Positive HPV Test Predicts Cervical Precancer for 18 Years

Testing for human papillomavirus (HPV) can predict which women will develop cervical precancers for 10 to 18 years after the test is conducted.

A large study examined the long-term benefits of HPV DNA testing alone, cytology (Pap testing), and combinations of the two, to predict cervical precancerous disease and invasive cervical cancer risk.

Results of the study showed that while both a positive HPV test and an abnormal Pap test predicted which women would develop precancers within two years of testing, the positive HPV test continued to predict which women were at risk for the entire 18-year follow-up of the study. An initial negative HPV test, on the other hand, provided greater reassurance against cervical precancer and cancer over 18 years than a one-time normal Pap test. The results of the study were published in the July 30, 2012 online issue of the Journal of Clinical Oncology.

The study participants were 20,000 women receiving routine Pap screening at Kaiser Permanente (Portland, OR, USA). The women underwent baseline Pap tests as part of routine care, and high-risk HPV testing for research purposes, and were followed up by conventional Pap testing for up to 18 years. The cumulative incidence was calculated for two different outcomes, CIN2 or the more severe (CIN2+), and CIN3 or more severe diagnoses (CIN3+). CIN2 and CIN3 are precancerous conditions in which abnormal epithelial cells have replaced normal epithelial cells in the cervix. These abnormal cells are not malignant but may eventually lead to cancer.

A US Food and Drug Administration (FDA; Silver Spring, MD, USA)-approved molecular test, which screens for a pool of 13 high-risk HPV types, was used for baseline HPV testing. Those women who tested positive on the pooled test were also tested for HPV16 and HPV18 separately, using a prototype clinical assay. These two high-risk types are known to account for approximately 55% and 15% of all HPV strains respectively.

Among study participants older than 30 years, 8.7 percent tested HPV-positive and 4.3 had an abnormal Pap test result at initial testing. More cases of CIN3 and cervical cancer occurred after a baseline HPV-positive result versus abnormal Pap over the 18-year period (112 versus 65). HPV-positive women were more likely to have precancer at 10 to 18 years than HPV-negative women, regardless of the result of their initial Pap test. Thus, positive HPV test results were better at forecasting long-term cervical cancer risk than abnormal Pap results.

Over the 18-year follow-up, the incidence of CIN3 and cervical cancer was lower after a one-time negative HPV test than after one normal Pap test (0.9% vs. 1.27%), suggesting that HPV testing is a stronger predictor of not developing cervical precancer years later. Finally, the study showed that, among women older than 30 years who had negative HPV and normal Pap tests, increasing the screening interval from 3 years to 5 years did not substantially increase the CIN3 and cervical cancer risk (0.08% vs. 0.16%).

The study also found that, over an 18-year period, HPV16- and HPV-18 positive women with normal Pap results were at elevated risk of developing CIN2, CIN3, and cervical cancer compared with other HPV-positive women with normal Pap.

“While we knew that testing for high-risk HPV can predict cervical cancer risk for a few years, it’s remarkable that this predictive effect lasts for almost two decades,” said senior study author Philip E. Castle, PhD, MPH, of the American Society for Clinical Pathology (ASCP). “Our findings strongly reinforce the value of HPV testing as a routine part of care, in line with recent guidelines.”

Dr. Castle emphasized that the biggest obstacle to reducing cervical cancer deaths in the US remains limited access to screening for some women. “Half of all cervical cancers in the U.S. are diagnosed in medically underserved women. They have incidence and mortality rates that are consistent with second and third world countries. We have to find ways to reach those women with any screening modality,” he said.

Related Links:
Kaiser Permanente
US Food and Drug Administration
American Society for Clinical Pathology