Primary human papillomavirus testing versus CO-testing: clinical outcomes in populations with different disease prevalence.

Implementation of primary human papillomavirus (HPV) testing has been slow in the US perhaps due to concerns of decreased sensitivity compared with concurrent HPV and cytology testing (cotesting). We used the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) and the Kaiser Permanente of Northern California (KPNC) cohort to quantify potential trade-offs with primary HPV compared with cotesting in four US populations with differing precancer/cancer prevalence. In all settings, cotesting required more lab tests and more colposcopies compared to primary HPV testing. Additional cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) immediately detected from cotesting vs primary HPV decreased with decreasing population-average CIN3+ prevalence, from 71 per 100,000 screened among never/rarely screened individuals in the NBCCEDP (prevalence = 1,212 per 100,000) to 4 per 100,000 screened among individuals with prior HPV-negative results in KPNC (prevalence = 86 per 100,000). These data suggest that cotesting confer an unfavorable benefit-to-harm ratio over primary HPV testing.

Evaluation of Pre-Analytical Variables for Human Papillomavirus Primary Screening from Self-Collected Vaginal Swabs.

Human papillomavirus (HPV) primary screening is an effective approach to assessing cervical cancer risk. Self-collected vaginal swabs can expand testing access, but the data defining analytical performance criteria necessary for adoption of self-collected specimens are limited, especially for those occurring outside the clinic, where the swab remains dry during transport. Here, we evaluated the performance of self-collected vaginal swabs for HPV detection using the Cobas 6800. There was insignificant variability between swabs self-collected by the same individual (n = 15 participants collecting 5 swabs per participant), measured by amplification of HPV and human ß-globin control DNA. Comparison of self-collected vaginal swab and provider-collected cervical samples (n = 144 pairs) proved highly concordant for HPV detection (total agreement = 90.3%; positive percentage agreement = 84.2%). There was no relationship between the number of dry storage days and amplification of HPV (n = 68; range, 4 to 41 days). Exposure of self-collected dry swabs to extreme summer and winter temperatures did not affect testing outcomes. A second internal control (RNase P) demonstrated that lack of amplification for ß-globin from self-collected specimens was consistent with poor, but not absent, cellularity. These data suggest that self-collected vaginal samples enable accurate clinical HPV testing, and that extended ambient dry storage or exposure to extreme temperatures does not influence HPV detection. Furthermore, lack of ß-globin amplification in HPV-negative samples accurately identified participants who required recollection.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. RESULTS: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. CONCLUSIONS: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

Calendar-period trends in cervical precancer and cancer diagnoses since the introduction of human papillomavirus and cytology co-testing into routine cervical cancer screening at Kaiser Permanente Northern California.

OBJECTIVES: The longer-term impact of introducing human papillomavirus (HPV) testing into routine cervical cancer screening on precancer and cancer rates by histologic type has not been well described. Calendar trends in diagnoses were examined using data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in 2003 for women aged ≥30 years. METHODS: We examined trends in cervical precancer (cervical intraepithelial neoplasia grade 3 [CIN3] and adenocarcinoma in situ [AIS]) and cancer (squamous cell carcinoma [SCC] and adenocarcinoma [ADC]) diagnoses per 1000 screened during 2003-2018. We examined ratios of squamous vs. glandular diagnoses (SCC:ADC and CIN3:AIS). RESULTS: CIN3 and AIS diagnoses increased approximately 2% and 3% annually, respectively (ptrend < 0.001 for both). While SCC diagnoses decreased by 5% per annually (ptrend < 0.001), ADC diagnoses did not change. These patterns were generally observed within each age group (30-39, 40-49, and 50-64 years). ADC diagnoses per 1000 screened did not change even among those who underwent co-testing starting in 2003-2006. SCC:ADC decreased from approximately 2.5:1 in 2003-2006 to 1.3:1 in 2015-2018 while the CIN3:AIS remained relatively constant, ∼10:1. CONCLUSIONS: Since its introduction at KPNC, co-testing increased the detection of CIN3 over time, which likely caused a subsequent reduction of SCC. However, there has been no observed decrease in ADC. One possible explanation for lack of effectiveness against ADC is the underdiagnosis of AIS. Novel strategies to identify and treat women at high risk of ADC need to be developed and clinically validated.

AACC/NKF Guidance Document on Improving Equity in Chronic Kidney Disease Care.

BACKGROUND: Kidney disease (KD) is an important health equity issue with Black, Hispanic, and socioeconomically disadvantaged individuals experiencing a disproportionate disease burden. Prior to 2021, the commonly used estimated glomerular filtration rate (eGFR) equations incorporated coefficients for Black race that conferred higher GFR estimates for Black individuals compared to non-Black individuals of the same sex, age, and blood creatinine concentration. With a recognition that race does not delineate distinct biological categories, a joint task force of the National Kidney Foundation and the American Society of Nephrology recommended the adoption of the CKD-EPI 2021 race-agnostic equations. CONTENT: This document provides guidance on implementation of the CKD-EPI 2021 equations. It describes recommendations for KD biomarker testing, and opportunities for collaboration between clinical laboratories and providers to improve KD detection in high-risk populations. Further, the document provides guidance on the use of cystatin C, and eGFR reporting and interpretation in gender-diverse populations. SUMMARY: Implementation of the CKD-EPI 2021 eGFR equations represents progress toward health equity in the management of KD. Ongoing efforts by multidisciplinary teams, including clinical laboratorians, should focus on improved disease detection in clinically and socially high-risk populations. Routine use of cystatin C is recommended to improve the accuracy of eGFR, particularly in patients whose blood creatinine concentrations are confounded by processes other than glomerular filtration. When managing gender-diverse individuals, eGFR should be calculated and reported with both male and female coefficients. Gender-diverse individuals can benefit from a more holistic management approach, particularly at important clinical decision points.

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.

BACKGROUND: Cervical 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. METHODS: Kaiser 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. RESULTS: Among 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. CONCLUSION: Detection of HPV 16/18/45 positivity elevates risk of adenocarcinoma, particularly if AGC cytology is also found.

Effective Access to Laboratory Test Results: A Health Equity Issue that Enhances Diagnostic Excellence.

Access to laboratory test results through patient portals is a health equity issue for patients with limited English proficiency (LEP), particularly for Spanish-speaking patients, the largest minority group in the USA. Gaps ranging from linguistic, cultural, and socioeconomic disparities to lack of systematic approaches (e.g., implementation of specific support protocols, policies) are among the identified factors that limit LEP patients' access to patient portals. This paper summarizes initiatives healthcare providers, laboratory professionals, and portal developers can use to address disparities that affect >26 million LEPs while improving their health equity.

Using Natural Language Processing to Improve Discrete Data Capture From Interpretive Cervical Biopsy Diagnoses at a Large Health Care Organization.

CONTEXT.­: The terminology used by pathologists to describe and grade dysplasia and premalignant changes of the cervical epithelium has evolved over time. Unfortunately, coexistence of different classification systems combined with nonstandardized interpretive text has created multiple layers of interpretive ambiguity. OBJECTIVE.­: To use natural language processing (NLP) to automate and expedite translation of interpretive text to a single most severe, and thus actionable, cervical intraepithelial neoplasia (CIN) diagnosis. DESIGN.­: We developed and applied NLP algorithms to 35 847 unstructured cervical pathology reports and assessed NLP performance in identifying the most severe diagnosis, compared to expert manual review. NLP performance was determined by calculating precision, recall, and F score. RESULTS.­: The NLP algorithms yielded a precision of 0.957, a recall of 0.925, and an F score of 0.94. Additionally, we estimated that the time to evaluate each monthly biopsy file was significantly reduced, from 30 hours to 0.5 hours. CONCLUSIONS.­: A set of validated NLP algorithms applied to pathology reports can rapidly and efficiently assign a discrete, actionable diagnosis using CIN classification to assist with clinical management of cervical pathology and disease. Moreover, discrete diagnostic data encoded as CIN terminology can enhance the efficiency of clinical research.

Distribution of High-Sensitivity Cardiac Troponin and N-Terminal Pro-Brain Natriuretic Peptide in Healthy Transgender People.

Importance: Sex-specific differences in the commonly used cardiac biomarkers high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are apparent. There is an absence of medical literature delineating the concentration differences for these biomarkers in transgender individuals without cardiac disease. Objective: To determine the distribution of hs-cTn and NT-proBNP in healthy transgender people. Design, Setting, and Participants: In this cross-sectional prospective study, healthy transgender individuals prescribed testosterone or estradiol for 12 months or more were recruited from internal medicine and primary care clinics that specialize in transgender medical care between November 1, 2017, and July 1, 2018. Exposures: Testosterone or estradiol for 12 months. Main Outcomes and Measures: Concentrations for hs-cTnI (troponin I), hs-cTnT (troponin T), and NT-proBNP were measured. Results: Transgender people prescribed testosterone (n = 79; mean [SD] age, 28.8 [7.8] years) or estrogen (n = 93; mean [SD] age, 35.1 [11.7] years) were recruited. The concentration of hs-cTn was significantly higher in transgender men relative to transgender women. For Abbott hs-cTnI levels, the median (IQR) concentration observed in transgender men and women was 0.9 (0.6-1.7) ng/L and 0.6 (0.3-1.0) ng/L, respectively. Results were similar across 2 additional hs-cTn assays. In contrast, NT-proBNP level was higher in transgender women. The median (IQR) NT-proBNP concentration was significantly higher in transgender women ( 49 [32-86] ng/L) than in transgender men (17 [13-27] ng/L). Conclusions and Relevance: Findings of this cross-sectional study suggest that the differences in concentration for hs-cTn and NT-proBNP between transgender men and women were similar to what is observed between cisgender men and women. Sex hormones, rather than sex assigned at birth, may be a stronger driver of the observed concentration differences between healthy men and women for biomarkers of cardiac disease.

A comparison of high-grade cervical abnormality risks in women living with and without human immunodeficiency virus undergoing routine cervical-cancer screening.

As the US moves increasingly towards using human papillomavirus (HPV) testing with or without concurrent cytology for cervical cancer screening, it is unknown what the corresponding risks are following a screening result for women living with HIV (WLWH), which will dictate the optimal clinical follow-up. Therefore, using medical records data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in women aged 30-64 years in 2003, we compared risks of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe diagnoses (CIN2+) in women not known to have HIV (HIV[-] women) (n = 67,488) frequency matched 111:1 on age and year of the first co-test to the 608 WLWH (n = 608). WLWH were more likely to test HPV positive (20.2% vs. 6.5%, p < 0.001) and have non-normal cytology (14.1% vs. 4.1%, p < 0.001) than HIV[-] women. Five-year CIN2+ risks for all WLWH and HIV[-] women were 3.5% (95%CI = 2.0-5.0%) and 1.6% (95%CI = 1.5-1.8%) (p = 0.01), respectively. Five-year CIN2+ risks for WLWH with positive HPV and non-normal cytology, positive HPV and normal cytology, negative HPV and non-normal cytology, and negative HPV and normal cytology were 24.9% (95%CI = 13.4-36.4%), 3.0% (95%CI = 0.0-7.4%), 3.6 (95%CI = 0.0-9.8%) and 0.3% (95%CI = 0.0-0.8%), respectively. Corresponding 5-year CIN2+ risks for HIV[-] women were 26.6% (95%CI = 24.6-28.7%), 8.5% (95%CI = 7.2-9.9%), 1.9% (95%CI = 1.0-2.8%), and 0.5% (95%CI = 0.4-0.6%), respectively. Thus, in this healthcare setting, the main cause in overall CIN2+ risk differences between WLWH and HIV[-] women was the former was more likely to screen positive and once the screening result is known, it may be reasonable to manage both populations similarly.

Contribution of Etiologic Cofactors to CIN3+ Risk Among Women With Human Papillomavirus-Positive Screening Test Results.

OBJECTIVE: The US screening and management guidelines for cervical cancer are based on the absolute risk of precancer estimated from large clinical cohorts and trials. Given the widespread transition toward screening with human papillomavirus (HPV) testing, it is important to assess which additional factors to include in clinical risk assessment to optimize management of HPV-infected women. MATERIALS AND METHODS: We analyzed data from HPV-infected women, ages 30-65 years, in the National Cancer Institute-Kaiser Permanente Northern California Persistence and Progression study. We estimated the influence of HPV risk group, cytology result, and selected cofactors on immediate risk of cervical intraepithelial neoplasia grade 3 or higher (CIN 3+) among 16,094 HPV-positive women. Cofactors considered included, age, race/ethnicity, income, smoking, and hormonal contraceptive use. RESULTS: Human papillomavirus risk group and cytology test result were strongly correlated with CIN 3+ risk. After considering cytology and HPV risk group, other cofactors (age, race/ethnicity, income, smoking, and hormonal contraceptive use) had minimal impact on CIN 3+ risk and did not change recommended management based on accepted risk thresholds. We had insufficient data to assess the impact of long-duration heavy smoking, parity, history of sexually transmitted infection, or immunosuppression. CONCLUSIONS: In our study at the Kaiser Permanente Northern California, the risk of CIN 3+ was determined mainly by HPV risk group and cytology results, with other cofactors having limited impact in adjusted analyses. This supports the use of HPV and cytology results in risk-based management guidelines.

Automated Evaluation of p16/Ki-67 Dual-Stain Cytology as a Biomarker for Detection of Anal Precancer in Men Who Have Sex With Men and Are Living With Human Immunodeficiency Virus.

BACKGROUND: Human papillomavirus-related biomarkers such as p16/Ki-67 "dual-stain" (DS) cytology have shown promising clinical performance for anal cancer screening. Here, we assessed the performance of automated evaluation of DS cytology (automated DS) to detect anal precancer in men who have sex with men (MSM) and are living with human immunodeficiency virus (HIV). METHODS: We conducted a cross-sectional analysis of 320 MSM with HIV undergoing anal cancer screening and high-resolution anoscopy (HRA) in 2009-2010. We evaluated the performance of automated DS based on a deep-learning classifier compared to manual evaluation of DS cytology (manual DS) to detect anal intraepithelial neoplasia grade 2 or 3 (AIN2+) and grade 3 (AIN3). We evaluated different DS-positive cell thresholds quantified by the automated approach and modeled performance compared with other screening strategies in a hypothetical population of MSM with HIV. RESULTS: Compared with manual DS, automated DS had significantly higher specificity (50.9% vs 42.2%; P < .001) and similar sensitivity (93.2% vs 92.1%) for detection of AIN2+. Human papillomavirus testing with automated DS triage was significantly more specific than automated DS alone (56.5% vs 50.9%; P < .001), with the same sensitivity (93.2%). In a modeled analysis assuming a 20% AIN2+ prevalence, automated DS detected more precancers than manual DS and anal cytology (186, 184, and 162, respectively) and had the lowest HRA referral rate per AIN2+ case detected (3.1, 3.5, and 3.3, respectively). CONCLUSIONS: Compared with manual DS, automated DS detects the same number of precancers, with a lower HRA referral rate.

The Improving Risk Informed HPV Screening (IRIS) Study: Design and Baseline Characteristics.

BACKGROUND: Cervical cancer screening with high-risk human papillomavirus (HrHPV) testing is being introduced. Most HrHPV infections are transient, requiring triage tests to identify individuals at highest risk for progression to cervical cancer. Head-to-head comparisons of available strategies for screening and triage are needed. Endometrial and ovarian cancers could be amenable to similar testing. METHODS: Between 2016 and 2020, discarded cervical cancer screening specimens from women ages 25 to 65 undergoing screening at Kaiser Permanente Northern California were collected. Specimens were aliquoted, stabilized, and stored frozen. Human papillomavirus (HPV), cytology, and histopathology results as well as demographic and cofactor information were obtained from electronic medical records (EMR). Follow-up collection of specimens was conducted for 2 years, and EMR-based data collection was planned for 5 years. RESULTS: Collection of enrollment and follow-up specimens is complete, and EMR-based follow-up data collection is ongoing. At baseline, specimens were collected from 54,957 HPV-positive, 10,215 HPV-negative/Pap-positive, and 12,748 HPV-negative/Pap-negative women. Clinical history prior to baseline was available for 72.6% of individuals, of which 53.9% were undergoing routine screening, 8.6% recently had an abnormal screen, 30.3% had previous colposcopy, and 7.2% had previous treatment. As of February 2021, 55.7% had one or more colposcopies, yielding 5,563 cervical intraepithelial neoplasia grade 2 (CIN2), 2,756 cervical intraepithelial neoplasia grade 3 (CIN3), and 146 cancer histopathology diagnoses. CONCLUSIONS: This robust population-based cohort study represents all stages of cervical cancer screening, management, and posttreatment follow-up. IMPACT: The IRIS study is a unique and highly relevant resource allowing for natural history studies and rigorous evaluation of candidate HrHPV screening and triage markers, while permitting studies of biomarkers associated with other gynecologic cancers.

Development of a large biorepository of cervical specimens for the Improving Risk Informed HPV Screening study (IRIS).

INTRODUCTION: Biomarkers of Human Papillomavirus (HPV) cervical carcinogenesis are critical to address questions of how to triage and manage women who screen positive for high-risk HPV (HrHPV) and identify those at highest cancer risk. METHODS: We describe the development of a large biorepository of cervical specimens for the Improving Risk Informed HPV Screening Study (IRIS) using residual specimens collected in the regional laboratory from women aged 25 and older who had cervical cancer screening or follow-up testing with high-risk human papillomavirus (HrHPV) testing and liquid-based cytology (co-testing) at Kaiser Permanente Northern California (KPNC) from January 2016 to August 2018. Specimen selection, processing for long-term storage, follow-up tracking, consent and demographic and clinical characteristics of the women in the IRIS cohort are described. RESULTS: Selecting from 897,680 women who had at least one co-test during the study period, we collected 199,403 baseline and 216,390 follow-up HrHPV and cytology specimens from a stratified random sample of 81,348 women, of which 3,428 (4.2%) opted out of the study and were excluded. The majority (79.9%) of the baseline specimens were from HrHPV-positive women. The mean age was 36 years, and the cohort is racially/ethnically diverse with 56% of women being Hispanic or non-white. Over two-thirds of the cohort were members of KPNC for two or more years prior to inclusion. Of the 77,920 women included in the cohort, 57,414 (73.7%) had at least one follow-up co-test. CONCLUSION: Use of specimens from the biorepository will elucidate molecular mechanisms underlying HPV carcinogenesis and inform more effective screening and follow-up strategies.

Phylogenomic Analysis of Human Papillomavirus Type 31 and Cervical Carcinogenesis: A Study of 2093 Viral Genomes.

Human papillomavirus (HPV) type 31 (HPV31) is closely related to the most carcinogenic type, HPV16, but only accounts for 4% of cervical cancer cases worldwide. Viral genetic and epigenetic variations have been associated with carcinogenesis for other high-risk HPV types, but little is known about HPV31. We sequenced 2093 HPV31 viral whole genomes from two large studies, one from the U.S. and one international. In addition, we investigated CpG methylation in a subset of 175 samples. We evaluated the association of HPV31 lineages/sublineages, single nucleotide polymorphisms (SNPs) and viral methylation with cervical carcinogenesis. HPV31 A/B clade was >1.8-fold more associated with cervical intraepithelial neoplasia grade 3 and cancer (CIN3+) compared to the most common C lineage. Lineage/sublineage distribution varied by race/ethnicity and geographic region. A viral genome-wide association analysis identified SNPs within the A/B clade associated with CIN3+, including H23Y (C626T) (odds ratio = 1.60, confidence intervals = 1.17-2.19) located in the pRb CR2 binding-site within the E7 oncogene. Viral CpG methylation was higher in lineage B, compared to the other lineages, and was most elevated in CIN3+. In conclusion, these data support the increased oncogenicity of the A/B lineages and suggest variation of E7 as a contributing risk factor.

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

BACKGROUND: To investigate whether routine cervical screening using human papillomavirus (HPV) and cytology co-testing effectively identifies women with endometrial (EC) or ovarian (OvC) cancer. METHODS: In 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. RESULTS: Most 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%. CONCLUSIONS: Abnormal cervical screening tests, even AGC cytology, rarely precedes and poorly predict women with EC or OvC.