Anal cancer screening among women with HIV: provider experiences and system-level challenges.

Women living with HIV (WLWH) are at increased risk of anal cancer compared to women without HIV, often due to persistent human papillomavirus (HPV) infections. This paper describes current practices and challenges conducting anal cancer screening for WLWH at an urban integrated safety-net system and a non-profit community-based HIV clinic. We conducted 25 semi-structured interviews with clinical and administrative stakeholders to assess knowledge, clinic practices and procedures, and experiences with anal cancer screening. Interview transcripts and fieldnotes were thematically analyzed using an iterative deductive and inductive coding scheme. Findings were organized by the Consolidated Framework for Implementation Research (CFIR) domains and constructs. Provider-level barriers to conducting anal cancer screening included limited knowledge of guidelines. System-level barriers included: structural characteristics such as lack of coordination between clinics to discern provider roles and responsibilities; and limitations in available resources such as configuration of electronic health records and infrastructure to manage referrals of abnormal anal Pap results. We conclude that anal cancer screening and follow-up for WLWH requires organization and coordination between multiple care teams, updated clinical information systems to facilitate communication and support anal Pap ordering and result documentation, and infrastructure that includes policies and protocols for management of abnormal results.Trial registration: ClinicalTrials.gov identifier: NCT02135419.

The first comprehensive report on Indigenous Australian women's inequalities in cervical screening: A retrospective registry cohort study in Queensland, Australia (2000-2011).

BACKGROUND: The Australian National Cervical Screening Program, introduced more than 20 years ago, does not record the Indigenous status of screening participants. This article reports the first population-based estimates of participation in cervical screening for Indigenous and non-Indigenous Australian women. METHODS: This was a retrospective, population-based study of 1,334,795 female Queensland residents, aged 20 to 69 years, who participated in cervical screening from 2000 to 2011; 26,829 were identified as Indigenous through linkage to hospitalization records. Participation rates were calculated as the number of women screened divided by the average estimated resident population, with adjustments made for hysterectomies, for each 2-, 3-, and 5-year screening period. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), which were adjusted for age group, place of residence, and socioeconomic disadvantage. RESULTS: In 2010-2011, the 2-year participation rate was 55.7% (95% CI, 55.6%-55.9%) for non-Indigenous women and 33.5% (95% CI, 32.9%-34.1%) for Indigenous women; this represented a decrease from 2000-2001 (57.7% [95% CI, 57.6%-57.9%] and 35.3% [95% CI, 34.5%-36.1%], respectively). The difference between Indigenous and non-Indigenous women was greatest for those aged 45 to 49 years. The 3- and 5-year participation rates were higher within both groups, and the absolute differences between the 2 groups were larger. Significant interactions between the Indigenous status and the place of residence and socioeconomic disadvantage highlight that the Indigenous/non-Indigenous differential was evident in all places of residence except for very remote areas (OR, 0.99; 95% CI, 0.95-1.02) and was greatest in the most affluent areas (OR, 0.26; 95% CI, 0.24-0.27). CONCLUSIONS: Indigenous Australian women participate less than non-Indigenous women, and this gap has not closed. These results provide important benchmarks for the new Australian cervical screening program commencing in 2017, which will provide opportunities to reduce inequities for Indigenous women and address longstanding data deficiencies in the collection of the Indigenous status. Cancer 2016;122:1560-9. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Atypical glandular cells in Pap tests: cytology-histology correlation and risk assessment with human papillopmavirus (HPV) testing.

INTRODUCTION: Atypical glandular cells (AGC) represent less than 1% of Pap test cases and include a variety of lesions in both the cervix and endometrium. The study aimed to investigate the cytology-histology correlation in AGC patients and to evaluate the clinical utility of hrHPV testing in this diagnostic context. MATERIALS AND METHODS: We identified 491 atypical glandular cells (AGC) cases in our quality analysis (QA) database of 336,064 Pap tests interpreted between March 1, 2013 and July 12, 2016. Of these, 251 cases had follow-up biopsies with hrHPV tests in 148 cases. RESULTS: The most common histologic diagnosis associated with AGC was normal/benign or low-grade lesions, comprising 55% of cervical biopsies and 24% of endometrial biopsies. High-grade lesions were identified in 21% of follow-up biopsies. In patients with AGC cytology, a positive hrHPV test significantly increased the likelihood of cervical HSIL or above lesions on biopsy by 26.4 times (OR = 26.4, 95% CI: 5.8-119.4, P < 0.0001). A positive genotyping result for HPV 16 dramatically increased the likelihood of cervical HSIL or above lesions on biopsy (OR = 84, 95% CI: 12.0-590.5, P < 0.0001). The HPV test had a negative predictive value of 97% (CI: 85%-100%). CONCLUSIONS: Our study confirms that AGC is a significant diagnosis with an overall risk for high-grade cervical or endometrial lesions as high as 21%. hrHPV testing with genotyping is an effective tool for identifying high-risk individuals within the AGC population, with excellent positive and negative predictive values. This approach is valuable for clinical risk stratification and differential diagnosis in patients with AGC cytology.

Genotype profile of HPV in ASC-H cytology and histologic follow-up-prevalence, distribution, and risk: A retrospective study of 1414 cases.

BACKGROUND: A cytologic diagnosis of atypical squamous cells, cannot exclude high-grade squamous lesion (ASC-H) poses a disproportionately high risk of cervical cancer development. The objective of this study was to analyze type-specific risks by mapping human papillomavirus (HPV) genotypes in ASC-H cytology. METHODS: In total, 1,048,581 Papanicolaou tests that had ASC-H cytology were retrieved. Concurrent HPV genotyping using proprietary multiplex real-time (MRT) and polymerase chain reaction (PCR) HPV tests and histologic follow-up findings were analyzed. RESULTS: Among 1678 patients who had ASC-H findings (0.16%), 1414 (84.3%) underwent concurrent HPV genotyping (MRT, 857; HPV PCR test, 557). The overall high-risk HPV (hrHPV)-positive rate was 84.4%. Of the 857 MRT cases, 63.9% were infected with a single hrHPV, and 24.4% had multiple genotypes. The most prevalent HPV types were HPV16/52/58/33/31. Lesions that were identified as cervical intraepithelial neoplasia 2 or worse (CIN2+) were detected in 498 of 906 cases (55.0%), including 81 cervical carcinomas (8.9%). The risk of CIN2+ for the composite group of HPV16/52/58/33/31-positive cases was 62.7%, representing 90.7% (264 of 291) of total CIN2+ lesions in ASC-H/hrHPV-positive cases by MRT. CIN2+ lesions were detected in 108 of 142 (76.1%) HPV16-positive and/or HPV18-positive women by the PCR the HPV test. Among 128 hrHPV-negative ASC-H cases by both methods, CIN2+ lesions were identified in 21 of 128 (16.4%), including five cervical carcinomas (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value for patients in the composite group with HPV16/52/58/33/31 were 88.0%, 40.8%, 62.7%, and 75.0%, respectively. CONCLUSIONS: Papanicolaou tests classified as ASC-H are associated with a high CIN2+ rate and warrant colposcopy, regardless of HPV status. The extent to which the risk-stratification provided by comprehensive HPV genotyping can inform the management of ASC-H cytology remains to be explored.

Understanding the effect of new U.S. cervical cancer screening guidelines and modalities on patients' comprehension and reporting of their cervical cancer screening behavior.

With recent shifts in guideline-recommended cervical cancer screening in the U.S., it is important to accurately measure screening behavior. Previous studies have indicated the U.S. National Health Interview Survey (NHIS), a resource for measuring self-reported screening adherence, has lower validity among non-White racial/ethnic groups and non-English speakers. Further, measuring diverse population groups' comprehension of items and attitudes toward HPV self-sampling merits investigation as it is a modality likely to be recommended in the U.S. soon. This study cognitively tested NHIS items assessing recency of and reasons for receiving cervical cancer screening and attitudes toward HPV self-sampling. We conducted cognitive interviews between April 2021 - April 2022 in English and Spanish with individuals screened in the past two years by either a medical center in metropolitan Seattle, Washington or a safety-net healthcare system in Dallas, Texas. Interviews probed understanding of reasons for screening, experiences with abnormal results, and interest in HPV self-sampling. We completed 32 interviews in Seattle and 42 interviews in Dallas. A majority of participants were unaware that two different tests for cervical cancer screening exist (Pap and HPV). Many did not know which type(s) of test they received. Dallas participants had more limited and inaccurate knowledge of HPV compared to Seattle participants, and fewer responded favorably toward HPV self-sampling (32% vs. 55%). To improve comprehension and accurate reporting of cervical cancer screening, we suggest specific refinements to currently used survey questions. Attitudes toward self-sampling should be explored further as differences may exist by region and/or sociodemographic factors.

Role of High-Risk HPV Testing in Papanicolaou Tests With Atypical Glandular Cells With and Without Concurrent Squamous Cell Abnormalities.

OBJECTIVES: Data on Papanicolaou (Pap) tests with atypical glandular cells (AGCs) with concurrent squamous cell abnormalities (AGC + Sq) are limited. We evaluated histologic outcomes and the role of high-risk human papillomavirus (HR-HPV) testing in this setting compared with AGCs without concurrent squamous cell abnormalities (AGC-alone). METHODS: This study used a retrospective cohort of patients with Pap test diagnoses of AGC + Sq and AGC-alone between October 2013 and August 2021. RESULTS: We included 287 Pap tests from 278 patients. The HR-HPV test was positive in 55% of AGC + Sq cases and 14% of AGC-alone cases (P < .0001). Most AGC + Sq cases displayed squamous lesions (41.5%) or were benign (41.5%) on histology, whereas AGC-alone cases were predominantly benign (72%) or extracervical neoplasms (18%). AGC + Sq cases showed higher rates of significant histologic lesions (P = .0001), which were associated with positive HR-HPV status (P = .0012). In AGC-alone cases, HR-HPV status was associated with significant histology only in patients 50 years of age or younger. In both groups, 20% or more of HR-HPV-negative patients harbored significant lesions. CONCLUSIONS: AGC + Sq represents a distinct group of patients. HR-HPV testing and patient age provide useful information in the evaluation of AGC, but triage based on HR-HPV testing is not recommended because of the potential for missing significant lesions.

Factors Affecting the Histopathological Outcomes of Atypical Glandular Cells on Pap Test.

BACKGROUND: Glandular cell abnormalities may indicate the presence of pre-malignant or malignant lesions. AIM: This study aimed to investigate the relationship between atypical glandular cells (AGC) and patients' demographics, histopathological outcomes, Human Papillomavirus (HPV) test results. MATERIAL AND METHODS: Between January 2015 and December 2019, women with AGC on Pap tests were retrieved from the hospital electronic database. The patients with AGC on cervicovaginal smears who underwent further pathological, laboratory, and imaging diagnostic testing and who were followed up at least 1-year were included in the study, while those who had a history of cervical dysplasia or cancer, lost during follow-up, or had missing data were excluded. RESULTS: Of 85,692 Pap smears, 114 (0.13%) were diagnosed with AGC, of those 88 cases were eligible for final analysis. Gynecological malignancies were detected in 13 (14.8%) patients; including 6 (6.8%) endometrioid endometrial cancers, 3 (3.4%) non-endometrioid endometrial cancers, 2 (2.3%) cervical adenocarcinomas, 1 (1.1%) cervical squamous cell carcinoma, and 1 (1.1%) high-grade tubal serous cancer. Multivariate analysis revealed that presence of concomitant abnormal squamous lesion (P = 0.002), being 50 years and older (P = 0.028), HPV positivity (P < 0.001), and menopause (P = 0.023) were risk factors for significant pathology. CONCLUSION: The diagnosis of AGC may be related to the preneoplastic/neoplastic processes. A further comprehensive histopathological examination is required in women with AGC, aged 50 years and older, postmenopausal, HPV-positivity and concomitant squamous cell abnormality Clinicians should consider ovarian pathologies when there is no pathological finding on endometrial or cervical histopathological examination.

Aptima HPV messenger RNA testing and histopathologic follow-up in women with HSIL cytology: A study emphasizing additional review of HPV-negative cases.

BACKGROUND: High-risk human papillomavirus (hrHPV) messenger RNA (mRNA) testing, the Food and Drug Administration-approved testing platform since 2013, has been increasing as a cervical screening alternative to hrHPV DNA testing methods. This study reports the largest routine clinical follow-up study reported to date of hrHPV mRNA cotesting and histopathologic follow-up results for women with high-grade squamous intraepithelial lesion (HSIL) cytology results. METHODS: HSIL Papanicolaou test results for women cotested with Aptima hrHPV mRNA testing between June 2015 and November 2020 were analyzed along with recorded histopathologic follow-up results within 6 months of screening. RESULTS: Aptima hrHPV mRNA-positive results were reported for 95.2% of the cotested HSIL cytology cases (905 of 951). Histopathologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed on follow-up in 538 of 701 hrHPV mRNA-positive cases (76.8%) and in 15 of 36 hrHPV mRNA-negative cases (41.7%). Additional reviews of the hrHPV mRNA-negative HSIL cases showed variable interpretations, and confirmatory blinded-review interpretations of HSIL or atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion were more likely in cases with histopathologic CIN2+ (77.5% [93 of 120]) than those with cervical intraepithelial neoplasia grade 1 or negative findings (63.1% [101 of 160]; P < .01). CONCLUSIONS: This large routine-clinical-practice study confirms the previously reported high sensitivity of hrHPV mRNA testing for the detection of high-grade cervical dysplasia and cervical cancers. The blinded-review findings indicate that additional cytology review may be helpful for confirming an interpretation of HSIL in daily practice, especially for hrHPV-negative HSIL cases.

High-Risk Human Papillomavirus Testing, Genotyping, and Histopathologic Follow-up in Women With Abnormal Glandular Cells on Papanicolaou Tests.

OBJECTIVES: This study examined the association of high-risk human papillomavirus (hrHPV) status and HPV genotype with histopathologic follow-ups in women with an atypical glandular cell (AGC) interpretation. METHODS: Cases with AGC interpretation on a Papanicolaou (Pap) test were retrieved along with hrHPV testing, genotyping, and histologic follow-up results if available. RESULTS: A total of 561 AGC cases were identified, with histologic follow-up available for 471 cases (84%). The follow-up diagnoses included benign or reactive changes (60% of cases), low-grade cervical intraepithelial neoplasia (18%), high-grade cervical intraepithelial neoplasia (CIN2-3; 7%), cervical carcinoma (5%), and other malignancies (10%). Tests for hrHPV were positive in 128 of 426 (30%) cases, including HPV16 (30%), HPV18 (14%) and other HPV subtypes (56%). A positive hrHPV result significantly increased the risk of developing CIN2-3 or cervical carcinoma (odds ratio, 24.6; 95% CI, 9.9-58.9) and HPV16 or HPV18 further increased the risk (odds ratio, 49.5; 95% CI, 17.7-123.7). CONCLUSIONS: Our data demonstrate that in women with an AGC Pap interpretation, a positive hrHPV result, especially type 16 or 18, is associated with an increased risk of developing cervical CIN2-3 or higher lesions, suggesting potential implications of hrHPV testing for the management of patients with an AGC result on a Pap test.

Queer in the Heartland: Cancer Risks, Screenings, and Diagnoses among Sexual and Gender Minorities in Iowa.

Little is known about the cancer experiences of sexual and gender minority (SGM) persons in Midwestern areas. In response, a statewide survey of 567 SGM adults in Iowa, a largely rural Midwestern state, assessed cancer prevalence, screening tests, and related risk factors. Skin cancer accounted for nearly half of reported cancers. Individuals assigned female sex at birth reported high levels of lifetime mammograms and Papanicolaou (Pap) tests. In contrast, there were almost no colorectal cancer screenings reported among older (age 50+) respondents, regardless of gender identity or sexual orientation. Current tobacco use was modest overall, and cisgender women were more likely to report heavy drinking than cisgender men. Cisgender men age 40 and younger were less likely to have any human papillomavirus vaccination than cisgender women. The survey identified both strengths to leverage and deficits to address, which may inform future cancer prevention efforts in Iowa and other Midwestern states.

Anal cytological lesions and HPV infection in individuals at increased risk for anal cancer.

BACKGROUND: Anal cytology may be useful for evaluating lesions associated with human papillomavirus (HPV) in individuals at increased risk for anal cancer. METHODS: Liquid-based cytology was used to assess anal cytological lesions among human immunodeficiency virus (HIV)-infected and HIV-uninfected men who have sex with men (MSM). The Linear Array HPV genotyping test was used for HPV detection. RESULTS: This cross-sectional study included 1021 MSM, of whom 388 were HIV-infected (38.0%). Anal cytological lesions (atypical squamous cells of undetermined significance or more severe [ASCUS+]) were observed in 32.5% and 53.2% of the HIV-uninfected and HIV-infected individuals, respectively (P < .0001). The highest ASCUS + prevalence was observed among ≥45-year-old HIV-uninfected MSM (37.3%) and 25-to 29-year-old HIV-infected MSM (66.7%). High-grade squamous intraepithelial lesions (HSILs) peaked in ≥ 45-year-old HIV-uninfected subjects and 35- to 39-year-old HIV-infected subjects. Individuals with anal infections with high-risk (HR) HPV types were 3 to 4 times more likely to have an ASCUS + report. An HPV-16 and/or HPV-18 infection increased the odds of HSIL or more severe cytology (HSIL+) for HIV-infected MSM almost 4 times. MSM concurrently infected with HR and low-risk HPVs were significantly more likely to have low-grade squamous intraepithelial lesions or more severe cytology (LSIL+) than those infected with only HR types. No significant associations were found between cytological abnormalities and the HIV load and nadir and current CD4 + counts. CONCLUSIONS: The prevalence of anal cytological lesions is high in MSM, even in HIV-infected individuals treated with combined antiretroviral therapy. In these subjects, HSILs occur more frequently and at a younger age in comparison with HIV-uninfected counterparts. Specific diagnostic procedures should be implemented to manage individuals at increased risk for anal cancer with an abnormal anal Papanicolaou test. Cancer Cytopathol 2018. © 2018 American Cancer Society.

Knowledge of the HPV status biases cytotechnologists' interpretation of Pap tests originally diagnosed as negative for intraepithelial lesion or malignancy.

BACKGROUND: Because of cervical cancer screening recommendations and forthcoming first-line human papillomavirus (HPV) screening, many Papanicolaou (Pap) tests will be performed in patients with known concurrent HPV results. This study was designed to evaluate whether knowledge of the HPV status affects cytotechnologists' interpretation of Pap tests. METHODS: A retrospective search of cervical screening Pap tests with known concurrent HPV results provided 250 ThinPrep Pap tests, which were chosen to reflect an atypical rate similar to the rate of the Cleveland Clinic's normal practice. Fifty percent of negative for intraepithelial lesion or malignancy (NILM) and atypical squamous cells of undetermined significance (ASCUS) cases were from patients with positive HPV results. Slides were re-evaluated twice by 8 cytotechnologists blinded to the diagnosis and study purpose. The HPV status was provided for 50% of the cases in the first phase; after a washout period, knowledge of the HPV status for each case was reversed in the second phase. Follow-up information was collected from the medical record. RESULTS: In both phases, there was a significant bias for HPV-positive NILM cases to be upgraded to ASCUS or worse when the HPV-positive status was provided (P < .001). When the HPV status was withheld, there was no difference in upgrading NILM cases (phase 1, P = .69; phase 2, P = .066). A combined analysis showed a significant bias in referral to the pathologist when the HPV-positive status was provided rather than withheld (P < .001). Follow-up data revealed no significant effect of bias when the HPV-positive status was provided between patient groups with benign, low-grade, or high-grade follow-up. CONCLUSIONS: A known HPV-positive status biases cytotechnologists' interpretation of Pap tests, and this results in a higher rate of upgrading to ASCUS or worse; however, it does not improve sensitivity for disease detection. Cancer Cytopathol 2017;125:60-69. © 2016 American Cancer Society.

Three-year risk of high-grade CIN for women aged 30 years or older who undergo baseline Pap cytology and HPV co-screening.

BACKGROUND: Papanicolaou (Pap) cytology and high-risk human papillomavirus (HPV) DNA cotesting for women aged ≥30 years are recommended for the prevention of cervical cancer. The objective of the current study was to evaluate the efficacy of this cotesting for predicting the risk of high-grade cervical intraepithelial neoplasia 3 (CIN3) during a 3-year follow-up period. METHODS: A retrospective database search identified women aged ≥30 years who had baseline HPV and Pap cytology cotesting results in 2007 or 2008 and for whom 3-year follow-up results were available. The cumulative 3-year risks of developing CIN-3 were calculated. RESULTS: The 3-year follow-up data after baseline Pap/HPV cotesting were available for 1986 women (mean age, 53 years). Of the 1668 women who had a baseline Pap-negative (Pap-)/HPV- cotesting result, 1561 (93.6%) had a follow-up Pap cytology result that was negative for intraepithelial lesions or malignancy. Of the 1530 women who had follow-up Pap/HPV cotesting, 1504 (98.3%) had a Pap-/HPV- result. The 3-year cumulative risk of developing CIN-3 was found to be highest for women with a baseline Pap-positive (Pap+)/HPV+ cotesting result (12.5%); the risk of CIN-3 was lower in those with a Pap-/HPV+ result (1.5%; P = .0032) or a Pap-/HPV- result (0.06%; P<.0001). The 3-year cumulative risk of CIN-3 was found to be significantly greater for women with an HPV+ result (4.8%) compared with those with an HPV- result (0.06%; P<.0001). CONCLUSIONS: Pap cytology and HPV cotesting are valuable for stratifying CIN-3 risk. Pap cytology and HPV co-screening at a 3-year screening interval appears to carry a low risk of CIN-3 for women who have a baseline Pap-/HPV- cotesting result. Cancer Cytopathol 2017;125:644-51. © 2017 American Cancer Society.

Performance of Aptima and Cobas HPV testing platforms in detecting high-grade cervical dysplasia and cancer.

BACKGROUND: Human papillomavirus (HPV) tests and genotyping have been used in clinical risk assessment. The purpose of this study was to analyze the performance of 2 common HPV testing platforms in detecting high-grade cervical lesions (high-grade squamous intraepithelial lesion [HSIL] or worse [≥HSIL]). METHODS: Between January 1 and December 31, 2015, 2041 Papanicolaou (Pap) tests with biopsy confirmation were analyzed along with HPV tests performed on Cobas or Aptima platforms. A biopsy diagnosis of grade 2 cervical intraepithelial neoplasia was confirmed with p16/Ki-67 immunohistochemistry. RESULTS: In total, 1866 and 175 Pap cases were tested on Cobas and Aptima platforms, respectively. Both platforms were highly sensitive (97% for both) for biopsy-confirmed ≥HSIL. Cobas HPV testing had higher positive rates for the diagnosis of benign lesions (84% vs 51%) and low-grade squamous intraepithelial lesions (89% vs 63%) on biopsy compared with Aptima. Aptima testing had significantly higher specificity for ≥HSIL than Cobas (41% vs 13%; P < .0001). Overall, performance of the Aptima platform was superior to that of the Cobas platform in detecting biopsy-confirmed ≥HSIL, resulting from its significantly higher positive predictive value (25% vs 16%; P < .03) and overall accuracy (50% vs 26%; P < .0001). CONCLUSIONS: Although both the Cobas and Aptima platforms offer highly sensitive tests for high-grade cervical lesions, Aptima HPV testing demonstrated significantly higher specificity and positive predictive value than Cobas testing for biopsy-confirmed ≥HSIL. The considerable difference may be related to the significant increase in E6/E7 expression after HPV DNA integration. The significantly higher specificity and overall accuracy of Aptima testing for ≥HSIL, resulting in the identification of high-risk populations that require immediate treatment and close follow-up, may prove useful in clinical risk stratification. Cancer Cytopathol 2017;125:652-7. © 2017 American Cancer Society.

Clinical significance of atypical glandular cells in Pap tests: An analysis of more than 3000 cases at a large academic women's center.

BACKGROUND: The interpretation of atypical glandular cells (AGC) in Papanicolaou (Pap) tests and screening for glandular neoplasia remain challenging. METHODS: Pap tests with an AGC interpretation from January 2008 to December 2013 were retrieved from a pathology database, and cases with histologic follow-up within 1 year were included in the study. RESULTS: There were 589,830 Pap tests during the study period, and 3709 cases (0.6%) were reported as AGC, which included the following: AGC, not otherwise specified (52.0%); atypical endocervical cells (28.0%); and other categories. There were 3007 cases (81.1%) with histologic follow-up results within 1 year. Cervical intraepithelial neoplasia 2/3 (CIN2/3), cervical adenocarcinoma in situ (AIS)/adenocarcinoma, and endometrial carcinoma were identified in 5.6%, 1.9%, and 5.5% of cases, respectively. Glandular neoplasia was more likely to be identified in cases with pure AGC subcategories than cases with AGC and squamous abnormalities. Endometrial neoplasia was more likely to be identified in cases with atypical endometrial cells than other categories. Overall, the most common severe abnormality on histologic follow-up was CIN2/3. Although CIN2/3 was the most common severe lesion in patients younger than 30 years (10.0%) and in patients aged 30 to 49 years (6.4%), endometrial carcinoma was the most common lesion in women who were 50 years old or older (13.7%). Endocervical glandular lesions (AIS and adenocarcinoma) occurred in only 1.9% of women. CONCLUSIONS: AGC subtypes and ages significantly affect histological follow-up results; 90.5% of cases with carcinoma on histologic follow-up were either endometrial or metastatic carcinoma. This study supports the recommendation that women with AGC Pap test results should be followed up with both endocervical and endometrial sampling. Cancer Cytopathol 2016;124:589-95. © 2016 American Cancer Society.

Clinical performance of the Food and Drug Administration-Approved high-risk HPV test for the detection of high-grade cervicovaginal lesions.

BACKGROUND: In recent years, high-risk human papillomavirus (hrHPV) testing for triaging atypical squamous cells of undetermined significance and cotesting with cytology have been implemented in clinical practice. However, clinical data for primary screening with human papillomavirus (HPV) testing alone are currently lacking. METHODS: This study retrospectively reviewed the correlation of cytology, histology, and hrHPV testing through the use of a cytology laboratory quality assurance database with 130,648 Papanicolaou (Pap) tests interpreted at Houston BioReference Laboratories and Houston Methodist Hospital between March 1, 2013 and June 30, 2014. Among the 47,499 patients who had undergone cytology-HPV cotesting, 1654 underwent follow-up biopsies. RESULTS: The sensitivities of the hrHPV and Pap tests were 80.8% and 81.2%, respectively, for detecting any type of cervicovaginal dysplasia and 91.3% and 90.9%, respectively, for high-grade cervicovaginal lesions. For biopsy-confirmed high-grade cervicovaginal lesions (cervical intraepithelial neoplasia grade 2+, adenocarcinoma in situ, or carcinoma; n = 253), the false-negative rates for hrHPV and Pap tests were 8.7% and 9.1%, respectively. The false-negative rate for cytology-hrHPV cotesting was only 1.2%. CONCLUSIONS: In clinical practice, the hrHPV test alone is not significantly superior to the Pap test as a primary screening method for cervicovaginal lesions. The false-negative rate of the hrHPV test in detecting biopsy-confirmed high-grade cervicovaginal lesions is comparable to the rate of the Pap test. Women with cytology and hrHPV cotesting, however, have a significantly lower false-negative rate than those undergoing either test alone. Currently, cytology-HPV cotesting remains the best strategy for detecting high-grade cervicovaginal lesions. Cancer Cytopathol 2016;124:317-23. © 2016 American Cancer Society.

Prior high-risk HPV testing and Pap test results for 427 invasive cervical cancers in China's largest CAP-certified laboratory.

BACKGROUND: Cervical cancer and its precursor lesions are caused by a persistent high-risk human papillomavirus (hrHPV) infection. hrHPV testing has been reported to have higher sensitivity than Papanicolaou (Pap) testing for the detection of cervical precursor lesions. However, limited data are available for prior human papillomavirus (HPV) testing results for patients later diagnosed with invasive cervical cancer, especially in countries lacking a national cervical cancer screening program such as China. This study investigated prior hrHPV testing results for patients with invasive cervical cancer in China. METHODS: Cases with a histologic diagnosis of invasive cervical carcinoma were retrieved from Guangzhou KingMed Diagnostics (the largest independent pathology laboratory in China); prior hrHPV and Pap test results obtained within the year before the cancer diagnosis were recorded. RESULTS: HPV testing was negative in 7.5% of 427 cases of invasive cervical carcinoma, including squamous cell carcinoma (5%) and adenocarcinoma (25%). In 155 cervical cancer cases with prior hrHPV and Pap testing, the negative rate for Pap testing was 1.9%, and the negative rate for HPV was 9.7%. Furthermore, when only cases of adenocarcinoma (n = 18) were examined, both the hrHPV-negative rate and the Pap-negative rate were higher at 33% and 5.6%, respectively. CONCLUSIONS: These data demonstrate a considerable prior hrHPV-negative rate and a lower prior Pap-negative rate in patients with invasive cervical carcinoma (especially adenocarcinoma) from a population of women without access to an established screening program.