Herpes simplex virus-2 may increase risk of cervical cancer

November 05, 2002

The herpes simplex virus-2 (HSV-2) appears to be an accomplice to the human papillomavirus (HPV) in causing some cases of cervical cancer, according to a study in the November 6 issue of the Journal of the National Cancer Institute. HPV infection is the main cause of cervical cancer. However, it has been suggested that other factors act in conjunction with HPV to further increase this risk. These factors include smoking, number of live births, duration of oral contraceptive use, and sexually transmitted infections such as HSV.

Using case-control study data from seven countries with different incidences of cervical cancer, Jennifer S. Smith, Ph.D., and her colleagues from the International Agency for Research on Cancer (IARC) Multicentric Cervical Cancer Study Group examined blood and cervical specimens from 1,263 women with cervical cancer and 1,117 women without cervical cancer for the presence of HPV DNA, and for HSV-2 antibodies (a marker for past HSV-2 infection) and other potential cofactors for cervical cancer.

The authors detected HSV-2 antibodies in the blood of 44.4% of women with squamous-cell carcinoma and in 43.8% of women with adenocarcinoma/adenosquamous-cell carcinoma (types of invasive cervical cancer), but HSV-2 antibodies were found in only 25.6% of women without cervical cancer. The authors found HPV DNA in the cervical tissue specimens of 94.8% of women with squamous-cell carcinoma and 90.5% of women with adeno- or adenosquamous carcinoma, but only 14.7% in cervical specimens of women who did not have cervical cancer. Of the women who tested positive for HPV DNA, past infection with HSV-2 was associated with a more than twofold increase in risk of squamous-cell carcinoma, and a more than threefold increase in risk for a smaller number of adenocarcinoma/adenosquamous carcinoma cases.

The authors conclude that HSV-2 infection may act in conjunction with HPV infection to increase the risk of invasive cervical cancer. They note, however, that "although HSV-2 infection may act in conjunction with HPV infection to increase the risk of invasive cervical cancer, the effect of HSV-2 infection on invasive cervical cancer risk is modest compared with the strong effect of HPV infection on invasive cervical cancer risk."

In an accompanying editorial, Stephen E. Hawes, Ph.D., and Nancy B. Kiviat, M.D., of the University of Washington School of Public Health and Community Medicine in Seattle, say that the specific role of HSV-2 or other infectious agents in the development of cervical cancer remains unclear. They postulate that HSV-2 and other infectious agents may trigger an inflammatory response, which generates DNA-damaging free radicals, which are thought to play important roles in the initiation and the progression of cancers.

"Further studies of the natural history of HPV infection in relation to infection with other cervical pathogens may provide insights into the mechanisms by which ulcerative sexually transmitted infections and inflammation contribute to the development of the malignant phenotype and may suggest novel approaches to the prevention of cervical neoplasia," they say.
Contact: Jennifer Smith, International Agency for Research on Cancer, cell phone: 33-616-473-460 (Friday 10/31 until 11:00 a.m. ET; Monday 11/4 from 9:00 a.m. to 10:00 a.m., and after 12:30 p.m. ET), smith@iarc.fr
Editorial: Walter Neary, University of Washington, 206-685-3841; fax: 206-685-3333, wneary@u.washington.edu

Smith J, Herrero R, Bosetti C, Muòoz N, Bosch F, Eluf-Neto J, et al. Herpes simplex-virus-2 as a human papillomavitus cofactor in the etiology of invasive cervical cancer. J Natl Cancer Inst 2002;94:1604-13.

Editorial: Hawes S, Kiviat N. Are genital infections and inflammatory cofoactors in the pathogenesis of invasive cervical cancer? J Natl Cancer Inst 2002;94:1592-3.

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.

Journal of the National Cancer Institute

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