Causal attribution of HPV genotypes to invasive cervical cancer: systematic analysis of the literature

Understanding the proportion of invasive cervical cancer caused by different HPV genotypes can inform primary (vaccination) and secondary (screening) prevention efforts that target specific HPV genotypes. A systematic review of the literature was carried out to estimate the proportion of ICC caused by different HPV genotypes. The review identified 1174 studies with 111,902 cases of HPV-positive ICC and 2,755,734 cases of normal cervical cytology. HPV genotypes with a lower bound of the 95% CI of the OR greater than 1.0 were judged as causal to ICC. This was the case for 17 HPV genotypes, with ORs ranging from 48.3 (95% CI 45.7-50.9) for HPV16 to 1.4 (1.2-1.7) for HPV 51. The global population attributible fraction (AF) was highest for HPV16 (61.7%), followed by HPV18 (15.3%), HPV45 (4.8%), HPV33 (3.8%), HPV 58 (3.5%), HPV31 (2.8%), and HPV52 (2.8%). Remaining causal genotypes had a combined global AF of 5.3%. AFs for HPV16 and HPV18 combined were lowest in Africa (71.9%) and highest in central, western, en southern Asia (83.2%). HPV35 had a higher AF in Africa (3.6%) than other regions (0.6-1.6%). The authors conclude that these data can inform HPV genotype-specific vaccination and screening strategies to reduce the burden of ICC.