The positive predictive value of cervical smears in previously screened postmenopausal women: The Heart and Estrogen/progestin Replacement Study (HERS)

Background: The benefits and risks of performing annual cervical smears on postmenopausal women are not well defined. The independent effect of hormon e replacement therapy on development of cytologic abnormalities is unknown. Objective: To determine the positive predictive value of cervical smears in previously screened postmenopausal women and to determine the effect of or al estrogen plus progestin on incident cervical cytologic abnormalities. Design: Prospective cohort study (incidence) and randomized, double-blind, placebo-controlled trial (hormone therapy). Setting: 20 U.S. outpatient and community clinical centers. Participants: 2561 women with a uterus and normal cytologic characteristics at baseline. Interventions: Annual smears; oral conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or identical placebo. Measurements: Incident cytologic abnormalities (atypical squamous cells of undetermined significance, atypical glandular cells of undetermined signifi cance, low-grade squamous epithelial lesion, and high-grade squamous epithe lial lesion) and final histologic diagnoses. Results: The incidence of new cytologic abnormalities in the 2 years follow ing a normal smear was 110 per 4895 person-years (23 per 1000 person-years [95% CI, 18 to 27 per 1000 person-years]). Among the 103 women with known h istologic diagnoses, one had mild to moderate dysplasia. The positive predi ctive value of any smear abnormality identified 1 year after a normal smear , therefore, was 0% (CI, 0% to 5.0%) (0 of 78 women); the positive predicti ve value of abnormalities found within 2 years was 0.9% (CI, 0.0% to 3.0%) (1 of 110 women). In hormone-treated compared with non-hormone-treated wome n, the incidence of cytologic abnormalities was nonsignificantly higher (re lative hazard, 1.36 [CI, 0.93 to 1.99]), largely because of a nonsignifican t 58% greater incidence of atypical squamous cells of undetermined signific ance (relative hazard, 1.58 [CI, 0.99 to 2.52]). Conclusions: Because of a poor positive predictive value, cervical smears s hould not be performed within 2 years of normal cytologic results in postme nopausal women. Therapy with oral estrogen plus progestin does not signific antly affect the incidence of cytologic abnormalities.