BACKGROUND:We demonstrated that cervical cancer risk following any screening result is lower if there is a known prior negative screening history vs an unknown screening history. We extended these findings to look at how screening performs following repeatedly negative screening results. METHODS:Approximately 1.7 million women aged 30-64 years underwent triennial human papillomavirus (HPV) and cytology co-testing from 2003 to 2021. We modeled 5-year risks of cervical intraepithelial neoplasia grade 3 or more severe diagnoses (CIN3+) and invasive cervical cancer for the initial co-test, and then successive rounds following negative co-testing. A logistic-Weibull prevalence-incidence model was used to model risks. RESULTS:HPV test positivity was greater than cytology positivity for only the first co-test, and both positivity rates decreased with each screening round. Diagnostic yields of CIN3+ and cancer declined with each round of screening so the first screen yielded 8-fold more CIN3+ and invasive cancer than the fifth screen following 4 consecutive negative co-tests. Five-year risks of CIN3+ for positive and negative HPV and cytology results, individually or combined, decreased considerably after the first screen, with smaller decreases in each subsequent round. For cancer, we noticed a considerable decrease with the first screen only. Five-year CIN3+ risks were greater for positive HPV or cytology results, with a longer antecedent screening interval and younger age at screening (Ptrend < .001). CONCLUSIONS:Triennial screening that includes HPV testing becomes inefficient after a single and more so after multiple negative screens. These data support the use of longer screening intervals, especially following negative screen(s).

Human papillomavirus type 16 (HPV16) causes more cancer than any other virus. However, most HPV16 infections are controlled by the host's immune system and it remains unclear how viral and host genetic variation contribute to infection outcomes. Here, we analyze 4704 HPV16 whole genomes to identify 56 viral codons putatively under positive natural selection to change their amino acids, with evidence including dN/dS > 1, evolutionary convergence, and structural importance in the protein. We find that codons under positive selection disproportionately overlap known HPV16 immune epitopes recognized by cytotoxic T lymphocytes, particularly those restricted by the previously reported risk allele HLA-B*07:02 (odds ratio [OR] = 4.9; 95%CI = 2.1-10.3; PFisher = 0.00015), exemplified by position 10 of the E6 oncoprotein. Positively selected codons also disproportionately overlap 158 nucleotide sites at which the evolutionary sub/lineages of HPV16 have diverged (OR = 19.1; 95%CI = 10.5-34.7; PFisher < 2.2×10-16), and show more rare variation in cervical precancers/cancers than controls (benign or cleared HPV16 infections) in the E1 protein (OR = 9.34, 95%CI = 1.4-402.5; PFisher = 0.0084). Our results suggest that a small subset of HPV16 variants can improve viral persistence through escape of HLA-related immune recognition. The interaction of HPV16 and HLA variation may help to explain how similar or identical viral isolates can have such disparate infection outcomes.

Purpose Primary human papillomavirus (HPV) testing has the best tradeoff of benefits and harms for cervical screening but requires triage to determine management among HPV positives. We conducted a prospective observational study to evaluate triage of women who are HPV-positive using dual stain (DS) and HPV genotyping. Materials and Methods We included 9,645 consecutive women who are HPV-positive undergoing cervical screening in two periods between 2015 and 2017 in the organized cervical screening program at Kaiser Permanente Northern California. Absolute risk and clinical performance of DS and cytology for detection of cervical intraepithelial neoplasia grade 3 and greater (CIN3+) were estimated overall and by HPV genotype and by age. Cumulative absolute risk of CIN3+ was modeled over 5 years using a prevalence-incidence mixture model, which allows estimating risk accounting for differences in disease ascertainment, surveillance intervals, and compliance. Results The baseline risk of CIN3+ was 9.4% and 0.8% for women testing positive and negative for DS, respectively, and 6.9% and 2.0% for women testing positive and negative for cytology, respectively. Sensitivity, specificity, and predictive values for CIN3+ detection were better for DS compared with cytology over 5 years (P < .001 for all comparisons). Risk in women with HPV16-positive/negative for intraepithelial lesion or malignancy was substantially higher than the risk in women with HPV16-positive/DS-negative (7.5% v 2.9%, P < .001). DS had better triage performance compared with cytology in all age groups and in women positive for HPV types other than HPV16 or HPV18. Conclusion Long-term reassurance of low risk among DS negatives suggests that DS detects molecular changes earlier in the carcinogenic pathway than cytology. DS has better risk stratification than cytology overall, within HPV risk strata, and across all screening age groups and is a better option for triage of vaccinated populations.

Screening tests are crucial for detecting diseases at preclinical stages when timely intervention can prevent progression to more severe conditions. Advances in technology have facilitated developing screening tests based on novel markers, but evaluating their performance using biospecimens from large cohorts remains logistically complex and financially demanding. Two-phase designs offer a cost-effective solution by allowing inference when expensive marker measurements are collected on only a carefully selected subsample. While traditional two-phase designs have primarily targeted estimation of marker-outcome associations, they can effectively be extended to evaluate the clinical performance of a test, including estimation of positive predictive value (the risk in test positives) and complementary negative predictive value (the risk in test negatives). We propose a novel two-phase design for efficiently evaluating the risk-stratification utility of screening tests in distinguishing between high- and low-risk individuals for both current and future disease. Designed for use with biospecimens collected from screening studies, our methodology accommodates cohorts that include both pre-existing cases at an initial screening visit and new cases identified during follow-up. We demonstrate the efficiency gains of our proposed design compared to other subsampling schemes through simulation and illustrate its application in a motivating study evaluating the p16/ki-67 dual-stain test for managing human papillomavirus-positive women in cervical cancer screening. Data and stored biospecimen samples from Kaiser Permanente Northern California are used in this analysis.

Objective The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of extended genotyping results in cervical cancer prevention programs. Methods Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated using data obtained with the Onclarity HPV Assay from large cohorts. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Risk estimates were reviewed in relation to clinical action thresholds 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 Colposcopy is recommended after positive tests for human papillomavirus (HPV) types 16 and 18. For those positive for HPV 45, 33/58, 31, 52, 35/39/68, or 51 but negative for 16 or 18, triage with cytology or dual stain testing is recommended. When screening with primary HPV testing, for patients who test positive for HPV types 56/59/66 and no other carcinogenic types, repeat HPV testing in 1 year is recommended. When screening with cotesting, for those who test positive for HPV types 56/59/66 and no other carcinogenic types, 1-year return is recommended for negative for intraepithelial lesion or malignancy, atypical squamous cells of undetermined significance, and low-grade squamous intraepithelial lesion, and colposcopy is recommended for atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), atypical glandular cells, high-grade squamous intraepithelial lesion, or carcinoma. When patients without prior high-grade cytology (atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, atypical glandular cells, high-grade squamous intraepithelial lesion, or carcinoma) or histology (cervical intraepithelial neoplasia [CIN]2, CIN3, or adenocarcinoma in situ) are being followed, use of extended genotyping results is acceptable. When high-grade cytology or histology results are present, or when patients are being followed after treatment of CIN2+, management using the 2019 guidelines is recommended. Conclusions Human papillomavirus extended genotyping can guide clinical management in the setting of a positive HPV test result.

Human papillomavirus type 45 (HPV45) causes ~6% of all cervical cancers and an even greater proportion of adenocarcinomas, the latter of which are challenging to detect using current cervical cancer screening. Little is known about how HPV45 genetic variation is related to the risk of cervical precancer/cancer. To investigate this, we whole-genome sequenced a total of 1,083 HPV45-positive samples from two large studies. We evaluated associations of HPV45 genetic variation (sublineages, subclades, and SNPs) with histology-specific precancer/cancer risk using logistic regression and evaluated risk modification by self-reported race/ethnicity. Compared to the common A1 sublineage, A2 and B1 were associated with increased precancer/cancer (A2, OR = 3.9, 95% CI = 1.9-8.5; B1, OR = 2.7, 95% CI = 1.3-5.8; B2, OR = 3.3, 95% CI = 1.6-7.3), and most strongly with the glandular precancers/cancers (AIS/ADC; A2, OR = 6.9, 95% CI = 1.0-184; B1, OR = 6.2, 95% CI = 1.1-159). The A2 sublineage was most prevalent in women in East Asia and women who self-reported as Asian/Pacific Islander (PI) in the U.S.; East Asian and Asian/PI women had the greatest precancer/cancer risk associated with A2 infections (OR = 5.8, 95% CI = 1.3-37.4) compared to all other sublineages among these women. We further evaluated precancer/cancer risk associations for 262 individual HPV45 SNPs and identified four SNPs significantly associated with only glandular precancers/cancers after correction for multiple tests (ORs ranged 7.8-20.7). One of these SNPs was a nonsynonymous variant in both overlapping viral E2/E4 ORFs. In summary, we show that HPV45 genetic variation influences the risk of precancer/cancer, specifically glandular precancer/cancer. Further studies of these genetic variants may improve our understanding of glandular lesions.

Dual-stain cytology, using p16 and Ki67, is superior to conventional PAP cytology for triage of HPV-positive test results in cervical cancer screening. Its AI-based evaluation can remove subjectivity, improve performance and facilitate implementation. Using 5,722 dual-stain slides from population-based screening cohorts, we developed and validated Cytoreader-V2. In the SurePath Kaiser Implementation Study, Cytoreader-V2 achieved 87.2%/57.8% (sensitivity/specificity) compared to 89.9/52.6 (manual DS) and 85.8/41.9 (Pap cytology). In the Thin-Prep Biopsy Study, it reached 95.7/44.4 versus 89.4/35.0 (manual DS), and in anal DS cytology slides, 87.0/41.3 compared to 87.0/27.7 (manual). Robustness testing demonstrated significant stability across image transformations. Cytoreader-V2 improves specificity and reproducibility compared to manual dual-stain reading while maintaining high sensitivity. Its adaptability across populations with consistent performance makes it scalable for diverse clinical settings. Cytoreader-V2 can be a transformative tool in global cervical cancer screening as a critical AI applications in digital pathology.

Because of many factors, the landscape of cervical cancer prevention is again at a pivot point within the United States. Primary human papillomavirus (HPV) screening has been recommended as the preferred testing method by the American Cancer Society since 2020. Although primary HPV testing provides high negative predictive value in screening, women who screen positive for HPV need triage using methods that have an optimal balance between sensitivity for precancer and the number of colposcopies required for detection. The triage test ideally should maximize specificity while also reassuring patients who test negative, although it should be acknowledged that no screening or triage test can entirely exclude disease in a screen-positive patient. While cervical cytology (the Papanicolaou test) triage of primary HPV screen-positive patients is currently recommended by most screening strategies, additional triage tests, specifically extended HPV genotyping and combined p16/Ki-67 dual-stain immunocytochemistry, are now approved by the US Food and Drug Administration and incorporated into cervical cancer screening and management guidelines. Incorporating these triage methods into practice should be achieved by using appropriate validation/verification and implementation steps and, in the case of dual-stain immunocytochemistry, appropriate cytologist/cytopathologist training. The US Food and Drug Administration approval of vaginal self-collection in May 2024 is another significant advance for increasing access to screening. These samples can only be tested using primary HPV screening platforms, and guidance for management has been endorsed by the ASCCP's enduring guidelines process. This review discusses issues that warrant consideration before implementation and provides practical guidance for the incorporation of self-collected specimens and extended genotyping/dual-stain tests into the workflow of the cytopathology laboratory.

Abstract Introduction: Persistent infection with a high-risk HPV (HR-HPV) type causes cervical cancer and many other cancers in both men and women. Our published data have shown that the distribution of specific HPV16/35 sublineages and genetic variants differ around the world and confer greater risk of cervical precancer/cancer in the populations where the virus is thought to have originated and coevolved. More studies are needed to evaluate the relationship between race/ethnicity, HR-HPV genetic variation, and precancer/cancer risk. Objective: To evaluate HPV45 and HPV52 genetic variation, and how it relates to a woman’s race/ethnicity and cervical precancer/cancer risk, using HPV whole-genome sequencing of 774 HPV45+ and 719 HPV52+ women in the NCI-Kaiser Permanente Northern California (KPNC) HPV Persistence and Progression cohort; and compared to HPV16/35. Methods: We viral genome sequenced 557 HPV45+ and 345 HPV52+ controls (women with benign infections [≤CIN1]), and 94 HPV45+ and 227 HPV52+ precancer/cancer cases (CIN3+). We evaluated HPV45 and HPV52 prevalence for each type by a woman’s self-reported race/ethnicity, and compared them to HPV16 and HPV35 using existing comparable NCI-KPNC data. To assess associations between HPV45 and HPV52 genetic variation (viral sublineages and SNPs) and infection outcome, we used Fisher’s Exact Tests and logistic regression to estimate the OR and 95% CI. Results: For HPV45, we determined that sublineages have varying histology-specific precancer/cancer risk (ORs ranged from 2-14), and that the sublineage distribution significantly varied by race/ethnicity (p < 0.001). By race, the HPV45 A2 sublineage was most prevalent in Asian/PI women and was associated with the highest risk of CIN3+ in these women compared to other races/ethnicities (OR=5.7, 95% CI=1.5-29.4), while the B2 sublineage was associated with increased risk of CIN3+ in Black women only (OR=6.1, 95% CI=1.2-33.6). The prevalence of each HR-HPV type (HPV16/35/45/52) significantly varied by race/ethnicity (p < 0.001). For each type, White was the most reported race/ethnicity; however, Black women were a greater proportion of the HPV35+ cases compared to other types (15% vs 8-10%), and Asian/PIs were a greater proportion of HPV52+ cases (26% vs 10-13%). HPV52 genome analyses are still underway; we will present the complete study results (i.e., sublineage risk by race) at AACR. Conclusions: We conducted the largest studies of HPV45 and HPV52 genome variation to date. We demonstrate that specific HPV45 sublineages vary by race and are associated with an increased risk of precancer/cancer for specific races/ethnicities, and that HPV52 infection has a greater prevalence in Asian/PI women compared to other racial groups. Our data suggest that certain HR-HPV types and specific sublineages of these types are more common in specific racial/ethnic groups and potentially linked to differing risks by race. Citation Format: Aimee J. Koestler, Chase W. Nelson, Meredith Yeager, Zigui Chen, Laurie Burdett, Sambit K. Mishra, Michael Dean, Elizabeth Suh-Burgmann, Thomas Lorey, Phillip E. Castle, Mark Schiffman, Lisa Mirabello. HPV45 and HPV52 prevalence, within-type variants, and precancer/cancer risks differ by race/ethnicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3948.

Implementation of primary human papillomavirus (HPV) testing has been slow in the United States perhaps because of concerns of decreased sensitivity compared with concurrent HPV and cytology testing ("cotesting"). We used the National Breast and Cervical Cancer Early Detection Program and the Kaiser Permanente of Northern California cohort to quantify potential trade-offs with primary HPV compared with cotesting in 4 US populations with differing precancer or cancer prevalence. In all settings, cotesting required more lab tests and more colposcopies compared with primary HPV testing. Additional cervical intraepithelial neoplasia grade 3 or cancer immediately detected from cotesting vs primary HPV decreased with decreasing population-average cervical intraepithelial neoplasia grade 3 or cancer prevalence from 71 per 100 000 screened among never or rarely screened individuals in the National Breast and Cervical Cancer Early Detection Program (prevalence = 1212 per 100 000) to 4 per 100 000 screened among individuals with prior HPV-negative results in Kaiser Permanente of Northern California (prevalence = 86 per 100 000). These data suggest that cotesting confer an unfavorable benefit-to-harm ratio over primary HPV testing.

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 de fi ning 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 insigni fi cant variability between swabs self-collected by the same individual ( n = 15 participants collecting 5 swabs per participant), measured by ampli fi cation of HPV and human 13-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 amplifi cation 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 ampli fi cation for 13-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 in fl uence HPV detection. Furthermore, lack of 13-globin ampli fi cation in HPV-negative samples accurately identi fi ed participants who required recollection.

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.

Journal Article Commentary on You Will Not Believe What We Found in the Urine Sediment Get access Thomas S Lorey Thomas S Lorey The Permanente Medical Group, Kaiser Permanente Northern California, Berkeley, CA, United States Address correspondence to this author at: Kaiser Permanente Regional Laboratory, 1725 Eastshore Hwy, Berkeley, CA 94710, United States. E-mail thomas.lorey@kp.org. https://orcid.org/0000-0002-9075-1515 Search for other works by this author on: Oxford Academic Google Scholar The Journal of Applied Laboratory Medicine, Volume 9, Issue 3, May 2024, Pages 639–640, https://doi.org/10.1093/jalm/jfae004 Published: 05 March 2024 Article history Received: 05 December 2023 Accepted: 11 December 2023 Published: 05 March 2024

Journal Article Commentary on Discrepant Potassium Levels in a Young Female: A Case Report Get access Thomas S Lorey Thomas S Lorey Regional Laboratory, Kaiser Permanente Northern California, Berkeley, CA, United States Address correspondence to this author at: Kaiser Permanente Regional Laboratory, 1725 Eastshore Hwy, Berkeley, CA 94710, United States. E-mail thomas.lorey@kp.org. https://orcid.org/0000-0002-9075-1515 Search for other works by this author on: Oxford Academic Google Scholar The Journal of Applied Laboratory Medicine, jfae078, https://doi.org/10.1093/jalm/jfae078 Published: 30 July 2024 Article history Received: 24 June 2024 Accepted: 26 June 2024 Published: 30 July 2024

Invasive cervical cancers (ICC), caused by HPV infections, have a heterogeneous molecular landscape. We investigate the detection, timing, and HPV type specificity of somatic mutations in 3929 HPV-positive exfoliated cervical cell samples from individuals undergoing cervical screening in the U.S. using deep targeted sequencing in ICC cases, precancers, and HPV-positive controls. We discover a subset of hotspot mutations rare in controls (2.6%) but significantly more prevalent in precancers, particularly glandular precancer lesions (10.2%), and cancers (25.7%), supporting their involvement in ICC carcinogenesis. Hotspot mutations differ by HPV type, and HPV18/45-positive ICC are more likely to have multiple hotspot mutations compared to HPV16-positive ICC. The proportion of cells containing hotspot mutations is higher (i.e., higher variant allele fraction) in ICC and mutations are detectable up to 6 years prior to cancer diagnosis. Our findings demonstrate the feasibility of using exfoliated cervical cells for detection of somatic mutations as potential diagnostic biomarkers. Invasive cervical cancer is caused by HPV infection, but the disease itself is highly variable. Here, the authors use deep targeted sequencing to identify hotspot mutations in routine screening samples prior to diagnosis, which differed depending on HPV type.

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.

BACKGROUND:Individuals with obesity have an increased risk of cervical cancer, in part related to challenges associated with cervical sampling and visualization that result in missed detection of cervical precancers. The influence of obesity on the effectiveness of excisional treatment of detected cervical precancers and posttreatment disease risk is unknown. OBJECTIVE:The aim of this study was to evaluate posttreatment risks of cervical precancer and cancer by body mass index (BMI). STUDY DESIGN:This retrospective cohort study included individuals aged 25 years and older undergoing excisional treatment for cervical precancer, either cervical intraepithelial neoplasia (CIN) grade 2 or 3 or adenocarcinoma in situ as of January 2017 with follow-up through February 2023. Patients were excluded if they were missing BMI, had cancer upon excision or had hysterectomy in lieu of excision, or were missing a valid referral screening visit. We categorized BMI as follows: underweight/normal (<25 kg/m2), overweight (25 to <30 kg/m2), and obesity (≥30kg/m2), as well as by class (I-III) of obesity. We calculated 2-year risks of CIN3 and cancer (combined as CIN3+) using Kaplan Meier methods and evaluated multivariable adjusted associations of BMI with CIN3+ using Cox Proportional Hazards regression analyses, accounting for age at treatment, race and ethnicity, and treatment type. RESULTS:Among 10,614 patients, a total of 680 (6.4%) developed post-treatment CIN3+; most (91%) within 2 years of treatment. Two-year CIN3+ and cancer risks were highest in those with obesity (8.65%, 95% CI, 7.6%-9.9% and 0.79%, 95% CI, 0.5%-1.2%, respectively) and lowest in those with normal weight (5.57%, 95% CI, 4.9%-6.3% and 0.29%, 95% CI, 0.2%-0.5%, respectively). Hazard ratios measuring associations of BMI with risk of posttreatment CIN3+ ranged from 1.19 (95% CI, 1.0-1.4) among those with overweight to 1.89 (95% CI, 1.4-2.6) among those with class III obesity (P-trend<.0001). A similar trend was observed for cancer, from 1.62 (95% CI, 0.8-3.3) for overweight and 3.50 (95% CI, 1.3-9.3) for class III obesity (P-trend=.016). CONCLUSION:Patients with obesity undergoing excisional treatment for cervical precancer have a higher risk of residual or recurrent disease, likely due to incomplete excision.

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.

Table S1 shows type-specific associations of methylation with CIN3/AIS. Table S2 shows the correlation of methylation across CpG sites, by HPV type