Atypical squamous cells, cannot exclude a high-grade intraepithelial lesion and its clinical significance in postmenopausal, pregnant, postpartum, and contraceptive-use patients.

Background: Previous studies have confirmed the low predictive value of a diagnosis of atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion (ASC-H) in a Papanicolaou (Pap) smear for subsequent high-grade dysplasia in the postmenopausal age group. It appears plausible that the decrease in estrogen inherent in the postmenopausal state likely produces reactive cytologic atypia, which is misinterpreted as ASC-H. The change in hormone levels observed in pregnant patients, postpartum patients, and contraceptive users, as a corollary, potentially could create a similar diagnostic dilemma. In the current study, the impact of age and altered hormone status on the frequency of ASC-H was assessed to answer the following questions: Is the low predictive value of ASC-H in postmenopausal women an age-related phenomenon, and do other states that result in decreased levels of estrogen relative to progesterone have a similar association?

Methods: Pap smears that were diagnosed as ASC-H were divided into postmenopausal, pregnant, postpartum, and contraceptive-use categories. Each Pap smear slide was reviewed to assess the degree of atrophy and the character of atypical cells. The frequency of high-grade follow-up (histology and/or Digene Hybrid Capture II) in the postmenopausal group was compared with the frequency of high-grade follow-up in the pregnant, postpartum, and contraceptive-use categories using the chi-square test. The pregnant, postpartum, and contraceptive-use categories also were compared statistically among each other with the chi-square test.

Results: In total, 195 cases met the criteria for study inclusion. The percentage of patients who had subsequent high-grade follow-up was 22.5% in the postmenopausal group, 79.6% in the pregnant group, 66.7% in the postpartum group, and 60% in the contraceptive-use group. When these data were subjected to the chi-square test, there was a statistically significant difference (P<.0001) between the predictive value of subsequent high-grade follow-up in the postmenopausal group compared with the other patient groups. When the chi-square test was applied to the intercomparison of the pregnant, postpartum, and contraceptive-use categories, there were no significant differences (P > .05) in high-grade follow-up between any of these groups.

Conclusions: The diagnosis of ASC-H in postmenopausal Pap smears has a low predictive value in the subsequent diagnosis of high-grade squamous lesions in stark contrast to the pregnant, postpartum, and contraceptive-use categories. This suggests that age rather than hormone alterations affects the capacity of ASC-H to predict subsequent high-grade squamous intraepithelial lesions. In addition, there are no definite cytomorphologic criteria that can be used to distinguish reliably between benign cellular changes and possible high-grade squamous lesions in these Pap smears. Digene Hybrid Capture II testing, although helpful, does not have 100% correlation with subsequent tissue/Pap smear follow-up and cannot be used alone to triage this group of women for colposcopy.