Is one dose of human papillomavirus vaccine as effective as three?: A national cohort analysis
Brotherton, J. M., Budd, A., Rompotis, C., Bartlett, N., Malloy, M. J., Andersen, R. L., Coulter, K. A., Couvee, P. W., Steel, N., Ward, G. H., & Saville, M. (2019). Is one dose of human papillomavirus vaccine as effective as three?: A national cohort analysis. Papillomavirus Research, 8.
Aim: Prophylactic human papillomavirus (HPV) vaccines are highly eﬀective at preventing pre–cancerous cervical lesions when given in a three–dose schedule. Some post–hoc trial data suggest that one dose prevents HPV infection. If one dose could prevent pre–cancerous cervical lesions, then global cervical cancer prevention would be greatly facilitated. We assessed the eﬀectiveness of quadrivalent HPV vaccine by number of doses against cervical intraepithelial neoplasia (CIN) 2 or 3/adenocarcinoma–in–situ (AIS)/cancer in Australia up to seven years post vaccination.
Methods: We linked registry data from all 8 jurisdictional cervical screening registers, with the national HPV vaccination register, death index and cancer registers for all Australian women aged 15 or under when eligible for vaccine who screened between April 2007 (when vaccination commenced) and 31 December 2014. We performed Cox proportional hazard regression, adjusted a priori for age, socioeconomic status, and area of residence, to estimate hazard ratios of histologically conﬁrmed CIN2/CIN3/AIS/cancer.
Results: We included 250,648 women: 48,845 (19·5%) unvaccinated, 174,995 (69·8%) had received three doses, 18,190 (7·3%) two doses and 8,618 (3·4%) one dose. The adjusted hazard ratio was signiﬁcantly lower for all dose groups compared to unvaccinated women (1 dose 0·65 (95%CI 0·52–0·81), 2 doses 0·61 (0·52–0·72) and 3 doses 0·59 (0·54–0·65).) With adjustment for age at vaccination amongst the vaccinated group, the adjusted hazard ratios for one dose and two dose recipients were comparable to three dose recipients (one dose 1.01 (95%CI 0.81–1.26), two doses 1.00 (0.85–1.17).) Multiple sensitivity analyses, including use of diﬀerent dose assignment methods, produced consistent ﬁndings. Comparison with a historical cohort of age matched women showed that the result was not due to herd protection alone.
Conclusions: One dose had comparable eﬀectiveness as two or three doses in preventing high–grade disease in a high coverage setting. These ﬁndings support the hypothesis that one dose vaccination may be a viable strategy when working towards the global elimination of cervical cancer.
human papillomavirus, vaccination, effectiveness, cervical intraepithelial neoplasia, Australia