Hutchinson Center study suggests HPV 18 may be useful for predicting prognosis of invasive cervical cancer

A strain of human papillomavirus called HPV 18, which is found in up to 30 percent of women with cervical cancer, appears to be associated with a mortality rate that's nearly double that of other HPV-related cervical cancers, according to a Fred Hutchinson Cancer Research Center study.

Results of the research, published today in the Journal of Clinical Oncology, confirm several previous, smaller studies that suggest HPV 18 may be an excellent molecular tumor marker for predicting the prognosis of women diagnosed with early-stage cervical cancer.

The National Cancer Institute-funded project, led by Stephen Schwartz, Ph.D., and colleagues, is the largest, most comprehensive and first population-based study to assess the viability of HPV 18 as a prognostic tumor marker for invasive cervical carcinoma.

"I think that the study potentially has very important clinical implications, as well as implications for new basic research," said Schwartz, an associate member of the Hutchinson Center's Public Health Sciences Division. "What is needed now is a trial to see if measuring the presence of HPV 18 in the tumors of cervical-cancer patients makes a difference in clinical outcome in terms of using this information to make treatment or monitoring decisions."

In other words, women with poorer prognosis, whose cervical tumors harbor HPV 18, perhaps could be treated more aggressively in the first place and monitored more frequently after initial treatment.

The findings also could impact the development of HPV vaccines for both treatment and prevention. "We don't know yet if such vaccines work, but if they do, there could be a trend toward patients getting their tumors tested to determine what strain of HPV is present, and then vaccinating them against that particular strain," said Schwartz, also an associate professor of epidemiology at the University of Washington School of Public Health and Community Medicine.

Human papillomavirus, a sexually transmitted disease that is the primary cause of cervical cancer, is present in virtually all cases of invasive cervical cancer. It is estimated that more than 6 million women in the United States are infected with HPV, of which there are more than 100 types. While all types can cause the growth of abnormal cells, usually only the high-risk variety - about a dozen of which so far have been identified - have been linked to cancer.

Schwartz and colleagues followed 399 women in western Washington with invasive cervical cancer at various stages. The women came from King, Pierce and Snohomish counties and were treated at a variety of hospitals. The women were followed for more than four years on average.

While the majority of these women tested positive for HPV 16 - the most common HPV strain linked to cervical cancer, accounting for about half of all cases - about 20 percent of the women in the study had HPV 18-related tumors. Adjusting for age, cancer stage and histological type, the risk of dying from cervical cancer was increased two-fold for patients whose tumors contained HPV 18 DNA compared to those whose tumors contained HPV 16 DNA.

The molecular mechanisms that cause HPV 18 to be associated with poor prognosis are unknown; basic research is needed to identify this link so new therapies can be developed to counteract this fast-growing, aggressive form of cervical cancer. Understanding these yet-to-be identified mechanisms, which may also be present at lower levels in other types of cervical cancer, could reduce deaths among all women with invasive cervical cancer.

"Although a tumor marker such as HPV 18 can be clinically valuable even when we don't know everything about what it does physiologically, knowing the mechanisms should maximize our ability to design treatments to counteract the marker's effect," Schwartz said.

Editor's note: A copy of the paper "Human Papillomavirus and Prognosis of Invasive Cervical Cancer: A Population-Based Study" Vol. 19, No. 7, pp. 1906-1915, 2001 can be obtained by calling the journal at 703-299-1016.

The Fred Hutchinson Cancer Research Center is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Recognized internationally for its pioneering work in bone-marrow transplantation, the Center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science.

The Hutchinson Center is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest. For more information, visit the Center's Web site at http://www.fhcrc.org. Advancing Knowledge, Saving Lives