The Positive Predictive Value of Cervical Smears in Previously Screened Postmenopausal Women: The Heart and Estrogen/progestin Replacement Study (HERS)

19 December 2000 | Volume 133 Issue 12 | Pages 942-950

Background: The benefits and risks of performing annual cervical smears on postmenopausal women are not well defined. The independent effect of hormone 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 oral 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 significance, low-grade squamous epithelial lesion, and high-grade squamous epithelial lesion) and final histologic diagnoses.

Results: The incidence of new cytologic abnormalities in the 2 years following 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 histologic diagnoses, one had mild to moderate dysplasia. The positive predictive 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 predictive 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 women, the incidence of cytologic abnormalities was nonsignificantly higher (relative hazard, 1.36 [CI, 0.93 to 1.99]), largely because of a nonsignificant 58% greater incidence of atypical squamous cells of undetermined significance (relative hazard, 1.58 [CI, 0.99 to 2.52]).

Conclusions: Because of a poor positive predictive value, cervical smears should not be performed within 2 years of normal cytologic results in postmenopausal women. Therapy with oral estrogen plus progestin does not significantly affect the incidence of cytologic abnormalities.

Author and Article Information

From the University of California, San Francisco, San Francisco, California; University of Minnesota, Minneapolis, Minnesota; Medical College of Wisconsin, Milwaukee, Wisconsin; Johns Hopkins University, Baltimore, Maryland; Wake Forest University School of Medicine, Winston-Salem, North Carolina; Wyeth-Ayerst Research, Radnor, Pennsylvania; Cedars-Sinai Medical Center, Los Angeles, California; and Georgetown University Medical Center, Washington, D.C.

Grant Support: In part by grants from the Rhoda Goldman Fund of Mount Zion Health Systems, San Francisco, California; the 1997–1998 American College of Obstetricians and Gynecologists/Solvay Pharmaceuticals, Inc., Research Award in Menopause; the National Cancer Institute (K08 CA 74973-02); the National Institute on Aging (AG 15340); and the Agency for Healthcare Research and Quality (HS07373). The Heart and Estrogen/progestin Replacement Study was funded by Wyeth-Ayerst Research. Dr. Grady has received research funding and Drs. La Valleur, Barnabei, and Snyder have received honoraria from Wyeth-Ayerst Research. Dr. Pickar is a senior scientist at Wyeth-Ayerst Research.

Current Author Addresses: Dr. Sawaya: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, 3333 California Street, Suite 335, San Francisco, CA 94143-0856.

Drs. Grady and Kerlikowske: Department of Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121.

Dr. La Valleur: Department of Obstetrics and Gynecology, 420 Delaware Street SE, Minneapolis, MN 55455.

Dr. Barnabei: Medical College of Wisconsin, Department of Obstetrics and Gynecology, 9200 West Wisconsin Avenue, Milwaukee, WI 53226.

Dr. Bass: Fertility Center of Maryland, 110 West Road, Suite 102, Towson, MD 21204.

Dr. Snyder: Wake Forest University School of Medicine, Department of Obstetrics and Gynecology, Medical Center Boulevard, Winston-Salem, NC 27157.

Dr. Pickar: Wyeth-Ayerst Research, Box 42528, Philadelphia, PA 19101.

Dr. Agarwal: Department of Obstetrics and Gynecology, Suite 160W, Cedars-Sinai Medical Center, Los Angeles, CA 90048.

Dr. Mandelblatt: Georgetown University Medical Center, Department of Oncology, Lombardi Cancer Center, 2233 Wisconsin Avenue, Suite 440, Washington, DC 20007.

Author Contributions: Conception and design: G.F. Sawaya, D. Grady, K. Kerlikowske, J. La Valleur, J.H. Picker, J. Mandelblatt.

Analysis and interpretation of the data: G.F. Sawaya, D. Grady, K. Kerlikowske, V.M. Barnabei, J.H. Picker, J. Mandelblatt.

Drafting of the article: G.F. Sawaya, K. Kerlikowske, J. La Valleur, V.M. Barnabei, S.K. Agarwal, J. Mandelblatt.

Critical revision of the article for important intellectual content: G.F. Sawaya, D. Grady, K. Kerlikowske, J. La Valleur, V.M. Barnabei, K. Bass, T.E. Snyder, J.H. Picker, S.K. Agarwal, J. Mandelblatt.

Final approval of the article: G.F. Sawaya, D. Grady, K. Kerlikowske, J. La Valleur, V.M. Barnabei, K. Bass, T.E. Snyder, S.K. Agarwal, J. Mandelblatt.

Provision of study materials or patients: D. Grady, T.E. Snyder.

Statistical expertise: G.F. Sawaya.

Obtaining of funding: G.F. Sawaya, D. Grady, J. Mandelblatt.

Administrative, technical, or logistic support: G.F. Sawaya, D. Grady, S.K. Agarwal.

Collection and assembly of data: G.F. Sawaya, D. Grady, K. Bass, S.K. Agarwal.