Human papillomavirus and cancer: the epidemiological evidence.

OBJECTIVE: Summary of the studies carried out by the IARC on HPV and cervical cancer is presented. RESULTS: the first one was the international prevalence survey of HPV types in invasive cervical cancer (ICC) conducted in up to 22 countries. Overall, 99.7% of 1000 cases with histologically confirmed ICC were also shown to be HPV DNA positive using the GP5+/GP6+ or E7 primers, indicating that HPV is a necessary cause of cervical cancer. The most prevalent HPV types were HPV 16 (53%), HPV 18 (15%), HPV 45 (9%), HPV 31 (6%) and HPV 33 (3%). HPV 16 was the most common type in all geographical regions, followed by HPV 18 that was particularly, common in South-East Asia. The second set of studies included case-control studies carried out in 13 countries. They included about 2000 cases and 2000 controls. Positivity, for any HPV DNA yielded a pooled odds ratio (OR) of 70. The association was equally strong for both squamous cell (OR=74) and adenocarcinoma (OR=50) and for HPV 16 and 18 as well as for the less common HPV types. Our results indicate that in addition to HPV 16 and 18, HPV 31, 33, 35, 45, 51, 52, 58 and 59 now can be considered as carcinogenic. The third group of studies is aimed to determine the HPV DNA prevalence in random, age-stratified (by 5 years, 15-19 to 65+) subsamples (1100 women) of the general population. Two age-peaks (<25 and >59 years), have been found in some countries (Costa-Rica, Mexico, Colombia) but not in all (Argentina). Whether the second peak is due to viral reactivation, variations in screening or represents a birth-cohort effect remains to be determined. The distribution of the most prevalent HPV types in the general population (HPV 16, 18, 45, 31, 58, 33, 35) resembles that for cervical cancer cases. CONCLUSIONS: our studies provide the most solid epidemiological evidence, to conclude that HPV is not only the central cause of cervical cancer worldwide but also a necessary cause.