Patton Amber L, Duncan Lisa, Bloom Leneord, Phaneuf Geneen, Zafar Nadeem
Pathology Department, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37920, USA.
Cancer. 2008 Dec 25;114(6):481-8. doi: 10.1002/cncr.23949.
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?
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.
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.
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.
既往研究已证实，巴氏涂片诊断为非典型鳞状细胞、不能排除高级别鳞状上皮内病变（ASC-H），对于绝经后年龄组后续高级别发育异常的预测价值较低。绝经状态下雌激素水平降低可能导致反应性细胞学非典型性，而这被误诊为ASC-H，这似乎是合理的。作为必然结果，在孕妇、产后妇女和避孕药使用者中观察到的激素水平变化，可能会造成类似的诊断困境。在本研究中，评估年龄和激素状态改变对ASC-H频率的影响，以回答以下问题：绝经后女性ASC-H的低预测价值是与年龄相关的现象吗？相对于孕激素导致雌激素水平降低的其他状态是否有类似的关联？
将诊断为ASC-H的巴氏涂片分为绝经后、怀孕、产后和避孕药使用类别。对每张巴氏涂片玻片进行复查，以评估萎缩程度和非典型细胞特征。使用卡方检验比较绝经后组高级别随访（组织学和/或Digene Hybrid Capture II）的频率与怀孕、产后和避孕药使用类别的高级别随访频率。怀孕、产后和避孕药使用类别之间也使用卡方检验进行统计学比较。
总共195例符合研究纳入标准。绝经后组后续进行高级别随访的患者百分比为22.5%，怀孕组为79.6%，产后组为66.7%，避孕药使用组为60%。当对这些数据进行卡方检验时，绝经后组与其他患者组相比，后续高级别随访的预测价值存在统计学显著差异（P<.0001）。当对怀孕、产后和避孕药使用类别进行相互比较时，这些组中任何一组的高级别随访均无显著差异（P>.05）。
绝经后巴氏涂片诊断为ASC-H在后续高级别鳞状病变诊断中的预测价值较低，这与怀孕、产后和避孕药使用类别形成鲜明对比。这表明年龄而非激素改变影响ASC-H预测后续高级别鳞状上皮内病变的能力。此外，在这些巴氏涂片中，没有明确的细胞形态学标准可用于可靠地区分良性细胞变化和可能的高级别鳞状病变。Digene Hybrid Capture II检测虽然有帮助，但与后续组织/巴氏涂片随访并非100%相关，不能单独用于对这组女性进行阴道镜检查分流。
