Lower cost strategies for triage of human papillomavirus DNA-positive women.

Cervical cancer incidence and mortality have declined significantly in those places that have effectively implemented Papanicolaou (Pap) test-based screening.1 Yet cervical cancer remains the second most common female cancer and third most common cause of female cancer-related mortality globally, with an annual incidence of approximately 530,000 and mortality of 275,000, respectively.2 This seeming contradiction is explained by the fact that cervical cancer incidence and mortality are approximately 10-fold greater in low- and middle-income countries (LMIC), where Pap programs have failed to be established because of the technical and financial barriers to implementation.1,3 Because of these limitations, alternative screening strategies have been developed and evaluated, including molecular testing for the necessary cause of cervical cancer, carcinogenic human papillomavirus (HPV). DNA testing for HPV has been shown to be more sensitive4–9 and more reliable10–12 than Pap testing. A key attribute of HPV testing related to its high sensitivity is its excellent negative predictive value, providing near complete reassurance following a negative test that the woman does not have cancer or precancer.13–15 Thus, a negative HPV DNA test does an excellent job of screening by ruling out disease in the primarily healthy population, permitting fewer screens of the general population in lifetime. Affordable tests like careHPV™ (careHPV™; QIAGEN, Gaithersburg, MD)16 and “tiered pricing” of higher cost tests will make HPV testing increasingly more available to LMIC. However, the challenge of using HPV testing, or any screening test, is the management of screen-positive women, as most women with a positive screening test (∼80% to 90%) will not have concurrent disease (i.e., cervical precancer or cancer). This is an especially perplexing problem in LMIC, where there are limited numbers of clinics, colposcopists, pathologists and clinicians qualified to provide diagnosis and treatment, and services must be prioritized for women at highest risk for harboring precancer or cancer.17 In China, findings showed a higher prevalence of HR-HPV infection and CIN2+, which suggests that the burden of cervical cancer in China especially in some rural areas is more substantial than was previously reported with a much higher need for comprehensive screening and will result in many more HPV positive women to manage.18,19 Moreover, in the context of a screen-and-treat program, where treatment is provided without colposcopy or biopsy, it may be desirable to immediately treat only those at a higher risk of cervical precancer and cancer among the screen-positives to minimize overtreatment. In 2010, we launched a clinical study in 7,500 women living in rural China as part of the Screening Technologies to Advance Rapid Testing for Cervical Cancer Prevention—Utility and Program Planning (START-UP) Project. The stated goals of this study were to evaluate new strategies for screening and management of screen positives that might be employed in LMIC. Here, we report on our evaluation of different management or “triage” strategies for HPV DNA-positive women. We explored both visual and molecular methods to distinguish between HPV DNA-positive women at high and low risk of cervical precancer and cancer. Further management of the latter might be deferred until there is evidence of increased risk (e.g., HPV persistence),15,20,21 thereby increasing the “predictive value” of the intervention and decreasing the use of more invasive procedures and resources in lower-risk women.