A negative human papillomavirus (HPV) test may provide better reassurance against cervical cancer than a Pap test alone and similar reassurance compared with the use of the two tests combined (cotesting), according to a recent retrospective study.1

Current guidelines recommend that women 30 to 65 years undergo cotesting for primary cervical cancer screening every 5 years, or, alternatively, primary Pap testing with HPV testing for clarification of equivocal results every 3 years. Primary HPV testing every 3 or more years is currently being considered by the U.S. Food and Drug Administration and professional societies as a recommended cervical cancer screening strategy.

To compare the effectiveness of the various strategies, researchers at the National Cancer Institute examined data from the Kaiser Permanente Northern California health care delivery system, where women older than 30 years have been screened with cotesting since 2003. The data set included 1,037,021 women who were 30 to 64 years and screened at approximately 3-year intervals between 2003 and 2012. Mean follow-up was 4.36 years.

Continue Reading

RELATED: New HPV Test Highly Predictive of Cervical Cancer

The researchers estimated the reassurance against future risk of cancer and precancerous conditions for primary HPV testing alone, primary Pap testing alone, and cotesting.

They found that the 3-year risk after a negative HPV test was lower than the 3-year risk after a negative Pap test for cervical intraepithelial neoplasia grade 3 or higher (CIN3+) (0.069% vs. 0.19%, P<0.0001) and for cervical cancer (0.011% vs. 0.020%, P<0.0001).

Moreover, the 3-year risk after a negative HPV test was lower than the 5-year risk after negative cotesting for CIN3+ (0.069% vs. 0.11%, P<0.0001) and for cervical cancer (0.011% vs. 0.014%, P<0.0001).

Compared with Pap testing, HPV testing missed fewer cases of cervical adenocarcinoma (47.4% vs. 11.4%, P<0.0001) and adenocarcinoma in situ (51.1% vs. 18.7%, P<0.0001).

From these data, the authors concluded that it is primarily the HPV component of cotesting that provides its negative predictive value, and that primary HPV testing “merits consideration as another alternative for cervical screening”.

They note, however, that the optimal screening interval for HPV testing has not been determined and might exceed 3 years.

A key issue is how a change in screening strategies would affect the management of women with positive results. A projection of management outcomes associated with the various strategies determined that testing HPV alone would result in a 15% reduction in immediate referrals for colposcopy. However, approximately one-half of women in the cohort with HPV-positive, Pap-negative results still had positive results when they were retested at 1 year, which would lead to an overall increase in referrals for colposcopy.

RELATED: HPV Vaccine Doesn’t Increase VTE Risk

In an accompanying editorial, Jane J. Kim, PhD, of the Harvard School of Public Health, wrote that “having multiple effective options for primary cervical cancer screening is both a blessing and a curse.”2 She pointed out that it is so far uncertain whether HPV primary testing will simplify or complicate cervical cancer screening and management algorithms, and that greater complexity of management choices inevitably leads to poorer guideline adherence.

“As primary HPV testing is rolled out in clinical practice,” Dr. Kim stated, “studying outcomes, both harms and benefits, across different healthcare settings and diverse populations will be imperative for guiding decision-making.”


  1. Gage JC, Schiffman M, Katki HA, et al. Reassurance against future risk of precancer and cancer conferred by a negative human papillomavirus test. J Natl Cancer Inst. 2014;106(8).
  2. Kim JJ. Practice-based evidence for primary HPV testing in the United States. J Natl Cancer Inst. 2014;106(8).