Cervical Cancer Risks After Negative HPV Test Lower at 3 Years Than After Negative Pap Result

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Three-year risks for cervical cancer and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) were lower following a negative test for human papillomavirus (HPV) than following a negative Pap test, according to a large study comparing three cervical cancer screening strategies, HPV or Pap testing every 3 years, or cotesting every 5 years). The study also found that 3-year risks following a negative result with HPV testing alone were lower than the 5-year risks following a negative result with cotesting.

Julia C. Gage, PhD, MPH, of the National Cancer Institute, Bethesda, Maryland, and colleagues analyzed data from the Kaiser Permanente Northern California, a large integrated health delivery system with a large well-established cervical cancer screening program that screened women at approximately 3-year intervals, with a mean follow-up time of 4.36 years. “With newly available data through 2012, we were able to estimate risks among more than 1 million women,” the investigators noted.

For each testing strategy, the investigators used logistic regression and Weibull survival models to estimate the cumulative risk of cervical cancer after a negative test result. The 3-year risk for cervical following a negative HPV result was lower than the 3-year risk following a negative Pap test (0.011% vs 0.020%, P < .0001) and lower than the 5-year risk following an HPV-negative/Pap-negative cotest (0.011% vs 0.014%, P = .21). The 3-year risk for CIN3+ was also lower following a negative HPV result than a negative Pap test (0.069% vs 0.19%, P < .0001) and lower than the 5-year risk following an HPV-negative/Pap-negative cotest (0.069% vs 0.11%, P < .0001).

Optimal Screening Interval for HPV Testing

"This analysis focused on 3-year risks after a negative HPV test, because a 3-year screening interval is under consideration for initial introduction of primary HPV testing in the U.S,” the authors wrote. “Yet, the optimal screening interval for primary HPV testing has not yet been established and might exceed 3 years, as has been advocated in Europe. European screening trialists suggest that HPV screening can be safely implemented with at least a 5-year interval, and countries are implementing extended screening intervals.”

The investigators concluded that “primary HPV testing every 3 years might provide as much, if not more, reassurance against precancer and cancer, compared to primary Pap testing every 3 years and cotesting every 5 years.” The researchers also cautioned that “further consideration is required to define the optimal screening interval within the context of patient benefits (ie, cancer prevention) and harms (eg, increased screening visits, colposcopy and treatment). Analyses should also incorporate risks and resource utilization after multiple screening rounds across screening strategies.”

In an accompanying editorial, Jane J. Kim, PhD, of the Harvard School of Public Health, Boston, noted that the HPV test approved for primary screening specifically assays the two highest-risk HPV types (16 and 18) that account for 70% of cervical cancers but pools the assay for the other 12 HPV strains.

“There is not yet enough evidence to indicate that HPV primary testing is the optimal approach to cervical cancer screening,” Dr. Kim wrote. “But increasingly, we are seeing robust evidence—in clinical trials and now in real-world practice—that gives confidence in the safety and effectiveness of primary HPV testing, at least relative to Pap testing as is currently recommended in the United States.” ■

Gage JC, et al: J Natl Cancer Inst 106(8):dju153, 2014.

Kim JJ: J Natl Cancer Inst 106(8):dju213, 2014.