HPV test superior to Pap for long-term prediction of cancer risk
A single HPV test can predict a woman’s risk for cervical cancer for up to 18 years, or more than nine times as long as a traditional Pap smear, according to study results.
The data present additional support for the use of HPV testing in routine screening in women age 30 years or older, the researchers said.
“An HPV test provides greater reassurance against [grade-3 or higher cervical intraepithelial neoplasia] and cervical cancer than Pap testing and thus might be used as the screen to rule out disease in healthy women,” Philip E. Castle, PhD, and colleagues wrote. “Pap is useful as a secondary diagnostic test to identify HPV-positive women at immediate risk.”
Castle, executive director of the American Society for Clinical Pathology Institute in Washington, D.C., and colleagues conducted the study to evaluate the long-term benefits of clinical HPV testing for identification of cervical precancer and prediction of cancer risk.
The researchers collected cervicovaginal lavages from 19,512 women who participated in a prepaid health program at Kaiser Permanente in Portland, Ore. The researchers retrospectively tested the women for HPV. The women then underwent routine annual Pap testing for up to 18 years.
During the follow-up period, 396 cases of cervical intraepithelial neoplasia grade 2 or higher and 199 cases of CIN grade 3 or higher were diagnosed.
A positive Pap test was a strong indicator of a woman’s risk for cervical cancer within 2 years, whereas a positive HPV test predicted women who were at risk for cervical cancer for the duration of the study, the researchers wrote.
HPV-positive women were more likely to be diagnosed with CIN2+ (P<.001) and CIN3+ (P=.004) 10 to 18 years after enrollment compared with HPV-negative women, according to study results. Women with a positive Pap test were not more likely to be diagnosed with CIN2+ or CIN3+ than women with a negative Pap test.
The researchers said a one-time negative HPV test at baseline provided greater reassurance than a baseline normal Pap test against CIN2+ (cumulative incidence rate, 1.85% vs. 2.47%) and CIN3+ (cumulative incidence rate, 0.9% vs. 1.27%).
Among women whose one-time HPV and Pap tests were negative, cumulative incidence was 1.73% for CIN2+ and 0.83% for CIN3+, according to study results.
“We showed that clinical HPV DNA detection at one time point predicts cervical cancer risk for more than 15 years, identifying not only women who have prevalent CIN3+ but also those whose HPV infections will persist and develop into the disease,” Castle and colleagues wrote. “In contrast … cytologic abnormalities are a specific diagnostic marker for immediate, microscopic and visible disease, but it does not forecast clinically important disease between 1 or 2 years, hence the need to repeat it at much shorter intervals.”
In an accompanying editorial, Cornelia L. Trimble, MD, an associate professor of gynecology and obstetrics with Johns Hopkins Medicine, said the study results support risk-based screening that can be performed with tools already available as part of routine practice.
“The use of cervical HPV detection as a primary screen in appropriate cohorts — ie, older women in whom detectable HPV DNA is more likely than in younger women to reflect a persistent infection — could provide a way to triage the use of health care services,” Trimble wrote.
Disclosure: The research was supported by the NCI’s Intramural Research Program. The researchers report serving as consultants for or advisers to Merck, Qiagen and Roche, as well as having stock ownership in or receiving research funding from Qiagen.