The Pap test has been enormously successful at reducing cervical cancer deaths, but it can miss early signs of malignancy, allowing undetected cases to become invasive.

New research from a large-scale screening program shows that testing the DNA from the human papillomavirus (HPV) in a sample of cervix cells appears to be better at detecting threatening precancerous cells than the standard visual inspection of epithelial and other cells for a Pap. The result confirms previous findings from smaller studies.

Some forms of HPV can cause cervical cancer, which is responsible for about 4,070 deaths in the U.S. each year. And although many U.S., Canadian, Australian and European girls and young women have been vaccinated against the sexually transmitted virus in the past few years since the vaccine became available, it continues to spread among unprotected males and females—and other types not included in the vaccine can still infect inoculated individuals.

The new study, published online April 27 in BMJ, enlisted 58,076 Finnish women aged 30 to 60, who were randomly assigned to either a conventional cytology-based Pap smear or one that relied primarily on an HPV DNA sample for their cervical cancer screening. (Women who tested positive for severe precancerous lesions in the HPV test were recommended to have a follow-up cytology triage.) After an average follow-up time of 3.3 years, there were 59 confirmed cases of severe cervical intraepithelial neoplasia or adenocarcinoma (CIN III+) in the HPV testing group and 33 cases in the standard group. Fifty-seven of the 59 cases in the HPV-tested group had tested positive for CIN III+, whereas 26 of the 33 cases in the traditional Pap test group had previously tested positive.

Although the numbers of confirmed positives were small overall, the researchers, led by Ahti Anttila research director of the mass screening registry of the Finnish Cancer Registry in Helsinki, concluded that including this test in larger cervical cancer screening programs could help reduce the number of invasive cases, of which there are more than 11,000 diagnosed each year in the U.S.

Due to the test's sensitivity, however, HPV-based tests might often turn up evidence of less threatening cells belonging to CIN I and CIN II categories "at an earlier age, thus potentially affecting quality of life," the authors noted. But for women 35 or older, whose bodies are less likely to fight off a precancerous infection, the improved detection could be "important for prevention of cervical cancer," the researchers concluded in their study.

More false positives could be a big drawback to HPV DNA tests, which return about 6 percent false positives, according to a 2007 study—especially when Pap tests, which have a false positive rate of about 3 percent already produce about 4 million "abnormal" readings each year. Based in part on these poor Pap test stats, in November 2009 the American College of Obstetricians and Gynecologists recommended that most women need only get screened after the age of 21 and every two to three years thereafter to reduce the prevalence of worrisome—and pricey—false positives and unnecessary treatment. Although an HPV DNA test is approved for use with traditional Pap tests in the U.S. for women over the age of 30, it remains to be seen whether it will become a primary tool in the fight against cervical cancer.

Image of normal cells (left) and HPV-infected cells (right) courtesy of Wikimedia Commons