Prevention of human papillomavirus-associated cancers

The oncogenic, anogenital types of human papillomavirus (HPV) are established as causing about 4.8% of all human cancers worldwide, particularly cervical, anal, vulvar, vaginal, penile, and oropharyngeal cancers. Quantitative knowledge of the HPV type-specific risks for these cancers, as well as for the different cervical cancer precursors (cervical intraepithelial neoplasias, CINs), is useful for estimating the effect of elimination of specific HPV types and clinical benefits of screening for specific HPV types. The present review summarizes both the worldwide presence of specific HPV types in cervical cancer precursors and in invasive cervical cancers, and also the long-term follow-up data from a large randomized clinical trial of HPV-based cervical cancer screening. All 12 HPV types classified as class I (established) carcinogens (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) were more common in cervical cancers than among women without cervical lesions. A few rare HPV types also were more common in cervical cancers (eg, HPV26, 67, 68, 69, 73, 82). The follow-up studies found increased long-term risks particularly for HPV types 16, 18, 31, and 33, which had 14-year cumulative incidences for CIN3+above 28%, while HPV35, 45, 52, and 58 had 14-year risks between 14%-18% and HPV39, 51, 56, 59, 66, and 68 had risks<10%. HPV16 contributed to the greatest proportion of CIN2+(first-round population attributable proportion [PAR] 36%), followed by types 31, 52, 45, and 58 (7%-11%). HPV16, 18, 31, 33, 45, 52, and 58 together contributed 73.9% of CIN2+lesions and all high-risk types contributed 86.9%.In summary, the different oncogenic HPV types have substantial differences in their oncogenic potential. These differences are relevant for the design and evaluation of cervical screening tests and programs, as well as for studying the effect of vaccination programs using different HPV vaccines.