Smoking and Very High Risk Viruses Pose Greater Danger for Cervical Cancer Patients

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Cause of Cervical Cancer

Cervical cancer patients infected with either of two strains of human papillomavirus (HPV) were twice as likely to die of their disease as patients with other common strains of HPV, making these strains very high-risk forms of the virus, according to a study at Washington University School of Medicine in St. Louis. In addition, members of this group who smoked increased their risk of death even further.

Nearly all cervical cancers are associated with HPV infection of the cervix, which is now recognized as the major cause of cervical cancer. (Note, however, that only a small fraction of women with HPV infection of the cervix actually go on to develop cervical cancer.)

"Cervical cancer is the second most common cancer in women worldwide," says Jason D. Wright, M.D., a Washington University gynecological oncologist at Barnes-Jewish Hospital and associated with the Siteman Cancer Center. "It's clear that HPV plays a role, but there are differences among viral strains that influence the progression of the disease."

More than 80 strains of HPV are known to exist, and scientists divide the viruses into low- and high-risk groups. The low-risk viruses can lead to noninvasive growths such as genital warts, while high-risk viruses are implicated more frequently in preinvasive and invasive cervical cancers.

HPV strains 18 and 45 are closely related, high-risk viruses. HPV 18 recently has been linked to a greater likelihood of disease recurrence in cervical-cancer patients, but it's relation to survival has remained uncertain.

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Of the 255 cervical-cancer patients compared in this study, recently published in Gynecologic Oncology, 65 were infected with either HPV 18 or 45. The rest had a variety of other high-risk HPV strains.

Five years after initial treatment, 29 percent of cervical-cancer patients with HPV 18 or 45 had suffered a recurrence of their tumors, and 24 percent had died of cervical cancer. In contrast, of those patients with the other HPV strains, only 19 percent had a recurrence, while 15 percent had died.

The researchers calculated a hazard ratio of 2.08 for patients with HPV 18 or 45, indicating that for a similar tumor stage and lymph node involvement, these patients were about twice as likely to die from their disease as patients infected with other high-risk strains of the virus. These two strains are therefore among the most dangerous of the high-risk strains of HPV.

"HPV 18 and 45 are associated with more aggressive cancer that spreads earlier," Wright says. "Other studies suggest that HPV 18 transforms more normal cells into cancerous cells than HPV 16, another high-risk virus strain."

Tobacco smoke contains at least 40 known human carcinogens, and several smoke constituents have been found in cervical secretions of women smokers. When the hazard ratio was calculated for patients with HPV 18 or 45 who also smoked, the ratio was 4.06, a second doubling of the risk of death.

The researchers are continuing to study HPV 18's association with cervical cancer. They plan future studies to investigate the molecular causes for the increase in aggressive cancers with this strain of the virus.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare. - Sept. 8, 2005

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