Efficacy and Herd Effects of HPV Vaccination Programs

An updated systematic review and meta-analysis of the efficacy of HPV vaccines revealed compelling evidence for the considerable effect of HPV vaccination programs on HPV infections and cervical intraepithelial neoplasia grade 2+ (CIN2+) among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. The review, published in The Lancet, included data from 60 million individuals and up to 8 years of post-vaccination follow-up.

Embase and MEDLINE searches turned up 1702 eligible articles published between February 2014 and October 2018. Included in these were 65 articles from 14 high-income countries, 23 of which investigated HPV infection, 29 anogenital warts, and 13 investigated CIN2+.

In the 5 to 8 years following the introduction of HPV vaccines, the prevalence of HPV 16 and 18 decreased significantly by 83% among girls aged 13 to 19 years and women aged 20 to 24 years (relative risk [RR] 0.17; 95% CI, 0.11-0.25) and 66% (RR, 0.34; 95% CI, 0.23-0.49), respectively. Prevalence of HPV 31, 33, and 45 also decreased significantly by 54% (RR, 0.46; 95% CI, 0.33-0.66) among girls aged 13 to 19 years. Diagnoses of anogenital warts dropped significantly by 67% (RR, 0.33; 95% CI, 0.24-0.46) among girls aged 15 to 19 years, by 54% (RR, 0.46; 95% CI, 0.36-0.60) among women aged 20 to 24 years, and by 31% (RR, 0.69; 95% CI, 0.53-0.89) among women aged 25 to 29 years. In boys aged 15 to 19 years, anogenital warts diagnoses decreased significantly by 48% (RR, 0.52; 95% CI, 0.37-0.75) and by 32% (RR, 0.68; 95% CI, 0.47-0.98) among men aged 20 to 24 years.

Among the girls aged 15 to 19 years and women aged 20 to 24 years, investigators observed that CIN2+ decreased significantly in the period of 5 to 9 years after vaccination by 51% (RR, 0.49; 95% CI, 0.42-0.58) and 31% (RR, 0.69; 95% CI, 0.57-0.84), respectively.

Investigators noted that CIN2+ surveillance data should to be interpreted with caution as the largest and fastest reductions were observed in the cohort between age 15 and 19 years, an age group not generally recommended for screening and in which the percentage of patients screened is declining.  Further, it has been shown that participation in cervical screening and vaccination uptake are associated with the same sociodemographic factors, meaning that in some settings coverage among screened individuals may be different and possibly higher compared with country-level and regional-level vaccination coverage. In addition, there have been recent changes in screening recommendations, clinical management recommendations, and participation documented in several countries surrounding the introduction of vaccines.

Caution is also recommended in interpretation of the results due to several study limitations, including that causality between HPV vaccination and the observed changes in HPV-related end points cannot be concluded definitively. In addition, the number of studies available for each HPV-related end point was too small for a multivariate meta-regression analyses that simultaneously considered the influence of different program characteristics or study designs. Further, the number of studies available in each category was limited and all studies identified in the systematic review were from high-income countries.

Investigators concluded that their results, “show compelling evidence of the substantial [effect] of three dose girls-only HPV vaccination programmes with the quadrivalent or bivalent vaccines on infections by HPV 16 and 18 and HPV 31, 33, and 45 as a group, anogenital wart diagnoses, and CIN2+ among women.” They further found evidence of herd effects among boys and older women.

The investigators recommended that, “these results should be considered within the rapidly changing landscape of HPV vaccination, with several countries recently switching to two-dose schedules, gender neutral vaccination, and the nonavalent vaccine, and with research examining one-dose HPV vaccination, two-dose vaccination in older populations, and cervical cancer elimination strategies.” It will also be crucial, according to the investigators, to monitor the population-level effects of vaccination in low- and middle-income countries to understand the full effect of changes in vaccine strategies and to quantify these effects.

Reference

Drolet M, Bénard É, Pérez N, Brisson M, HPV Vaccination Impact Study Group. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis [published online June 26 2019]. Lancet. doi:10.1016/S0140-6736(19)30298-3