UPDATE ON CERVICAL DISEASE

Screening can be made more cost-effective by extending the screening interval. One option is to repeat the Pap every 2 or 3 years, instead of annually, for women who have had three consecutive normal Pap tests. The additional risk of cervical cancer that results from extending the screening interval to 3 years is estimated to be 3 to 5 cases for every 100,000 women³ —numbers that are small but that are unacceptable to many, considering the great potential for preventing cervical cancer.

The other option is to add HPV testing to screening. Because an HPV test is more sensitive for CIN 2,3, a negative result provides long-lasting reassurance against cancer risk.

Enter, economics. Adding an HPV test to the screen without increasing the interval is not cost-effective: It increases overdiagnosis and overmanagement and, thereby, harm.

Moving to less frequent screening is the only option for improving the cost effectiveness of cervical cancer prevention; less frequent screening reduces not only 1) the number of tests but also 2) detection of transient HPV infections not destined to progress and 3) overmanagement and treatment of such benign infections. And the high sensitivity and long-term predictive value of an HPV test ensures that moving to a longer interval isn’t likely to put women at more risk even if the next screen exceeds 3 years. Major studies confirm this margin of safety and validate a move to less frequent screening. Here’s what we learned in the past year.

In search of an optimal protocol

Most research on co-testing continues to come from Europe, where organized screening programs have facilitated large studies.

Compared with screening by cytology alone, co-testing that included 1) referral to colposcopy of all women who had an abnormal Pap and 2) testing for type-specific HPV persistence at 12 months for women who initially had a normal Pap and a positive HPV test resulted in a 35% increase in sensitivity for detecting CIN 3+, with only a modest reduction in positive predictive value. The researchers noted, however, that the gain in sensitivity came at the expense of doubling screening tests because screening in Sweden already occurs at a 3-year interval.

Naucler and colleagues used the database from the intervention arm (n=6,257 women) of a population-based randomized trial (the Swedescreen Trial), in which a conventional Pap smear and HPV test were obtained from women 32 to 38 years old, to evaluate the efficacy of 10 cervical screening strategies based on HPV DNA testing alone, cytology alone, and co-testing with both tests.

Solomon and co-workers estimated that, in the very near future, 75 million Paps will be performed each year if we don’t change our screening strategy from annual cervical cytology. If all screened women younger than 30 years had a liquid-based Pap every 2 years as recommended by the ACS, however, and if all screened women 30 years or older had a Pap test and an HPV test every 3 years, the number of annual Paps would decline to 34 million. Because this protocol requires a similar number of HPV tests for women older than 30 years, the total number of primary screening tests (HPV + Pap tests) would be only marginally less than the Paps performed at the present interval. But it is expected that less frequent screening would also reduce the number of transient HPV-induced cytologic events detected that require follow-up.

Are there other options?

Additional savings are possible if 1) both the Pap test and the HPV test did not need to be performed together or 2) the screening interval could be longer than Solomon described.

Naucler and colleagues clearly demonstrated that the most effective of the 10 screening options they evaluated was screening with an HPV test first (the most sensitive test) followed by a Pap test (the most specific test) only on women who have a positive HPV test. This protocol increased the sensitivity for CIN 3+ by 30% over the detection rate when the Pap was the only screening test, maintained a high positive predictive value, and increased the number of screening tests over the triennial “Pap-only” protocol by just 12%. In the United States, this approach would significantly decrease the number of screening tests, and should decrease costs, compared with the number of tests and costs associated with the traditional annual Pap test.

However, whether co-testing will ever be replaced by an HPV test as the sole primary screen depends on whether we are willing to accept a small decrement in protection in exchange for a major gain in cost effectiveness. In the past, safety has trumped but, in every aspect of health care to come, this will be the trade-off debated if, as a nation, we are to make our health care more affordable.