Coconspirator? Genital herpes linked to cervical cancer

Nathan Seppa

Nearly every woman who contracts cancer of the cervix is also infected with the human papillomavirus (HPV). However, many women with HPV don't get cervical cancer. Scientists are trying to figure out why some of these infections lead to the cancer. They now report that if a woman has genital herpes in addition to HPV, her risk of cervical cancer nearly doubles.

HPV is the most common sexually transmitted disease in the United States, infecting roughly 24 million people. The virus comes in more than 60 types, yet most HPV infections go unnoticed. Some types of HPV cause only genital warts, or papillomas, which are unrelated to herpes. Two other types, HPV 16 and 18, are linked to cervical cancer.

To probe any herpes-cancer connections, Jennifer S. Smith, an epidemiologist at the International Agency for Research on Cancer in Lyon, France, and her coworkers analyzed blood and cervical cells obtained from women with and without cervical cancer who visited hospitals in Brazil, Colombia, Peru, Spain, Morocco, Thailand, and the Philippines. They ranged in age from 18 to 84, averaging 49 years. Overall, of 1,263 women with cervical cancer, nearly all also had detectable HPV. Of 1,117 women who didn't have the cancer, only 15 percent were infected with HPV.

Smith's team then compared women who were of similar age and had HPV infections of the same type but who differed in whether they had cervical cancer. Of those with cervical cancer, 44 percent had genital herpes. Among the women without the cancer, less than 26 percent had herpes. So, women with cancer were about 70 percent more likely to have herpes than were the other women. The researchers report their findings in the Nov. 6 Journal of the National Cancer Institute.

Precancerous sores on the cervix are detectable by a pap smear. If caught early, these lesions can be removed. This often prevents aberrant cells from progressing into a full-blown cancer. Once cancer develops, however, it can penetrate deeper and become far more difficult to treat.

The virus that causes genital herpes can also produce a lesion on the cervix. Although scientists don't know whether there's interplay between the herpes virus and HPV, a herpes infection might rev up HPV growth or help HPV spread deeper into cervical tissue, Smith says. Some scientists have proposed a hit-and-run theory, in which herpes changes some genetic material in a cell and then moves on, leaving it susceptible to further damage from an HPV infection.

Nancy Kiviat, a pathologist at the University of Washington and Harborview Medical Center in Seattle, focuses on chronic inflammation, which has been linked to liver and stomach cancers. "There's a tremendous inflammatory response to herpes," Kiviat says. This may exacerbate the HPV-induced cell damage that leads to cancer.

Moreover, gonorrhea and chlamydia infections, both of which can induce inflammation of the cervix, seem to hike the chance of HPV infections progressing to cervical cancer. Further research into the biological mechanisms by which various infections conspire with HPV to abet cervical cancer may lead to novel approaches for preventing the malignancy, Kiviat says.



Smith, J.S., et al. 2002. Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer. Journal of the National Cancer Institute 94(Nov. 6):1604-1613. Abstract available at;94/21/1604.

Further Readings:

Galloway, D.A., and J.K. McDougall. 1983. The oncogenic potential of herpes simplex viruses: Evidence for a 'hit-and-run' mechanism. Nature 302:21-24.

Hawes, S.E., and N.B. Kiviat. 2002. Are genital infections and inflammation cofactors in the pathogenesis of invasive cervical cancer? Journal of the National Cancer Institute 94(Nov. 6):1592-1593.

Smith, J.S., et al. 2002. Evidence for Chlamydia trachomatis as a human papillomavirus cofactor in the etiology of invasive cervical cancer in Brazil and the Philippines. Journal of Infectious Diseases 185(Feb. 1):324-331. Abstract.

Thomas, D.B., et al. 2001. Human papillomaviruses and cervical cancer in Bangkok. II. Risk factors for in situ and invasive squamous cell cervical carcinomas. American Journal of Epidemiology 153:732-739.

Additional information can be found at

York, I.A., et al. 1994. A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell 77(May):525-535. Abstract available at


Nancy Kiviat
University of Washington
Harborview Medical Center
325 Ninth Avenue
Seattle, WA 98104

Jennifer S. Smith
Unit of Field and Intervention Studies
International Agency for Research on Cancer
150 Cours Albert Thomas
F-69372 Lyon

From Science NewsVol. 162, No. 19, Nov. 9, 2002, p. 292.