Discussion
’, cancer, infections, infection, vaccine-specific oncogenic HPV infection
VIRUS, HPV INFECTION, PERSISTENT INFECTION, CANCER, INFECTIONS, INFECTION, CERVICAL CANCER
Three years after vaccine administration, the high efficacy of both single-dose bivalent or nonavalent HPV vaccine was sustained and durable against vaccine-specific oncogenic HPV infection. Protection against type-specific incident-persistent infection was ≥98% for bivalent and nonavalent vaccine protection against HPV 16/18 and >95% for nonavalent vaccine protection against HPV 16/18/31/33/45/52/58, which cause 70% and 90% of cervical cancer cases, respectively. This together with observed high reductions in the absolute cumulative incidence, the potential for public health impact in the context of disparities by HDI in cervical cancer incidence and mortalityTaken in context, these data contribute to a suite of studies that provide evidence for single-dose HPV VE. The Costa Rica vaccine trial (CVT)Of the 11.6 million cases of cervical cancer expected globally among girls born between 2005 and 2014, 75% of the burden will be concentrated in 25 countries largely in Africa and Asia, highlighting the need to focus prevention efforts among recently born girlsThe vaccines’ underlying immunological mechanism of action could explain the observed VE. The vaccines contain monomers that self-assemble into capsomers and VLPs, a highly immunogenic structure mimicking the ordered, repetitive virus epitope structure and allowing for crosslinking of B cell receptorsThe study has several strengths, including its randomized, double-blind controlled design, high retention rate, use of cervical HPV DNA as the outcome measure, determination of incident persistent HPV DNA, head-to-head comparison of the licensed bivalent and nonavalent HPV vaccines in protection against persistent infection with oncogenic HPV types, and duration of follow-up. Moreover, the trial successfully enrolled individuals exposed to HPV infection and retained them in all randomized groups, facilitating a rapid evaluation of single-dose efficacy. Compared to the 18-month analysis, the final analysis VE estimates are stable through 36 months, with higher point-estimates and tighter confidence intervals, as additional follow-up time was accrued beyond the 6–12-month buffer period, during which infections that were prevalent at baseline but not detected at follow-up, and may contribute to a lower estimate of VEWe acknowledge that the study has limitations. First, the median duration of follow-up is 35 months and longer-term durability of single-dose VE in a randomized trial would strengthen the evidence as HPV exposure continues through adulthood. Observational data for single-dose HPV vaccination support efficacy over a decadeGlobally cervical cancer is a leading cause of morbidity and mortality among women in mid-life; it is the second most common cancer and the greatest contributor to cancer-related mortality among women in southern and East Africa carrying a high cost to women, their families and communitiesOver 36 months, single-dose HPV vaccination offered high protection, >95% VE in preventing incident, persistent HPV 16/18/31/33/45/52/58 infection, with the lower bound of the confidence interval at almost 90% (89%) indicating a high minimum level of efficacy. Single-dose HPV vaccination was safe with no vaccine-related SAEs. These data add to the growing suite of evidence to support single-dose HPV vaccination implementation.