Research in context
Evidence before this study
The quadrivalent human papillomavirus (qHPV; 6, 11, 16, and 18) and bivalent HPV (16 and 18) prophylactic vaccines were first licensed in 2006 and 2007, respectively. We searched PubMed with no language restrictions for articles published between Jan 1, 2000, and Sept 1, 2016, with the terms “HPV type detection” AND “cervical cancer” AND “worldwide”, and found several epidemiology studies showing that the HPV types most commonly associated with cervical cancer are HPV 16 and HPV 18, and the next five most common types are HPV 31, 33, 45, 52, and 58. Another PubMed search between Jan 1, 2007, and Sept 1, 2016 based on the terms “HPV vaccine” AND “cross-protection” AND (“clinical trial” OR “epidemiology”) found that partial cross-protection against oncogenic HPV types other than HPV 16 and HPV 18 has been reported for both licensed vaccines in clinical trials and real-world public health programmes, although its extent, duration, and public health significance remain uncertain. Finally, we searched PubMed with the search terms “HPV vaccine” AND “clinical trial” to identify studies published between Jan 1, 2007, and Sept 1, 2016, that assessed broader spectrum prophylactic HPV vaccines other than the nine-valent (HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine (9vHPV). We found one phase 2 study of two tetravalent vaccine candidates targeting HPV 16, 18, 31, and 45 and HPV 16, 18, 33, and 58, respectively; however, vaccine development was unsuccessful because of immune interference.
Added value of this study
This is the first phase 3 efficacy clinical trial of a 9vHPV vaccine. Primary analyses previously showed efficacy against infection and disease due to HPV 31, 33, 45, 52, and 58 and non-inferior HPV 6, 11, 16, and 18 antibody responses at 1 month after vaccination compared with the qHPV vaccine. Here we document persistence of efficacy against infection and disease for up to 6 years, a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18 over the entire study, and substantial reductions in abnormal cervical cytology and related clinical procedures. Taken together, these results suggest substantial protection against disease caused by HPV 31, 33, 45, 52, and 58 that augments protection against HPV 6, 11, 16, and 18 with the qHPV vaccine.
Implications of all the available evidence
The 9vHPV vaccine is licensed in more than 60 countries for the prevention of HPV-related anogenital cancers and pre-cancers, and genital warts. The results of this study support comprehensive vaccination programmes and inform public health decisions related to implementation. Additionally, these findings inform further refinement of cervical cancer screening algorithms for vaccinated populations. Previously developed HPV vaccines cover oncogenic HPV 16 and 18, which cause approximately 70% of cervical cancer cases worldwide; the 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide. It could also prevent nearly 90% of HPV-related vulvar and vaginal cancers, 70–85% of high-grade cervical disease in females, as well as 90% of anal cancers and of genital warts in both males and females.