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Beyond Human Papillomavirus: The Cervix, Exogenous Secondary Factors, and the Development of Cervical Precancer and Cancer

Castle, Philip E. PhD

Journal of Lower Genital Tract Disease: July 2004 - Volume 8 - Issue 3 - p 224-230
Basic Science

Human papillomavirus (HPV) is the necessary but probably not sufficient cause of cervical precancer and cancer. Secondary exogenous and endogenous factors, HPV cofactors, may contribute to the probability of a cancer-associated (oncogenic) HPV infection progressing to cervical precancer and cancer. For these cofactors to influence the natural history of HPV infection, they must act on cervical tissue to promote viral persistence, progression to precancer or cancer given viral persistence, or both. The aim of this review was to examine briefly the impact these factors may have on carcinogenesis of the cervix. Specifically, the roles of the cervical transformation zone, cervical immunity, inflammation and coinfection, and exposure to the main HPV cofactors (smoking, oral contraceptive use, and multiparity) are discussed.

Exposure to secondary factors with a concurrent HPV infection may increase the risk of cervical precancer and cancer.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD

Reprint requests to: Philip E. Castle, PhD, MPH, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Room 7074, EPS MSC 7234, Bethesda, MD 20892–7234. E-mail:

©2004The American Society for Colposcopy and Cervical Pathology