Demystifying combined HPV-Pap screening guidelines, Part 2

Quick, how do you manage a patient when her Pap result is negative but the HPV screen is positive? If the answer isn't quite on the tip of your tongue, don't despair. During the past decade-and especially the last 3 years-it's been difficult to keep abreast of the explosion of information on the natural history of cervical dysplasia-along with related technology for detecting what we've now essentially nailed as the key culprit in causing cervical cancer: the human papillomavirus. In addition, ob/gyns have resisted integrating so many new screening guidelines into their practices, as discussed in Part 1 ("Cervical cancer guidelines: Making sense of the screening intervals," Contemporary OB/GYN 2006;51[April]:44-53). In fact, as recently as April, the American College of Obstetricians and Gynecologists issued yet another document to vie for our attention-a new Committee Opinion on cervical cytology in adolescents!¹ Despite our reluctance to embrace change, to better serve our patients, it's crucial that we understand the rationale behind each guideline-beginning with the combined screening option for women aged 30 and older-so we can begin applying them to routine patient management.

My goal here is to demystify recent recommendations beginning with the primary cervical screening guidelines issued in 2002 by the American Cancer Society (ACS) and in 2003 by ACOG.^2,3 We'll also tackle "Interim guidance on the use of HPV testing in primary screening" and ACOG Practice Bulletin Number 61."^4,5

Reviewing the rationale for extending intervals

In Part I, we discussed extending the screening interval for women aged 30 and over who have more than three consecutive normal Pap tests. Let's look now at another screening option for this same group of women for whom combined HPV/Pap testing can be very reassuring.

Extending the interval: a negative HPV test and a normal Pap

The combined screening option now offered to women aged 30 and over is based on the strict association of high-risk HPV with CIN 3 and cervical cancer and an increasing body of studies on combined screening with an HPV test as an adjunct to the Pap. HPV testing is 25% to 40% more sensitive for detecting CIN 3+ than a conventional Pap smear and 10% to 15% more sensitive than liquid-based cytology.^7-10 Women negative on both a concurrent Pap and an HPV test are at exceedingly low risk for CIN 2,3+, estimated to be approximately one per 1,000.⁴ This very high reassurance extends not only for present disease, but also predicts low risk for many years in the future, providing the rationale for screening no more often than every 3 years.^2,3,11-13

Highly reassuring result. Because this level of reassurance is obtained from a single combined screen, the requirement for documenting three consecutive normal Pap results prior to extending the screening interval is unnecessary. This is particularly important because women screened infrequently with cytology alone are at highest risk for cervical cancer (second only to women never screened) and are therefore less likely to obtain the three consecutive negative/normal tests required for optimal protection. Screening women testing negative on both tests more often than every 3 years would be more likely to detect new transient HPV infections, significantly increasing cost without benefit and risking overtreatment of many women who have only transient HPV infections.¹⁴