Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Viruses in oncogenesis: The role of human papilloma viruses

EL Franco PhD

Departments of Oncology and Epidemiology, McGill University, Montreal, Canada,

The epithelial lining of the anogenital tract is the target for infection by a group of mucosotropic viruses, the human papilloma viruses (HPV). Subclinical and clinical genital warts, also known as condylomata acuminata, and probably most malignant lesions of the anogenital tract are caused by specific HPV types. HPVs are DNA viruses with an approximately 8000 base-pair genome size. There are more than 100 HPV types defined on the basis of DNA homology, of which more than 40 infect the anogenital tract. Clinical and latent HPV infections are the most common sexually-transmitted diseases today, with a prevalence of 10%-40% among women of reproductive age. Recent number of sexual partners is the most important risk factor for HPV infection. Another important determinant is age, which is negatively correlated with risk. Other risk factors seem to be less consistent or are prone to geographical specificity. Acquisition and clearance of HPV infection has been investigated in cohort studies with repeated measurements using HPV DNA hybridization techniques. Incident HPV infection occurs after one year in about 20% of women who test negative at enrollment in natural history cohorts. Of those positive at entry only one third retain the original HPV type after one year of follow-up. Risk of cervical cancer is strongly linked to persistent infection. Persistent HPV detection is associated with an oncogenic HPV type and a high viral load. The International Agency for Research on Cancer (IARC) has concluded that there is compelling evidence, both from the biologic and from the epidemiologic standpoints, to consider HPV infection as cause of cervical cancer. The IARC has evaluated HPV infection by types 16 and 18 as carcinogenic to humans (group 1). Infection by some other types, such as HPVs 31 and 33, is classified as probably carcinogenic (group 2A) and, except for HPVs 6 and 11, types other than 16, 18, 31, and 33 are considered possibly carcinogenic to humans (group 2B). For diagnostic triage and screening purposes, HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 are considered to be of high oncogenic risk. The relative risks of cervical cancer for HPV as exposure ascertained in case-control and cohort studies are in the 20 to 100+ range, which places HPV infection as the strongest risk factor for cervical cancer with a magnitude of association that is greater than that for the relation between smoking and lung cancer and is comparable only to that of the association between chronic hepatitis B infection and liver cancer, causal relations in cancer that are no longer challenged. Meticulous testing by polymerase chain reaction of cervical carcinoma specimens shows that virtually all cases contain HPV DNA, which would suggest that HPV infection may be a necessary cause of cervical neoplasia. If confirmed, this would be the first instance in which a necessary cause would have been demonstrated in cancer epidemiology - a realization that has obvious implications for primary and secondary prevention of cervical cancer.

KEY WORDS: human papilloma viruses.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on environment & lifestyle.