The HART (HPV in Addition to Routine Testing) study suggests that screening women for human papillomavirus and then triaging those who are positive with cytology may improve detection rates of high-grade cervical intraepithelial neoplasia (CIN2+) without increasing the rate of colposcopies.
HART was a British multicenter screening study involving more than 11,000 women between 30 and 60 years of age from 161 family practices. The researchers randomized women with borderline cytology and women positive for high-risk HPV with negative cytology to receive either immediate colposcopy or repeat HPV testing, cytology, and colposcopy in 12 months.
In terms of detecting CIN2+, the authors found HPV testing to be considerably more sensitive than borderline or worse cytology (97.1% vs. 76.6%, respectively), and only slightly less specific (93.3% vs. 95.8%). They also found 12-month surveillance of HPV-positive women with negative or borderline cytology to be as effective as immediate colposcopy.
In addition, they determined that HPV testing is more sensitive than cytology in detecting atypical squamous cells of undetermined significance, and that it has the potential to reduce the rate of colposcopy referrals for mild dyskaryosis.1
An accompanying editorial in the same issue of the Lancet points out that while Pap cytology screening has successfully cut the incidence of cervical cancer by about 75%, Pap testing has a sensitivity of only about 51% and a high false-negative rate. The author also explains that the concept of serial diagnostic testing (with first a highly sensitive test followed by a highly specific one to triage) has good precedent in other areas of medicine, such as testing for syphilis. And finally, he supports shifting the focus of screening from a morphology-based approach to one that searches for the sexually transmitted cause, remarking that placing "the emphasis of prevention not only on women but on their partners as well" is long overdue.2
1. Cuzick J, Szarewski A, Cubie H, et al. Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet. 2003;362:1871-1876.
2. Franco EL. Are we ready for a paradigm change in cervical cancer screening? Lancet. 2003;362:1866-1867.