Should HPV Tests Replace Cervical Smears?

New studies have shown that the 60-year-old cervical smear test, “the best screening tool ever introduced for any cancer,” has competition or, at least, a companion. Studies from Sweden and Canada found that a DNA test, the HPV test, is better at identifying cervical cancer and high grade (grades 2 and 3) cervical intraepithelial neoplasia (CIN), a lesion that can progress to cancer. (The higher the grade, the more likely the lesion will progress to cancer.) Published in the 18 October 2007 issue of the New England Journal of Medicine, these large studies add evidence about the value of screening for human papillomavirus (HPV) in women over age 30. Younger women were not studied because they have more cases of HPV infections that resolve on their own and do not develop into cancer.

The Swedish Study: Smear plus HPV Test versus Smear alone
The Swedish study examined whether using the cervical smear and a sensitive HPV test together provided better long-term protection against cervical cancer than using the cervical smear alone. They tested two groups of women in their 30s, each numbering more than 6,000. Women with a positive HPV test and a normal smear were tested again at least one year later. If the test was still positive they were offered the ‘gold standard’ test – vaginal examination and biopsy of the cervix. A similar number of biopsies were done in the group who had only smears. At the start of the study and again at subsequent screening the researchers measured the number of cases of high-grade cervical intraepithelial neoplasia (CIN) or cancer found in each group

The authors found that HPV testing helped earlier diagnosis. At the initial examination, 51 percent more cases of CIN or cervical cancer were found in the women who had both tests. Appropriate treatment was offered to all women who had either test positive. At subsequent examinations, women who had received both tests initially had 42 percent fewer cases of CIN or cervical cancer, indicating that the earlier screening had been more effective when both tests were used.

The authors suggested that using both tests together may allow the interval between tests to be longer. However, they pointed out that more grade 2 CIN cases were found than when using cervical smears alone. Since grade 2 CIN is less likely to progress to cancer than grade 3, screening with both tests may have led to unnecessary treatment of some women.

The Canadian Study: Smear plus HPV Test together
The Canadians studied whether testing for HPV viral DNA is a better way to screen for cervical cancer than looking for abnormal cells in a cervical smear.

The randomized trial included more than 10,000 women aged 30 to 69 from 30 clinics in Montreal and St. John’s, Canada. They were divided into two groups that received both tests, but in a different order. Those that had an abnormal smear or a positive HPV test underwent the ‘gold standard’ test – vaginal examination and biopsy of the cervix, as did a random sample of women with negative tests.

The researchers found that the order the tests were given did not affect the reults. The HPV test detected 94.6 percent of cases of high grade CIN, whereas the smear test they used found only 55.4 percent. False positive results (2.7%) were only slightly more common with the HPV test than the smear. False positives are a concern because they expose patients to additional risks, which can include unnecessary testing and invasive medical procedures, as well as more expense and worry.

A New Era
These studies build a strong case for HPV testing. With the availability of the HPV vaccine and the  HPV test, the Canadian researchers noted “we are in a new era of cervical cancer prevention.”

The HPV test is highly reproducible, automated and needs few personnel, but requires expensive investment in equipment. Cervical smears not only sometimes miss abnormal cells, but they require highly trained personnel and specialized equipment.

However, traditional cervical smears that were used in both of these studies are fast being replaced by liquid-based cytology (LBC). The specimen is not "smeared" but put into a liquid preservative. The cell suspension is then processed on to a glass slide, stained, and examined. In 2003 the National Institute for Clinical Excellence recommended that LBC should be used as the primary means of processing samples in the cervical screening programme in England and Wales because of its greater accuracy.

A large study comparing the HPV test with LBC is underway and should provide evidence that will help determine the proper role of the HPV test.