Atypical Glandular Cells Cytology Research Articles

The significance of extensive HPV genotyping for cervical high-grade neoplasia among women with atypical glandular cells.

To examine the associated risk of cervical intraepithelial neoplasm grade 3+ (CIN3+) lesions in patients with AGC and extensive human papillomavirus (HPV) genotyping. Cases with atypical glandular cell (AGC) interpretation on a Papanicolaou (Pap) test were identified along with associated extensive HPV genotyping and histologic follow-up results. Within this cohort of 469,694 Pap tests, 0.4% were diagnosed as AGCs. In total, 1267 cases had concurrent high-risk HPV (hrHPV) genotyping, and 40.3% were hrHPV positive. The percentage of AGC cases with cervical CIN3+ on histologic follow-up was 52.2% when hrHPV was positive, whereas it was 4.9% with a negative hrHPV result. The top 5 hrHPV genotypes associated with cervical CIN3+ in this cohort were HPV16, HPV18, HPV58, HPV52, and HPV33. Indeed, 92.8% of the hrHPV-associated CIN3+ lesions identified in this cohort were positive for at least one of these HPV genotypes. The sensitivity of detecting cervical CIN3+ lesions was 85.6% with the top 5 hrHPV genotypes (HPV16/18/58/52/33) and only increased to 89.0% when the additional 12 genotypes were included. In patients with an AGC Pap, the risk of having a cervical CIN3+ lesion is greatly increased by positivity for hrHPV types 16, 18, 58, 52, and/or 33. Incorporating comprehensive HPV genotyping into AGC cytology allows for refined risk stratification and more tailored management strategies.

Correlation of immediate prevalence of cervical precancers and cancers with HPV genotype and age in women with atypical glandular cells cytology: A retrospective analysis of 369 cases.

This study aims to assess the immediate risk of cervical precancers and cancers in women with atypical glandular cells (AGC) cytology, based on high-risk human papillomavirus (hrHPV) genotypes and age. A retrospective analysis was conducted on 369 cases of AGC with immediate follow-up biopsy results, including 299 AGC-not otherwise specified (NOS) and 70 AGC-favor neoplastic (FN). Among the 369 AGC cases, 127 tested positive for hrHPV (34.4%). The predominant high-risk type was other 11 genotypes (44.1%), followed by 16+ (29.1%), 18/45+ (26.0%), and 16 and 18/45 double-positive (0.79%). Precancers and cancers were detected in 30.4% (112 of 369) and 9.8% (36 of 369) of cases, respectively. The HPV-18/45+ group had notably higher adenocarcinoma in situ and adenocarcinoma (AIS+) prevalence compared to other 11 genotype groups (p<.0001 and p=.001, respectively). The HPV-16+ group showed significantly higher high-grade cervical squamous epithelial lesion and squamous cell carcinoma prevalence than other 11 genotype groups (p<.0001 and p=.017, respectively). Using 40-year cutoff, older women had significantly higher prevalence of abnormal glandular lesion+lesions (17.6% vs. 7.6%, p=.005) and adenocarcinoma (AC) (12.4% vs. 2.5%, p=.001). Using 50-year cutoff, older women had higher prevalence of squamous cell carcinoma (SCC) (3.3% vs. 0.4%, p=.042) and AC (15.2% vs. 5.8%, p=.005). Subgroup analysis revealed that AGC-FN women showed more severe cervical pathology than AGC-NOS women (p<.001). AGC women have a significantly increased risk of cervical precancerous lesions and cancer. HPV genotyping and patient age factors need to be taken into consideration in the clinical management process of AGC patients.

The combined finding of HPV 16, 18, or 45 and cytologic Atypical Glandular Cells (AGC) indicates a greatly elevated risk of in situ and invasive cervical adenocarcinoma

BackgroundCervical screening has not effectively controlled cervical adenocarcinoma (AC). Human papillomavirus (HPV) testing is recommended for cervical screening but the optimal management of HPV-positive individuals to prevent AC remains a question. Cytology and HPV typing are two triage options to predict the risk of AC. We combined two potential biomarkers (atypical glandular cell, AGC, cytology and HPV-types 16, 18, or 45) to assess their joint effect on detecting AC. MethodsKaiser Permanente Northern California (KPNC) used triennial co-testing with cytology and HPV testing (positive/negative) for routine cervical screening between 2003 and 2020. HPV typing of a sample of residual HPV test specimens was performed on a separate cohort selected from KPNC (Persistence and Progression, PaP, cohort). We compared risk of prevalent and incident histologic AC/AIS (adenocarcinoma in situ) associated with preceding combinations of cytologic results and HPV typing. Risk of squamous cell cancer (SCC)/cervical intraepithelial neoplasia grade 3 (CIN3) (SCC/CIN3) was also included for comparison. ResultsAmong HPV-positive individuals in PaP cohort, 99% of prevalent AC and 96% of AIS were linked to HPV-types 16, 18, or 45 (denoted HPV 16/18/45). Although rare (0.09% of screening population), the concurrent detection of HPV 16/18/45 with AGC cytology predicted a highly elevated relative risk of underlying histologic AC/AIS; the absolute risk of diagnosing AC/AIS was 12% and odds ratio (OR) was 1341 (95%CI:495–3630) compared to patients with other high-risk HPV types and normal cytology. Cumulatively (allowing non-concurrent results), approximately one-third of the AC/AIS cases ever had HPV 16/18/45 and AGC cytology (OR = 1785; 95%CI:872–3656). AGC was not as strongly associated with SCC/CIN3. ConclusionDetection of HPV 16/18/45 positivity elevates risk of adenocarcinoma, particularly if AGC cytology is also found.

P16/Ki-67 Dual Staining in Positive Human Papillomavirus DNA Testing for Predictive Diagnosis of Abnormal Cervical Lesions in Northeastern Thai Women.

Cervical cancer screening can effectively reduce new cervical cancer cases, including in Thailand. The abnormal results are subsequently referred for colposcopy. To avoid unnecessary colposcopy, an efficient triage is still needed for validation. This study aimed to investigate the overall positivity of cytology-based screening, HPV detection, and p16/Ki-67 dual staining and evaluate different triage strategies for predictive diagnosis of abnormal cervical lesions in northeastern Thailand. Cervical cells were collected from 191 women who came for cervical screening in the gynecological outpatient department during March 2019-February 2020. Pap smear samples were classified into 6 groups including 17 atypical glandular cells (AGC), 21 atypical squamous cells of undetermined significance (ASC-US), 7 atypical squamous cells - cannot exclude HSIL (ASC-H), 26 low-grade squamous intraepithelial lesions (LSILs), 19 high-grade SILs (HSILs) and 101 no squamous intraepithelial lesion (noSIL). Polymerase chain reaction (PCR) was performed for HPV DNA detection. HPV genotyping was determined by reverse line blot hybridization. P16/Ki-67 dual staining was performed by using CINtec PLUS Cytology kit. Biopsies from abnormal screening were collected for surgical pathology classification. High-risk HPV (HR-HPV) infection was 2.97%, 29.41%, 38.10%, 57.14%, 46.15% and 84.21% in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL cytology respectively. P16/ Ki-67 in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL was 0.99%, 5.88%, 9.52%, 42.86%, 26.92% and 63.16%, respectively (P-value < 0.001). Among p16/Ki-67 positive cases, 96.15% (25/26) were infected with HPV and 84.62% (22/26) were HR-HPV. The overall positivity of each and co-testing between cytology or HPV DNA testing or p16/Ki-67 dual staining was evaluated. In each cervical lesion, primary HPV DNA testing showed the highest sensitivity, but low specificity. The combined all HPV/HR-HPV with p16/Ki-67 detection increased the specificity of abnormal cervical lesions. P16/Ki-67 dual stain cytology in HPV-positive women performs well for diagnosis of abnormal cervical lesions and should be considered for management of HPV-positive women to avoid unnecessary colposcopy referrals.

Preventing Uterine Cervix Cancer: The Clinical Meaning of Atypical Glandular Cells.

To determine the prevalence of the atypical glandular cells (AGCs) cytology and to analyze its clinical significance in different age ranges. Retrospective observational study using computerized data from the Brazilian National Cancer Institute, including women screened between January 2002 and December 2008. The women included were those with an AGC result who were properly followed-up with colposcopy and a second cytology. A total of 132,147 cytopathological exams were performed during the study period. Five-hundred and thirty-three (0.4%) women with AGC cytology were identified and, of these, 69.41% (370/533) were properly referred for colposcopy and a new cytology. Most of the women (79.2%) with a 1st or 2nd AGC cytology were between the ages of 25 and 54 years. The 2nd cytology demonstrated 67.6% (250/370) of normality, 24.5% (91/370) of squamous atypia, and 6.2% (23/370) of AGC, 0.8% (3/370) adenocarcinoma in situ and 0.8% (3/370) adenocarcinoma invasor. On biopsy of the women with a second AGC cytology, 43.4% (10/23) had normal histology, 43.4% (10/23) had squamous lesions, 8.7% (2/23) had invasive adenocarcinoma, and 1.2% (1/23) had an inconclusive report. All of the women with high-grade squamous intraepithelial lesion (HSIL) or invasive adenocarcinoma (respectively 5 and 2 patients), after a 2nd AGC cytology were 25 years old or older. The prevalence of the AGC cytology was low in the studied population. Most of the AGC cytology cases occurred in adult women between the ages of 25 and 54. Although most of the patients had normal histology after follow-up, several of them presented with squamous intraepithelial lesions or invasive adenocarcinoma.

The relationship of human papillomavirus and cytology co-testing results with endometrial and ovarian cancer diagnoses

BackgroundTo investigate whether routine cervical screening using human papillomavirus (HPV) and cytology co-testing effectively identifies women with endometrial (EC) or ovarian (OvC) cancer. MethodsIn 2003, Kaiser Permanente Northern California implemented triennial co-testing in women aged ≥30 years. Index screening results (n = 2,385,729) were linked to subsequent EC (n = 3434) and OvC (n = 1113) diagnoses from January 1, 2003 to December 31, 2017. EC were categorized as type 1 or 2, and, selectively, EC and OvC diagnoses were stratified on whether symptoms were present at the time of the co-test. Fractions and absolute risks of EC or OvC of each co-testing result were calculated. ResultsMost EC (82.18%) and OvC (88.68%) were preceded by a negative HPV and negative cytology co-test. More EC were preceded by atypical squamous cells of undetermined significance (ASC-US) or more severe (ASC-US+) cytology and negative HPV test (n = 290) (8.44% of EC) compared to a negative cytology and a positive HPV test (n = 31) (0.89% of EC) (p < 0.001). The absolute risk of any EC diagnosis following ASC-US+ and negative HPV test was 0.48%. Atypical glandular cells (AGC) cytology and a negative HPV result preceded 6.92% of any EC diagnosis, with an absolute risk of 4.02%, but preceded only 1.13% of type 2 EC cases, with an absolute risk of 0.24%, in asymptomatic women. AGC cytology and a negative HPV result preceded 1.44% of OvC, with an absolute risk of 0.28%. ConclusionsAbnormal cervical screening tests, even AGC cytology, rarely precedes and poorly predict women with EC or OvC.

Management of patients with atypical glandular cell cytology at our hospital

Management of patients with atypical glandular cell cytology at our hospital

Do High Rates of Atypical Glandular Cells Correlate With Higher Incidence of Disease in a Large Safety Net Hospital.

The aim of the study was to describe the incidence and correlates of atypical glandular cell (AGC) Pap tests in a low socioeconomic status, underserved population. Medical records of patients with AGC Pap tests at a single institution were reviewed from January 2013 to August 2019. Baseline characteristics were extracted including age, body mass index, birth control, abnormal uterine bleeding, and human papillomavirus (HPV). All colposcopy and endometrial biopsies were classified into negative/low-risk (polyps, tubular metaplasia, microglandular hyperplasia, cervical intraepithelial neoplasia 1) and high-risk (HR) lesions (cervical intraepithelial neoplasia 2/3, adenocarcinoma in situ, endometrial hyperplasia, cervical cancer, endometrial cancer). Logistic regression identified significant associations. Sixty-eight randomly selected AGC cytology slides from the cohort and 32 non-AGC slides outside the cohort were blindly reviewed by 6 pathologists. Fleiss κ interrater agreement was assessed. Seven hundred forty patients with AGC Pap tests were identified (0.8% of all Pap tests performed during this time). After excluding for incomplete data, 478 patients were included. Sixty-three patients had HR lesions (13.3%). Patients with HR lesions had increased odds of abnormal uterine bleeding (odds ratio = 4.32, p < .001) and HPV positivity (odds ratio = 10.89, p < .001) when compared with patients with low-risk lesions. The κ agreement was 0.21 for all cases and 0.18 for AGC alone. This population falls within the national averages for AGC Pap tests. There was an increased risk of HR lesions in patients with abnormal uterine bleeding and HPV positivity. The rate of HR lesions among AGC Pap tests was at the lower end of values in the literature. After blinded pathologist review, interobserver κ agreement was low for AGC Pap tests.

Cytohistological correlation in patients with atypical glandular cells on Papanicolaou test in a Chilean population.

The standard screening test for detecting cervical lesions and cancers is a Papanicolaou (Pap) smear. While squamous cell abnormalities remain the most common positive Pap test result, cytologic findings of glandular cell abnormalities have become more frequent in recent decades. The 2014 Bethesda System for reporting cervical cytology includes the classification "atypical glandular cells" (AGC). AGC have morphological abnormalities that fall outside the range of reactive changes, but are insufficient for a diagnosis of invasive adenocarcinoma. In several histologic follow-up studies, most AGC cases were found to represent a benign condition. In the current study, we evaluate the significance of AGC cytology findings by analyzing the histologic follow-up results of a large number of patients with AGC. Most patients with AGC in this study were found to have a significant lesion on follow-up (63.9%), with negative histologic results in only 36.1% of patients. Among patients with significant lesions, the most common result was low-grade squamous intraepithelial lesion (26.6%), followed by high-grade squamous intraepithelial lesion (23.2%). This provides further evidence to support the Chilean Clinical Guidelines for Cervical Cancer, which recommends diagnostic follow-up studies in all women with AGC to minimize the chance of undetected serious cervical disease.

Diagnóstico citológico de «células glandulares atípicas» como predictor de enfermedad ginecológica oncológica

ObjectivesTo evaluate the incidence of cytology reporting atypical glandular cells (AGC) in an area of Madrid, as well as to analyse the action taken on these results, the final diagnosis, and its relationship with gynaecological-oncological disease. Material and methodsA longitudinal, observational, retrospective and descriptive study was carried out on the cytology analysis performed in Area 7 of the HCSC of Madrid, between May 2006 and August 2016, was revised, selecting those reported as AGC. ResultsOf the 162,988 cytologies performed during a period of 10 years and 3 months, 40 were reported as AGC. These included 11 reported as AGC-H, 6 AGC-NOS, 22 endocervical AGC, and one endometrial AGC. Of the 75% of patients with AGC that had a disease, 25% were benign, 15% with cervical dysplasia, and 35% with a neoplasm. On analysing the results of 22 patients with endocervical AGC, one had a neoplasm, 4 an intracervical neoplasm, 9 with benign disease, and 8 negative. Of the 11 AGC-H, 10 developed neoplasms and one was negative. Among the 6 AGC-NOS, 2 neoplasms were found as cervical intraepithelial neoplasia, one benign, and one negative. Endometrial AGC cytology showed an endometrial adenocarcinoma. ConclusionThe incidence of cytology in our area with AGC result is very low (0.025%). The probability of having an underlying cytological alteration is high, which in turn should lead to an exhaustive study of these patients according to the recommendations of the scientific societies, since a non-negligible percentage can translate into the existence of severe malignant diseases, not only cervical, but also endometrial or ovarian.

Significance of high-risk HPV detection in women with atypical glandular cells on Pap testing: Analysis of 1857 cases from an academic institution.

The role of high-risk human papillomavirus (hrHPV) testing in women with various types of atypical glandular cells (AGC) on Papanicolaou (Pap) test is undetermined. Herein, the authors retrospectively searched their pathology database for cases of AGC with concurrent hrHPV testing and histological follow-up results within 1 year between January 2008 and December 2013. Among 3709 AGC cases occurring during the study period, 2287 had concurrent Hybrid Capture 2 HPV testing results. The overall rate of hrHPV positivity (hrHPV+) was 27.7%. Of these 2287 cases, 1857 cases (81.2%) had histological follow-up results within 1 year, including 529 hrHPV + cases and 1328 hrHPV-negative (hrHPV-) cases. Among the hrHPV + cases, 16.8% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 5.7% had cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 1.1% had an endometrial carcinoma. Among the hrHPV- cases, 0.6% had CIN2/3, 0.2% had AIS/ADC, and 3.8% had an endometrial carcinoma. The rate of high-grade cervical lesions (CIN2/3, AIS, or ADC) was significantly higher in women who were hrHPV + compared with hrHPV- women for all age groups. Endometrial carcinoma was most commonly present in women aged ≥50 years. To the authors' knowledge, the current study is the largest follow-up study published to date regarding women with AGC cytology and HPV testing. The study data indicate that hrHPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with AGC, but has no significant value in evaluating the risk of endometrial carcinoma. The combination of cytology, hrHPV testing, and patient age can significantly aid in the appropriate management of these individuals. Cancer Cytopathol 2017;125:205-211. © 2016 American Cancer Society.

High-grade Cervical Histopathology in Women with Atypical Glandular Cell Cytology.

This study was undertaken to evaluate the prevalence of underlying significant lesions among women referred for colposcopy after atypical glandular cell (AGC) smears and the associated risks. The present study reviewed data from women with AGC smears undergoing colposcopy at the Colposcopy Clinic, Faculty of Medicine, Khon Kaen University, Thailand between January 2001 to December 2014. Significant lesions included cervical intraepithelial neoplasia grade 2-3, adenocarcinoma in situ, endometrial hyperplasia, and cancer. During the study period, 170 women with AGC cytology were reviewed. The mean age was 45.7 years. Thirty-eight women (22.4%) were postmenopausal. Eighteen smears (10.6%) were further subclassified as AGC-favor neoplasia (AGC-FN). In total, significant lesions were noted in 27 women (15.9%; 95%CI, 7.8%-18.3%). Thirteen women (7.6%, 95%CI, 4.1%-12.7%) were found to have cervical cancer or endometrial cancer. Two variables were independently associated with an increased risk of significant histopathology results: level of educational attainment (secondary level or lower versus bachelor degree or higher) and types of AGC (AGC versus AGC- FN). Women who had low level of education and those with AGC-FN were at the higher risk of significant lesions (OR, 3.16; 95%CI 1.10-9.11 and OR, 4.62; 95%CI, 1.54-13.85, respectively). In conclusion, the rate of significant lesions among women referred for colposcopy after AGC smears is considerably high. Low education and smear subtypes appear independently associated with a higher risk of significant lesions.

Preoperative Cervical Cytology and E-Cadherin Expression in Endometrial Cancer

Objective: It is reported that cervical cytology is a significant factor related to stage, tumor grade, nodal metastasis, recurrence and survival rate in endometrial cancer. Moreover, reduced expression of the cell adhesion molecule E-cadherin is associated with higher tumor grade and metastasis in endometrial cancer. The objective of this study is to evaluate the relationship between the results of cytological assessment of glandular cells in cervical cytology before surgery, prognostic factors, and E-cadherin expression in endometrial cancer. Methods: Between 2004 and 2011, 263 patients with endometrial cancer at all stages were treated with hysterectomy. We reviewed preoperative cervical smears and assigned each to one of three categories: (1) Negative, (2) Atypical glandular cells (AGC), and (3) Adenocarcinoma (AC). The relationship of these cytology, prognostic factors, and E-cadherin expression was evaluated. Results: Statistical significance in overall survival was shown for preoperative cervical cytology, age, surgical stage, histological type, tumor grade, myometrial invasion, cervical involvement, lymph node metastasis except peritoneal cytology. Patients with AC cytology were more likely than those with normal cervical cytology to have a higher International Federation of Gynecology and Obstetrics (FIGO) stage, poorer histopathology, higher tumor grade, deeper myometrial invasion, higher incidence of cervical involvement, and higher prevalence of lymph node metastasis. In addition, AC and AGC cytology appeared to be associated with a poorer prognosis and to have lower E-cadherin expression than negative cytology. Conclusions: Cervical cytology may be a guide to prognosis in endometrial cancer, and E-cadherin expression may correlate with appearances of abnormal endometrial cells.

Clinical Implication of a Typical Glandular Cells; a Five Years Experience of a Single Institution in Portugal

Objective: The study aimed to evaluate the clinical significance of atypical glandular cells (AGC) in cervical cytological reports and its correspondent subtypes. Material and methods: Retrospective study of AGC cervical cytological diagnoses, from January 2009 to December 2013, at a tertiary centre. A global analysis of AGC and its correspondent subtypes was performed, according to age, onset of sexual life, Human Papilloma Virus deoxyribonucleic acid (HPV-DNA) status, diagnostic procedures and follow-up histological outcomes. Results: Cervical AGC cytology had a prevalence of 0.3% among women with an average age of 46.8 ± 14.5 years. The distribution showed 81% of AGC-not otherwise specified (AGC-NOS) and 10.7% of AGC-favor neoplastic (AGC-FN). AGC-NOS had a higher prevalence of benign pathology. AGC-FN showed an association to in situ adenocarcinoma, a superior incidence of endometrial carcinoma and a tendency towards a higher prevalence of squamous cervical intraepithelial neoplasia. Glandular and squamous coexisting cytological abnormalities accounted for 8.3% and were mostly associated with squamous lesion. HPV-DNA testing demonstrated a sensitivity of 50% with a specificity of 100% for detection of cervical lesions. Discussion: Close follow-up of AGC is required once pre-malignancy and malignant disease was identified in 20.8% of patients. A precise study of cervix and endometrium assumes equal importance, significant pathology was found in both locations.

Interpretation and management of AGC cytology

Background Cervical cytology has continually evolved. Nowadays, the category of atypical glandular cells (AGC) is less frequent than atypical squamous cells (ASC), associating poorlyreproducible inter-observer interpretation. Cellular characters sometimes surpass benign reparatory processes or associate high-grade squamous precursor lesions, glandular neoplasia, including cervical adenocarcinoma, endometrial neoplasm and even extrauterine adenocarcinomas. Therefore, AGC needs special attention and aggressive diagnostic procedures. Nevertheless, the most common viral infection of the reproductive tract, the human-papillomavirus (HPV) infection, shouldn’t be underestimated, as about 30% of AGC cases are HPV-positive. The presence of HPV in AGC patients identifies a group at higher-risk for developing cervical neoplasia. Studies show that 70% of AGCHPV-negative patients have no evidence of cervical cancer, and 76% of AGC-HPV-positive results may present glandular or squamous neoplasia.

Factors predicting pathologic significance among women with atypical glandular cells on liquid-based cytology

ObjectiveTo determine incidence, originating organ, and factors predicting significant histopathology (premalignant and malignant lesions) among women with atypical glandular cells (AGCs) on liquid-based cytology (LBC). MethodsIn a retrospective study at Siriraj Hospital, Bangkok, Thailand, clinical and histologic data were reviewed for women with AGCs who underwent appropriate examinations from January 2007 to December 2010. ResultsThere were 284 women with AGC cytology (mean age, 51.2years). The incidence of significant pathology and invasive cancer was 43.3% and 34.5%, respectively. The most common malignant organ was the uterus (64/123, 52%). Predictors of serious pathology were AGC favor neoplasia (AGC-FN) endocervical (odds ratio [OR], 5.64; 95% confidence interval [CI], 1.62–19.57), AGC-FN endometrial (OR, 4.11; 95% CI, 1.27–13.32), AGC-FN glandular (OR, 8.23; 95% CI, 2.02–33.49) subtypes, and bleeding (OR, 2.88; 95% CI, 1.47–5.65). Combining patient age and AGC subtype, there were no serious cervical lesions among women aged 50years or younger with AGC-FN glandular subtype, or serious non-cervical neoplasia among women aged 50years or younger with AGC not otherwise specified (AGC-NOS) or AGC-FN endocervical subtypes. ConclusionAGC subcategories defined from LBC, alone or combined with patient age, might be predictors of significant histopathology, cancer incidence, and originating organ.

Adherence to practice guidelines for atypical glandular cells on cervical cytology

Atypical glandular cells (AGC) on cervical cytology are high-risk, requiring an extensive evaluation. Compliance with practice guidelines for AGC, however, has been low. Some AGC cytology reports contain cytopathologist recommendations for evaluation. This study determines whether evaluation rates for AGC have improved over time, and whether cytopathologists' recommendations correlate with the types of evaluation women receive. Evaluation rates from 284 women with AGC (2004-2007) were compared with findings from 1998-2001. Rates of evaluations were compared based on cytology report recommendations. A total of 76.1% of the AGC cases had histologic sampling, and 58.8% had a comprehensive evaluation. These rates are higher than those from 1998-2001 (63.5% and 35.8%, respectively; P<.01). Rates of evaluations of women with AGC "favor neoplasia" did not increase between the 2 time periods. Between 2004-2005 and 2006-2007, rates of comprehensive initial evaluations and endometrial sampling in women ≥35 years of age did not increase. Of the AGC reports that did contain cytopathologist recommendations, 28% were consistent with practice guidelines, 26% recommended an incomplete histologic evaluation, and 46% recommended repeat cytology. Women whose AGC report recommended a comprehensive evaluation or any histologic evaluation were more likely to have a comprehensive work-up (79%) than those whose reports did not contain recommendations (55%, P <0.01) or recommended repeat cytology (51%, P<0.02). Adherence to practice guidelines for the evaluation of women with AGC has improved but continues to be suboptimal. Our findings suggest that continuing education and including practice guidelines on AGC cytology reports may improve compliance.

Differences in Cervical Cytologic and Histologic Findings Between Women Using Depot-Medroxyprogesterone Acetate and Oral Contraceptives

This study aimed to compare cervical cytologic and histologic findings between women using depot-medroxyprogesterone acetate (DMPA) and oral contraceptives (OCs) referred for colposcopy and to determine whether there were differences in the occurrence of false-positive cytologic finding between the 2 contraceptive groups. Retrospective cohort of 1,569 premenopausal women using either DMPA or OC who were evaluated for abnormal cervical cytologic findings. Cytologic and histologic data were collected in conjunction with routine gynecologic examinations or follow-up colposcopic evaluations. χ2 tests were used to determine differences in cervical cytologic and histologic findings and the proportion of false-positive results across contraceptive groups. Nominal logistic regression was used to evaluate the association between contraceptive use, cervical, and histologic abnormalities while controlling or age and smoking status. The mean age of all participants was 23.5 years, with no significant difference between OC (n = 1194) and DMPA (n = 375) users. Although there were no differences in the proportion of false-positive cytologic results (21.8% overall), DMPA users were more likely to smoke (p < .001), have atypical glandular cell (AGC) on referral cytology (p < .001), and have histologic confirmation of cervical intraepithelial neoplasia 2, 3 (p = .004). Users of DMPA remained more likely to have AGC cytology after considering smoking status; however, cervical intraepithelial neoplasia 2, 3 was found to be associated with smoking status and not use of DMPA. We found no difference in the proportion of false-positive cytologic results between DMPA and OC users referred for evaluation of abnormal cytology. Users of DMPA were more likely to have AGC, which necessitates a more comprehensive evaluation.

The Age-Specific Relationships of Abnormal Cytology and Human Papillomavirus DNA Results to the Risk of Cervical Precancer and Cancer

To estimate the relationship of human papillomavirus (HPV) detection and abnormal cytology with histologic diagnoses of cervical precancer and cancer. From 2003 to 2008 we examined the HPV, cytology, and diagnostic results from almost one million cervical cancer screenings done on women aged 30 and older who were members in Kaiser Permanente Northern California, a large health maintenance organization that introduced cotesting in 2003. Women were screened using conventional Pap tests and a DNA test for a pool of 13 high-risk HPV genotypes. Women with HPV-positive atypical squamous cells of undetermined significance and other abnormal cervical cytology, independent of their HPV results, routinely underwent colposcopy. Results were stratified by 5-year age groups from 30 to 64. High-grade squamous intraepithelial lesions (HSIL), atypical squamous cells, cannot exclude HSIL (ASC-H), and atypical glandular cells were more strongly associated with cervical intraepithelial neoplasia grade 3 while low-grade squamous intraepithelial lesions (LSIL) and HPV-positive atypical squamous cells of undetermined significance were more strongly associated with cervical intraepithelial neoplasia grade 2 (CIN2). Cervical cancer was most commonly found in women with HSIL and atypical glandular cells cytology. Human papillomavirus-negative women with ASC-H cytology were at a reduced but significant risk of CIN2 or more severe (CIN2+) (10.6%) compared with HPV-positive women with ASC-H cytology. Human papillomavirus-negative women with LSIL were at a 4.0% risk of CIN2+, and among women 50 and older, at a 0.5% risk of CIN2+ with no cancers were diagnosed. Human papillomavirus testing may be useful for triage for colposcopic referral for LSIL cytology in older women but not for ASC-H cytology at any age. II.

Relationship of Atypical Glandular Cell Cytology, Age, and Human Papillomavirus Detection to Cervical and Endometrial Cancer Risks

To quantify the age-specific and reproductive organ-specific cancer risk after an atypical glandular cell (AGC) cytologic interpretation in large clinic-based sample in which routine high-risk human papillomavirus (HPV) testing is conducted. : To estimate the absolute risk of cervical precancer, cervical cancer, and endometrial cancer in women with AGC cytology, we conducted a cross-sectional study of women with AGC cytology (n=1,422) in a large health maintenance organization that introduced high-risk HPV DNA testing into cervical cancer screening in 2003. Risks and binomial exact 95% confidence intervals (CIs) of cervical intraepithelial neoplasia grade 2 or more severe (CIN 2 or worse) and endometrial cancer were calculated. A total of 238 women with AGC cytology (16.7%, 95% CI 14.8-18.8%) were diagnosed with CIN 2 or worse, endometrial cancer, or other cancers. Among women aged 50 years or older, 420 high-risk HPV-negative women were at a 10.5% (95% CI 7.7-13.8%) risk of endometrial cancer, and 77 high-risk HPV-positive women were at a 10.4% (95% CI 4.6-19.4%) risk of cervical cancer and 0% (95% CI 0.0-4.7%) risk of endometrial cancer. High-risk HPV testing may distinguish between risk of endometrial cancer and cervical cancer in women with AGC cervical cytology, particularly in women aged 50 years or older. III.