For Immediate Release: July 17, 2001
Reprinted from the May/June 2001 DMS Digest
Contact: DMS Communications (603) 650-1520
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Dartmouth Promotes Cervical Cancer Screening and Prevention

Hanover, NH -- For every four sexually active women in America, three have already been exposed to the sexually transmitted disease human papillomavirus (HPV).That means HPV affects 75 million American women, yet for many it is a silent infection without overt physical symptoms. Unfortunately, this virus assumes a multitude of shapes and sizes when it does become visible. There are over 150 different HPV types, with effects ranging from cervical cancer to hand and feet warts. HPV-associated cancers are found in the throat and mouth as well as the genital area. Despite these overwhelming statistics, HPV remains nearly anonymous among the general public.

Diane M. Harper, MD
Photo courtesy of Dartmouth College of Public Affairs Office

Dartmouth Medical School physician Diane Harper, MD, MPH wants to change that. Harper, associate professor of community and family medicine and of obstetrics and gynecology, and a former MIT engineer, and her research team are working on projects to raise both awareness and prevention of HPV. Their studies may prevent millions of women from contracting HPV-related diseases like cervical cancer.

As the first step of the Dartmouth program, Harper is developing an HPV vaccine, using at least two of the cancer causing HPV types. Collaborating with industrial scientists, her goal is to provide protection against any infection with those types of HPV, thus preventing cervical cancer.The vaccine has additional importance for young girls not yet sexually active and not yet exposed to HPV. Working with project coordinator Kazuyo Masuda, Harper hopes to enlist the participation of high school girls and college women for the vaccine study. According to Masuda," Women who participate in this study may contribute to the health care of women, and will receive financial incentives."Those interested in learning more about the HPV vaccine can call Kazuyo Masuda at 603/650-2807.

Screening is a second important element of the Dartmouth program. Since many women unknowingly carry HPV, Harper stresses the importance of making the HPV test more accessible to women. She is designing a self-administered test for patients to use at home, and then mail to their doctors for analysis, partnering with Walter Noll, MD, professor of pathology, in the laboratory detection of HPV from the self-sampled devices. "This method allows women who wouldn't otherwise be examined to receive the test. A lot of women are uncomfortable getting speculum exams and this eliminates much of the discomfort since it is self-administered," Harper states. She is also investigating a tampon as a combined self-Pap smear and HPV test since, "Women are comfortable using a tampon and it provides similar HPV data to the swabs."

Self-sampling is now possible due to an advancement in the traditional Pap smear: liquid cytology. In liquid cytology, murky agents such as blood and mucous can be removed, leaving the cells more lucid for evaluation and rendering better results with increased information.Already liquid cytology has replaced 40% of traditional Pap smears, and Harper predicts that percentage will double within the next five years.The liquid Pap smear can test for the high-risk types of HPV, eliminating the need for additional tests, and increasing chances of pre-screening for harmful cancers. Jorge Gonzalez, MD, assistant professor of pathology, has instituted the liquid cytology method for Pap smear collection at DHMC.

Early detection of precursor lesions is the third element of Dartmouth's cervical cancer prevention. Once a patient receives an abnormal Pap result, the next step is colposcopy to examine the cervix under illumined magnification using acetic acid. However, colposcopy results are only correct 75% of the time due to the wide variation and inaccuracy of interpreting the changes, according to Harper, who is among less than 100 international experts in colposcopy.Working with Brian Pogue of the Thayer School of Engineering and Mary-Ann Mycek of the Physics Department, as well as a medical technology company, Harper instead supports the use of clearer biomarkers such as optical pattern scans or spectral signatures that discriminate between diseased and normal tissue. Spectral imaging is noninvasive for the patient, and it provides digital measurements at every pixel of an image in order to pinpoint any abnormalities. Spectral scans, the forefront of non-invasive diagnostic techniques, use many measures, including fluorescent and white light backscatter, to provide images that indicate abnormal tissue. Dartmouth is one of three sites in the world developing these scans for cervical cancer and its precursors.

In exploring the connections between HPV and cervical cancer, Harper is analyzing the cost effectiveness of improved screening and examining how advances will affect the quality of life for a woman with an abnormal Pap smear.With Anna Tosteson, ScD, associate professor of community and family medicine, she has gathered data on how false positive Pap smears affect the quality of life. The decrease in quality of life due to a false positive Pap smear, which occurs in about one million women annually, is substantial, she says.

Nationally, Harper is a member of the Steering Committee for the National Cancer Institute's ASCUS/ LSIL Triage Study (ALTS) and chair of the study's Quality of Life and Cost Effectiveness Analysis. ASCUS and LSIL are acronyms for two mild abnormalities Pap tests detect. She is working with Carol Hill Sox, MA, research assistant professor of community and family medicine, to design a model in cost effectiveness analysis that can influence changes in medical care which ALTS reports. Recently ALTS published two landmark articles, one in the February Journal of the National Cancer Institute reporting the value of HPV triage after an ASCUS Pap smear; the second in the March 21 Journal of the American Medical Association, on the need for more reliable screening methods for cervical cancer.

So why is it helpful to know if a woman has HPV? "It is incredibly important. If you know you have HPV, then regular screening becomes much more important so that you can prevent cervical cancer. This early screening in many developed countries is what has driven down cancer rates," Harper says. Although cervical cancer has dropped significantly in developed countries, in undeveloped countries it remains the number one cancer among women.Worldwide, cervical cancer affects half a million women annually, and after breast cancer, is the second most prevalent malignancy in women.

Harper presented ways to address the diagnosis and reporting of Pap test results at the National Cancer Institute's Bethesda 2001 Workshop April 30-May 2. She is a member of the national panel, sponsored by the American Society for Colposcopy and Cervical Pathology and NCI, which will recommend new evidence-based guidelines for clinical practice this September. She sits on the board of cervical cancer advisors for the American Cancer Society to evaluate the newest technological advances in cervical cancer screening and revise the interval screening recommendations, which are expected this fall. In addition, she heads a CDC-sponsored Breast and Cervical Cancer Early Detection program. The service, run by Anna Disco, provides free mammograms and Pap smears to women of qualifying incomes.

Sara Connolly, Dartmouth College '01
DMS Communications intern

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