Information Section S1)

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Summary

| INTRODUCTION

Persistent infections with high-risk human papillomavirus (hrHPV), primarily HPV genotypes 16 and 18, cause most cervical cancer cases worldwide.[1]. All three HPV vaccines confer high protection against vaccine-targeted HPV genotypes,[5,6,7,8,9] but there is growing evidence from vaccine trials and postimplementation evaluations that suggest the bivalent and quadrivalent vaccines may provide some additional level of cross-protection against high-risk HPV genotypes not directly targeted by the vaccines. The level of cross-protection varies with vaccine type, HPV genotype and study.[10,11,12,13] In particular, the bivalent vaccine has demonstrated greater cross-protection than the quadrivalent vaccine,[10] primarily against HPV-31, HPV-33 and HPV-45, which account for approximately 13% of cervical cancer cases. The five additional HPV genotypes directly protected by the nonavalent vaccine (HPV-31/33/45/52/58) account for approximately 18% of cervical cancers. Our objective was to evaluate the long-term health and economic impacts of routine HPV vaccination using either the nonavalent or the bivalent HPV vaccines with alternative cross-protective assumptions in the context of 48 Gavi-eligible countries

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