The use of reflex high-risk human papillomavirus testing for atypical squamous cells of undetermined significance interpretations on vaginal specimens.

BACKGROUND: The use of reflex high-risk human papillomavirus (hrHPV) testing as a triage method for cervical specimens with an interpretation of atypical squamous cells of undetermined significance (ASC-US) is well established. To the authors' knowledge, very little has been reported regarding the utility of this approach in vaginal specimens in women with a prior hysterectomy. The current study evaluated the results of hrHPV testing in women with vaginal specimens interpreted as ASC-US in the authors' laboratory. METHODS: Follow-up information, including results of hrHPV testing, was sought for all vaginal smears reported as ASC-US from the authors' cytology laboratory during the calendar years 2005 and 2006. RESULTS: For the 2 years reviewed, 254 ASC-US vaginal specimens were available for assessment. Reflex hrHPV testing was requested on 236 (92.9%), with sufficient residual material available in 193 specimens. hrHPV was detected in 44 (22.8%). Follow-up results were available for 136 specimens, with a squamous intraepithelial lesion (SIL, all but 1 of which was low grade) found to be present in 21 (15.4%). SIL was identified in significantly more women in whom hrHPV was detected compared with those in whom hrHPV was not detected (41.9% vs 4.2%; P < .001 by the Fisher exact test). CONCLUSIONS: Rates of detection of squamous abnormalities in women with ASC-US on vaginal preparations in whom hrHPV was detected were found to be higher than in those without hrHPV. These findings suggest that clinical follow-up is needed for women in whom hrHPV is detected. hrHPV testing may be clinically useful as a method of triage for women with ASC-US vaginal smears.

The significance of high-risk human papillomavirus detection in women aged > or = 50 years with atypical squamous cells of undetermined significance cytologic preparations.

BACKGROUND: The use of high-risk human papillomavirus (HRHPV) testing in the triage of women with a cytologic diagnosis of atypical squamous cells of undetermined significance (ASC-US) has gained widespread acceptance. To date, very little has been reported on the significance of the detection of HRHPV in elderly women. METHODS: Results of HRHPV testing performed on women aged > or =50 years were examined for a 20-month period. Reflex testing for HRHPV was performed on residual liquid-based cytology specimens from women who were diagnosed with ASC-US by using the Digene Hybrid Capture method. Follow-up information on women who had HRHPV detected was obtained from subsequent pathology reports (cytology and surgical). RESULTS: HRHPV testing was performed on 762 specimens from women aged > or =50 years; virus was detected in 105 specimens (13.8%), and follow-up was available in 63 of those women (60%). Follow-up results included negative tests in 32 women (50.8% of those with follow-up available), low-grade squamous intraepithelial lesion in 26 women (41.3%), and high-grade squamous intraepithelial lesion (HSIL) in 5 women (7.9%). No glandular neoplasia or invasive carcinoma was identified. Relative light units/cutoff (RLU/CO) values ranged from 1 RLU/CO to 1705 RLU/CO; no significant associations were identified between RLU/CO values and follow-up results. CONCLUSIONS: Although HRHPV was detected in a minority of samples, HSIL was present in 7.9% of those with HRHPV. This confirms that the presence of HRHPV in women aged > or =50 years with ASC-US specimens needs clinical follow-up. There were no significant differences in RLU/CO values between women with positive versus negative follow-up to allow for further discrimination for follow-up.

Normal endometrial cells in liquid-based cervical cytology specimens in women aged 40 or older.

OBJECTIVE: The 2001 Bethesda System consensus statement directs the reporting of endometrial cells on cervical cytologic preparations in women aged 40 years or older. Our objective was to assess the significance of endometrial cells on cervical liquid-based cytology (LBC) specimens in this population. METHODS: The population included women aged 40 years or older in whom endometrial cells were identified in otherwise normal LBC specimens from December 2001 through June 2005, and who subsequently underwent endometrial sampling within a 12-month period. Patient age, menopausal status, hormonal use, the presence or absence of co-incident symptoms and endometrial sampling results were recorded. RESULTS: Endometrial cells were identified on LBC specimens in 2494 women during the study period, for an incidence of 0.4%. Of these, 370 women underwent endometrial sampling within 12 months of the incident LBC preparation and met inclusion criteria. In asymptomatic premenopausal women, sampled solely due to the presence of endometrial cells, 2.1% were identified with significant endometrial pathology, compared to 2.6% of symptomatic premenopausal women. In menopausal women, only those with symptoms (mainly bleeding) had significant pathology on subsequent sampling (25%); none of the asymptomatic menopausal women were found to have hyperplasia or carcinoma. No significant differences were identified in premenopausal women according to the time of sampling during the menstrual cycle or use of oral contraceptives. CONCLUSION: Endometrial cells on LBC preparations, even in the absence of symptoms in premenopausal women aged 40 years or older, are associated with significant uterine pathology.

Characterization of human leukocyte antigen-G (HLA-G) expression in endometrial adenocarcinoma.

OBJECTIVES: The current study sought to determine if endometrial adenocarcinomas express human leukocyte antigen-G (HLA-G), an immune-regulatory protein, and if degree of expression correlates with the stage of carcinoma. METHODS: Forty-four primary endometrial adenocarcinomas were tested using immunohistochemical staining with the 4H84 anti-HLA-G monoclonal antibody. Metastatic implants were not included. A subset of 10 samples was tested using RNA in situ hybridization to confirm the presence of HLA-G transcript. Results of staining were analyzed with respect to grade, tumor histology, and stage of disease. Spearman rank correlation was used to assess tumor grade, histology, and disease stage as a function of HLA-G protein staining. Receiver-operator characteristic (ROC) curve analysis was used to determine the feasibility of HLA-G protein staining as a clinical marker for advanced stage disease. RESULTS: Immunohistochemical staining for HLA-G protein was seen in 55% (24/44) of primary site endometrial adenocarcinomas and localized to glandular but not stromal epithelium. RNA in situ hybridization confirmed the presence of transcript in the majority of samples tested and also localized to glandular epithelium. A significant correlation was seen with increasing HLA-G protein staining and increasing stage of endometrial cancer, P < 0.01. HLA-G was found to be a fair discriminator as a test for metastatic disease with an area under the ROC curve of 0.75 for metastatic versus non-metastatic disease. CONCLUSIONS: HLA-G protein is expressed in a significant number of endometrial adenocarcinomas, in which it is localized to the glandular epithelium. HLA-G may serve as a clinical marker for the preoperative prediction of metastatic endometrial cancer.

Reflex high-risk human papillomavirus testing for women with atypical squamous cells of undetermined significance in cytologic smears: effects since implementation in a large clinical practice.

Reflex high-risk human papillomavirus (HPV) testing often is used in the management of women with atypical squamous cells of undetermined significance identified in cervicovaginal screening. Following implementation of reflex testing, our laboratory processed 8,022 specimens during a 20-month period; sufficient material was available for testing in 7,334 specimens. High-risk HPV was detected in 34.10% of these specimens. Detection rates varied with age, with positive rates as high as 58.46% in women 20 years old or younger, decreasing to 14.58% in women older than 35 years. The detection rate, categorized in 5-year age increments, showed a significant decrease until after 35 years, when the rate remained fairly constant (P < .0001). The detection rate decreased over the time of the study. These results demonstrate that high-risk HPV detection might vary according to the age mix of the population tested and the interval after implementation of testing.

Asian-Pacific Islander race independently predicts poor outcome in patients with endometrial cancer.

OBJECTIVE: The Department of Defense health care system provides access to care without respect to age, race, or socioeconomic status. We sought to determine the effect of race as a predictor of survival in patients with endometrial cancer treated in the Department of Defense medical system. METHODS: Information on patients with endometrial carcinoma was extracted from the Department of Defense centralized tumor registry for the period 1988 to 1995. Data included age at diagnosis, military status, race, tumor histology, grade, FIGO surgical stage, adjuvant therapies, and disease-free survival. The chi(2) test was used for analysis of prognostic factors and adjuvant treatments between racial groups. Actuarial survival curves were calculated by using the method of Kaplan and Meier and compared by the log-rank test. Variables found to be significant on univariate analysis (P < 0.05) were entered into a multivariate Cox regression analysis. RESULTS: Of 1811 patients meeting criteria for the study, racial distribution was 90% Caucasian, 4.4% African-American, and 5.5% Asian-Pacific Islander. African-Americans had more advanced stages of disease compared to Caucasians (P < 0.001). Both African-Americans and Asian-Pacific Islanders had higher grade tumors and less favorable histologic types than Caucasians (P < 0.05). The extent of adjuvant therapies was similar for racial groups. African-Americans and Asian-Pacific Islanders had significantly worse 5-year disease-free survivals than Caucasians (P = 0.007). Additional poor prognostic factors included age >60 years, grade, unfavorable histology, and stage. On multivariate analysis age >60 years, stage, and Asian-Pacific Islander race remained significant prognostic factors. CONCLUSION: African-Americans and Asian-Pacific Islanders had worse survivals than Caucasians. After controlling for imbalances in clinicopathologic factors, Asian-Pacific Islander race was found to be a newly identified poor prognostic factor.

The significance of psammoma bodies that are found incidentally during endometrial biopsy.

OBJECTIVE: The purpose of this study was to elucidate the significance of psammoma bodies that are found incidentally during endometrial biopsy. STUDY DESIGN: We reviewed the medical records of 11 women who were found to have psammoma bodies during endometrial biopsy over an 18-month period and extracted data that included demographic information, extent of evaluation, and pathologic findings. RESULTS: Ten women were postmenopausal and underwent endometrial biopsy for abnormal uterine bleeding while using combined hormone replacement. Most women underwent dilation and curettage with hysteroscopy plus either laparoscopy or ultrasonography. Notable findings included: 5 women with endometrial polyps, 2 women with endometriosis, 1 woman with endosalpingiosis, and 1 woman with a mature cystic teratoma. No endometrial or adnexal malignancies were identified. CONCLUSION: This series represents the largest series to date regarding psammoma bodies that have been found incidentally during endometrial biopsy. All psammoma bodies were associated with benign findings. Further evaluation of the endometrial cavity with hysteroscopy or sonohysterography, plus some form of adnexal assessment, is a reasonable definitive evaluation scheme.

Association of CD44 isoform immunohistochemical expression with myometrial and vascular invasion in endometrioid endometrial carcinoma.

OBJECTIVE: Appropriate clinical management of cases of FIGO Grade I and II endometrial carcinoma relies heavily on the determination of myometrial invasion (MI). There are no reports addressing expression of the cell adhesion molecule CD44 in the subset of Grade I and II endometrioid carcinoma (EC) as it relates to prognosis, including MI. METHODS: Immunohistochemical staining for CD44s and CD44v6 was evaluated in 40 hysterectomy specimens with Grade I and II EC, including 11 noninvasive ECs, 14 with MI <50% of myometrial thickness, and 15 with deep invasion (MI >50%). Staining characteristics according to the presence of MI and vascular space invasion (VSI) were evaluated. Strong membranous staining of >10% of tumor cells was interpreted as positive. RESULTS: CD44v6 staining was positive in 20% (8/40) of cases, including 45% (5/11) of EC without MI but only 10% (3/29) with MI (P = 0.025). CD44v6 staining was not present in deeply invasive tumors (0/15), while it was present in 8/25 superficially or noninvasive tumors (P = 0.016). Sensitivity and specificity were 25 and 100%, respectively, using CD44v6 in evaluating deep myometrial invasion. CD44s showed a trend toward positive staining when comparing noninvasive versus invasive tumors and noninvasive/superficially invasive versus deeply invasive tumors (P = 0.08 and 0.12, respectively). CD44s or CD44v6 staining was highly specific for absence of VSI, although statistical comparison did not reach significance. CONCLUSION: Deeply invasive EC was associated with a consistent lack of CD44v6 expression. This may have potential clinical utility if this finding is demonstrated in further study of prehysterectomy sampling specimens containing EC.