Epidemiologic Evidence and Human Papillomavirus Infection as a Necessary Cause of Cervical Cancer

As with other malignant neoplasms, epidemiologic and laboratory studies conducted during the past 20 years have shown cervical cancer to be a disease with multifactorial causes and long latency. Unlike most other cancers, however, in which multiple environmental, biologic, and lifestyle determinants contribute independently or jointly to carcinogenesis, cervical cancer has been shown to have a central causal agent, human papillomavirus (HPV) infection ( 1 - 3 ), whose contribution to the risk of the disease is much greater than that of any other recognized determinant ( 4 ). On the basis of recent evidence from an international collaborative study ( 5 ) of more than 1000 cervical cancer specimens that used a highly sensitive polymerase chain reaction (PCR) protocol, researchers found that the prevalence of HPV DNA in cervical tumors was 93%. This is a higher estimate than had been observed previously in studies that used less meticulous methods for sample collection, preservation, and testing reviewed in ( 4 ). Reanalysis of specimens that remained HPV negative revealed that HPV DNA could be detected in other portions of the same specimen or by use of PCR with different primers, thereby raising the prevalence to higher than 95% ( 5 ). Similar strategies have also been used to show the presence of HPV DNA in virtually all cases of cervical intraepithelial neoplasia (CIN) ( 6 ).