Meta-analysis in human papillomaviruses 16/18 bivalent vaccine against cervical precancer

Objective To evaluate human papillomaviruses (HPV) 16/18 bivalent vaccine protection against cervical infection and precancer associated with HPV 16/18,thus providing a reasonable suggestion for vaccination population. Methods Clinical trials and data were retrieved from search engine of Web of science,Endnote X9 online search,Cochran Central Register of Controlled Trials (CENTRAL) and www.clinicaltrials.gov using topic words or key words consisting of HPV 16/18,bivalent vaccine,cervical neoplasm,clinical trial.Meta-analysis was conducted using Review manager 5.3 to assess the efficacy of HPV 16/18 bivalent vaccine against HPV infection and cervical precancer.Relative risks and statistical bias were also analyzed. Results Ten randomized trials (more than 40 000 cases) reported in 19 articles from 2004 to 2017 were identified.When young HPV-negative women at enrollment were vaccinated with three doses of (ATP-naive) or at least one dose (total vaccinated cohort-naive,TVC-naive) HPV16/18 bivalent vaccine compared with control women,relative risks of cervical incident infection,6-month persistent infection (PI) and 12-month PI associated with HPV16/18 were reduced by 68%-78%,82%-94% and 84%-97%,respectively;relative risks to develop cervical atypical squamous cell of undetermined significance and above (ASC-US+),cervical intraepithelial neoplasia of grade 1 and above (CIN1+) and CIN2+ associated with HPV16/18 infection were reduced by 89%-94%,87%-91% and 87%-92%,respectively.As compared with control women,relative risks of TVC-naive to develop ASC-US+,CIN1+,CIN2+,CIN3+ and adenocarcinoma in situ (AIS) irrespective of infection with HPV types were reduced by 28%-29%,50%,64%-72%,86%-93% and 93%,respectively.When young women regardless of HPV and DNA status at enrollment were vaccinated with at least one dose (TVC-E) of HPV16/18 bivalent vaccine compared with control women,relative risks to develop ASC-US+,CIN1+,CIN2+,CIN3+ and AIS associated with HPV 16/18 infection were reduced by 57%,50%,45%,34% and 70%,respectively;relative risks to develop ASC-US+,CIN1+,CIN2+,CIN3+ and AIS irrespective of infection with HPV types were reduced by 57%,50%,45%,34% and 70%,respectively. Conclusion HPV 16/18 bivalent vaccine provides excellent protection against both cervical HPV incident and persistent infection,as well as cervical precancer in HPV-negative young women.Even in people with different risks of HPV exposure,HPV16/18 bivalent vaccine has certain effect on reducing relative risks of cervical precancer and even carcinoma in situ.