April 9, 2009

Pap Smear or HPV Testing for Cervical Cancer?

Cervical cancer screening and follow-up might one day come to the rural US via a mobile van. Or at least one might imagine such a scenario after reading a study published in the April 2 issue of the New England Journal of Medicine (NEJM).

George Sawaya

Cervical cancer may be caused by any of more than a dozen particular strains of sexually transmitted human papillomavirus, or HPV. The NEJM study of more than 130,000 women found that one-time screening and follow up using a DNA test to detect HPV strains associated with cervical cancer resulted in fewer cervical cancer deaths in later years in comparison to other screening methods, including the familiar “Pap” smear used to detect abnormal cells. The study, funded by the Bill and Melinda Gates Foundation, took place in India and included women between the ages of 30 and 59. Cervical cancer is common in developing countries, such as India, where few women have access to routine screening in comparison to most women in the United States. The study aimed to see if low-cost, one-time screening and immediate follow-up had any long term benefit over no screening. The answer appears to be yes. Women screened for either HPV or abnormal cells had fewer cervical cancers in the following years, compared to unscreened women. However, cervical cancer deaths appeared to be significantly reduced only among women screened with the HPV test. According to the researchers who conducted the study, “The reduction in the incidence of advanced cancers and deaths associated with HPV testing probably reflects the higher sensitivity of HPV testing to detect lesions with a high potential for malignant transformation than that of cytologic testing….” George Sawaya, MD, a UCSF gynecologist and epidemiologist who studies the costs and benefits of screening strategies, finds that explanation intriguing, but wonders if the failure to demonstrate fewer cervical cancer deaths among women screened with Pap smears was due to less-experienced cytologists interpreting Pap smears in comparison to cytologists working in US clinical labs. For cytology, “The issues of training, reproducibility and having patients return multiple times are problematic in low-resource areas,” he says. “I think this study was important because it showed that in low-resource areas screening can have a substantial impact on cervical cancer. The effect on mortality observed with HPV testing along with the problems with implementing high-quality cytology programs in these settings may well make HPV testing the favored option,” he adds. So, are the results in any way applicable to the United States? Unlike India, the US does not have a high incidence of cervical cancer. There are roughly 4,000 deaths due to the disease each year, placing it far down on the list of killer cancers. Physicians cited in a New York Times story about the study suggested that use of HPV testing could justify doing away with Pap smears and lengthening the interval between screenings to five years or more. Indeed, there is a trend toward increased screening intervals for women who already have had an earlier, negative test result. In the past women often were advised to receive Pap smears every year. Now the American Cancer Society and the American College of Obstetricians and Gynecologists outline a screening strategy whereby women can have both a Pap smear and an HPV test at the same time, and if they test negative for both, they would be asked to return for screening only at three-year intervals. But according to Sawaya, although clinical studies indicate that DNA tests for HPV detection are very sensitive, meaning they rarely miss cervical disease, they also appear to be less specific, meaning they may yield a positive result when no disease is present. For a cancer that occurs so rarely within a population – as with cervical cancer among US women -- a high rate of false positives, associated with invasive follow-up, weighs heavily against the benefit of a test being more sensitive, especially among frequently screened woman. “We need to consider potential harms and costs as well as potential benefits,” Sawaya says. In the United States, the price of the two types of tests are roughly comparable, depending on the provider and geographic region, he notes. One DNA test for HPV described in the Gates-funded study, called careHPV, yields results in three hours, compared to two weeks or more required to obtain results with tests that detect abnormal cells. Sawaya suggests that it’s possible that women with little or no access to testing services might one day benefit from a mobile screening unit -- similar to the mobile mammography vans found in some locales. Such a service would be able to provide HPV screening and follow-up care for women with a positive screening test on the same day.

HPV Screening for Cervical Cancer in Rural India

New England Journal of Medicine, Volume 360:1385-1394
Rengaswamy Sankaranarayanan, M.D., Bhagwan M. Nene, M.D., F.R.C.P., Surendra S. Shastri, M.D., Kasturi Jayant, M.Sc., Richard Muwonge, Ph.D., Atul M. Budukh, Ph.D., Sanjay Hingmire, B.Sc., Sylla G. Malvi, M.Sc., Ph.D., Ranjit Thorat, B.Sc., Ashok Kothari, M.D., Roshan Chinoy, M.D., Rohini Kelkar, M.D., Shubhada Kane, M.D., Sangeetha Desai, M.D., Vijay R. Keskar, M.S., Raghevendra Rajeshwarkar, M.D., Nandkumar Panse, B.Com., and Ketayun A. Dinshaw, M.D., F.R.C.R.
abstract | full text

HPV Screening for Cervical Cancer in Rural India

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