Hutch News Stories

Telltale Tumor Marker

Study suggests HPV 18 may predict prognosis of invasive cervical cancer
Dr. Steve Schwartz and r. Margaret Madeleine
In Dr. Steve Schwartz' office at Met Park East, Schwartz and Dr. Margaret Madeleine examine data on cervical-cancer incidence in women infected with human papillomavirus. photo by Clay Eals

A strain of human papillomavirus called HPV 18, found in up to 30 percent of women with cervical cancer, appears associated with a mortality rate nearly double that of other HPV-related cervical cancers.

Results of the Hutch research, published in the March 29 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 Dr. Stephen Schwartz 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.

Important implications

"The study potentially has important clinical and basic-research implications," Schwartz said. "What is needed 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 and monitored more frequently after initial treatment.

The findings also could impact development of HPV vaccines for 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. More than 6 million U.S. women 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 were from King, Pierce and Snohomish counties and treated at hospitals for an average of more than four years.

Two-fold risk

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 had HPV 18-related tumors. Adjusting for age, cancer stage and histological type, the risk of dying from cervical cancer doubled for those whose tumors contained HPV 18 DNA instead of HPV 16 DNA.

The molecular mechanisms that associate HPV 18 with poor prognosis are unknown; basic research is needed so new therapies can counteract this fast-growing, aggressive form of cervical cancer. Understanding these 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.

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