Adding Human Papillomavirus Testing to Cytology for Primary Cervical Cancer Screening: Shooting First and Asking Questions Later

Annual cervical cancer screening is a well-established and highly effective routine practice in the United States (1), but it is also inefficient and expensive (2). A more streamlined approach would be to stratify women by risk and adjust the frequency of screening accordingly: Screen low-risk women infrequently, thereby minimizing the harms of screening, while focusing attention and resources on those at higher risk. Because oncogenic types of human papillomavirus (HPV) cause cervical neoplasia, HPV testing is a prime candidate to risk-stratify women for screening.

Several different HPV tests are used worldwide, but in the United States, the only commercially available test approved by the U.S. Food and Drug Administration is Hybrid Capture 2 (Digene, Gaithersburg, Maryland), an assay that detects DNA from 1 or more of 13 oncogenic HPV types. To perform this test, a cervical specimen is obtained at the time of speculum examination and is either placed in a transport medium or, if liquid-based cytology is used, a vial of liquid preservative. In the laboratory, the specimen is treated with a base solution to release oncogenic HPV DNA, if present. Specific RNA probes are added that combine with DNA to create RNA–DNA hybrids; these are captured onto a solid phase coated with antibodies specific to the RNA–DNA hybrid. Captured hybrids are detected with multiple antibodies conjugated with alkaline phosphatase; the resulting signal is amplified and detected by chemiluminescence.

In 2003, the U.S. Preventive Services Task Force considered the evidence regarding routine HPV testing to be insufficient to recommend for or against its use as a primary screening test for cervical cancer (3). Both the American Cancer Society (4) and the American College of Obstetricians and Gynecologists (5), however, defined an alternative to cytology screening alone in women older than 30 years of age that …