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 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.


METHODS
Prospective cohort study (incidence) and randomized, double-blind, placebo-controlled trial (hormone therapy).


METHODS
20 U.S. outpatient and community clinical centers.


METHODS
2561 women with a uterus and normal cytologic characteristics at baseline.


METHODS
Annual smears; oral conjugated equine estrogens, 0. 625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or identical placebo.


METHODS
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.
Sawaya
G F
GF
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, 3333 California Street, Suite 335, San Francisco, CA 94143-0856, USA.
Grady
D
D
Kerlikowske
K
K
Valleur
J L
JL
Barnabei
V M
VM
Bass
K
K
Snyder
T E
TE
Pickar
J H
JH
Agarwal
S K
SK
Mandelblatt
J
J
D000368:Aged; D002584:Cervix Uteri / Q000187:drug effects* / Q000473:pathology*; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects*; D005189:False Positive Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects*; D017698:Postmenopause; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D002578:Uterine Cervical Dysplasia / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000473:pathology; D014626:Vaginal Smears
D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate