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.

Evaluation of Follow-up Colposcopy Procedures After Abnormal Cervical Screening Result Across a Statewide Study in Mississippi.

Purpose: Cervical screening is used to detect and treat precancers to prevent invasive cancers. However, successful prevention also requires adequate follow-up and treatment of individuals with abnormal screening results. The aim was to investigate demographics, clinical characteristics, and follow-up status for individuals needing colposcopy after an abnormal screening result. Methods: The STRIDES (Studying Risk to Improve DisparitiES) cohort comprises individuals undergoing cervical cancer screening and management at a Mississippi Health Department or University of Mississippi clinic. Follow-up status, demographics, and clinical data were assessed from electronic health records and, if necessary, patient navigation on individuals identified as needing a colposcopy after an abnormal screening. Results: Of the 1,458 individuals requiring colposcopy, 43.0% had the procedure within 4 months, 16.4% had a delayed procedure, and 39.5% had no documented follow-up, with significant predictors of follow-up identified as age and cytology diagnosis. Based on age, individuals 30 + were more likely to follow up with a colposcopy compared to individuals < 30 years (49% and 38.7%, respectively; p < .001). Individuals with cytology diagnoses of LSIL (52.9%), ASC-H (51.4%), and HSIL (62.3%) had higher percentages of adherence to follow-up colposcopy guidelines (p < .001). Conclusion: Despite high cervical cancer screening rates among Mississippians, a substantial portion did not have adequate next-step intervention. However, it is encouraging that highest risk individuals were more likely to have a colposcopy. Regardless, continuing to understand the underlying causes for incomplete follow-up is crucial for timely secondary targeted interventions to reduce cervical cancer burden, promote awareness, and improve health outcomes.

Trends in Sexual Risk Behavioral Responses among High School Students between Mississippi and the United States: 2001 to 2019 YRBSS.

BACKGROUND: Early sexual reproductive health (SRH) education is linked to a reduction in risky sexual behaviors. Sexually transmitted infections (STIs) are rising at alarming rates. Risky sexual behaviors, including initiation of sex before age 13, having more than four sexual partners, and lack of use of condoms, increase the chance of infection and cancer. Informing students about the link between risky behaviors and cancer is vital to reduce morbidity and mortality. METHODS: A trend analysis of the Youth Risk Behavior Surveillance System (YRBSS) data between 2001 and 2019 was conducted. Results from four survey responses related to sexual risk behaviors among 9th to 12th grade in Mississippi students are compared with their US peers. RESULTS: Between 2001 and 2019, favorable declines in 3 out of 4 sexual risk behaviors were observed. Declining prevalence was reported for "ever had sexual intercourse," "age of sexual initiation at age 13 or younger," and "having 4 or more sexual partners in their lifetime" are promising. However, fewer students report using condoms. The adjusted prevalence rates for Mississippi students in all 4 measures were higher than the national responses. CONCLUSIONS: Our analysis supports the need for early skill-based sex education to promote health. States with increased behavioral risk among students should consider trends in data to improve education and policy.

Post-kidney transplant cancers: Racial and ethnic differences in sun-exposed skin versus non-sun-exposed anogenital skin.

BACKGROUND: Transplant recipients have a 2- to 4-fold increased risk of developing malignancies over the general population. Cancer is the second most common cause of death for recipients. The magnitude of the risk depends on the cancer type and increases in viral-related malignancies. Skin cancer is the most common. However, data in most cancer registries is limited to cutaneous melanomas, thereby limiting the epidemiologic examination of cancer risk in non-melanoma skin cancer. Our goal was to evaluate post-kidney transplant cancer cases and sites in our population to guide screening recommendations. METHODS: Between 2009 and 2015, a retrospective study of adult kidney recipients transplanted at East Carolina University was conducted. The first cancer diagnosis after transplant through February 18, 2020, was captured and analyzed. Patient demographics, cancer sites, and histological diagnoses were analyzed and compared. p16 immunohistochemistry was used as a surrogate marker for high-risk human papillomavirus (HPV) infection. RESULTS: Retrospectively, kidney transplant recipients were analyzed (N = 439), the majority were non-Hispanic Black (NHB) individuals, 312 (71.1%), and 127 (28.9%) were non-Hispanic White (NHW) individuals. Of these, 59 (13.4%) developed a posttransplant malignancy, with the majority on sun-exposed skin found in NHW. NHB had all anogenital/mucosa skin cancers on non-sun-exposed skin. Of these detected in NHB, all were squamous cell carcinomas, with five out of six (83.3%) being positive for p16. CONCLUSIONS: Posttransplant malignancy differed significantly by race, site, and potential source of etiology. The majority of malignancies are likely explained by acceleration of precursor lesions from prior exposure to ultraviolet rays or HPV.

Age-specific prevalence of human papillomavirus and abnormal cytology at baseline in a diverse statewide prospective cohort of individuals undergoing cervical cancer screening in Mississippi.

BACKGROUND: Mississippi (MS) has among the highest rates of cervical cancer incidence and mortality in the United States, with disproportionately higher rates among Blacks compared to Whites. Here, we evaluate the prevalence of high-risk human papillomavirus (HPV) and abnormal cytology in a representative baseline sample from a diverse statewide cohort of individuals attending cervical screening in MS from the STRIDES Study (STudying Risk to Improve DisparitiES in cervical cancer). METHODS: We included individuals aged 21-65 years undergoing screening at the University of Mississippi Medical Center (UMMC) and the Mississippi State Department of Health (MSDH) from May to November 2018. We calculated age-specific HPV prevalence, overall and by partial HPV16/18 genotyping, and abnormal cytology by race. RESULTS: A total of 6871 individuals (mean age 35.7 years) were included. HPV prevalence was 25.6% and higher in Blacks (28.0%) compared to Whites (22.4%). HPV prevalence was significantly higher in Blacks aged 21-24 years (50.2%) and 30-34 years (30.2%) compared to Whites in the same age groups (32.1% and 20.7%; p < 0.0001, respectively). The prevalence of high-grade cytologic abnormalities, a cytologic sign of cervical precancer, peaked earlier in Blacks (ages 25-29) compared to Whites (35-39). For comparison, we also analyzed HPV prevalence data from the National Health and Nutrition Examination Survey (NHANES, 2013-2016) and observed similar racial differences in HPV prevalence among women aged 21-24 years. CONCLUSIONS: Our findings suggest that Blacks undergoing cervical cancer screening in MS have higher prevalence of other high-risk 12 HPV types at younger ages and experience an earlier peak of high-grade cytologic abnormalities compared to Whites.

STRIDES - STudying Risk to Improve DisparitiES in Cervical Cancer in Mississippi - Design and baseline results of a Statewide Cohort Study.

Cervical cancer rates in Mississippi are disproportionately high, particularly among Black individuals; yet, research in this population is lacking. We designed a statewide, racially diverse cohort of individuals undergoing cervical screening in Mississippi. Here, we report the baseline findings from this study. We included individuals aged 21 years and older undergoing cervical screening with cytology or cytology-human papillomavirus (HPV) co-testing at the Mississippi State Health Department (MSDH) and the University of Mississippi Medical Center (UMMC) (December 2017-May 2020). We collected discarded cytology specimens for future biomarker testing. Demographics and clinical results were abstracted from electronic medical records and evaluated using descriptive statistics and chi-square tests. A total of 24,796 individuals were included, with a median age of 34.8 years. The distribution of race in our cohort was 60.2% Black, 26.4% White, 7.5% other, and 5.9% missing. Approximately 15% had abnormal cytology and, among those who underwent co-testing at MSDH (n = 6,377), HPV positivity was 17.4% and did not vary significantly by race. Among HPV positives, Black individuals were significantly less likely to be HPV16/18 positive and more likely to be positive for other high-risk 12 HPV types compared to White individuals (20.5% vs. 27.9%, and 79.5% and 72.1%, respectively, p = 0.011). Our statewide cohort represents one of the largest racially diverse studies of cervical screening in the U.S. We show a high burden of abnormal cytology and HPV positivity, with significant racial differences in HPV genotype prevalence. Future studies will evaluate cervical precancer risk, HPV genotyping, and novel biomarkers in this population.

Racial differences in HPV type 16 prevalence in women with ASCUS of the uterine cervix.

BACKGROUND: Understanding racial influences on human papillomavirus (HPV) distribution in women with atypical squamous cells of undetermined significance (ASCUS) cytology via partial genotyping in a statewide population can inform HPV-based prevention efforts. METHODS: Women aged 21 to 65 years with any cytology result and partial HPV genotyping for ASCUS triage between January 1, 2014, and December 31, 2017, were included. All women attended a Mississippi State Department of Health clinic. Age, race, cytopathologic, and HPV data were extracted from the electronic health record and analyzed. Cytologic specimens were processed with ThinPrep and HPV testing with the Cobas 4800 assay. HPV genotypes were evaluated in hierarchical categories. Chi-square tests and multinomial logistic regression models evaluated associations between race and type prevalence. RESULTS: There were 43,106 women who underwent cervical cancer screening with cytology and ASCUS triage. Of these, 34,363 (80.2%) had normal cytology, 4672 (10.9%) had ASCUS, 2683 (6.3%) had a low-grade squamous intraepithelial lesion, and 633 (1.5%) had a high-grade squamous intraepithelial lesion. Blacks represented 69.3% of the sample and had a higher proportion of HPV-positive ASCUS (6.5%) in comparison with whites (5.6%). Blacks had significantly decreased odds of HPV-16 (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.6-0.9; P = .002) and significantly increased odds for 12 other types (OR, 1.37; 95% CI, 1.2-1.5; P < .0001) in comparison with whites. CONCLUSIONS: In a diverse population, significant differences in HPV genotypes are shown by race. Importantly, blacks with ASCUS are less likely to be positive for HPV-16 in comparison with whites. Ongoing work is evaluating the individual genotype prevalence and genotype-specific risk of precancer by race.

Precancerous cervical lesions and HPV genotypes identified in previously unsatisfactory cervical smear tests after inexpensive glacial acetic acid processing.

OBJECTIVE: To determine the effectiveness of using glacial acetic acid (GAA) to convert unsatisfactory bloody ThinPrep (TP) cervical smear test to satisfactory, and identify associated missed diagnoses and high-risk HPV (hrHPV) genotypes. METHODS: In a retrospective descriptive cross-sectional analysis, all TP tests performed in Mississippi, USA, 2012-2016, were evaluated for unsatisfactory results owing to blood. Tests that were converted to satisfactory by GAA treatment, and corresponding anomalies and HPV genotypes were identified. RESULTS: Among 106 384 TP tests, there were 1460 (1.37%) unsatisfactory results, of which 1442 (98.77%) were converted to satisfactory after GAA treatment. Laboratory preprocessing with GAA increased costs minimally. Precancerous lesions were detected in 166 (11.51%) of 1442 GAA-treated samples, of which 12 (7.2%) were high-grade lesions, 110 (66.3%) were atypical squamous cells of undetermined significance, and 63 (57.3%) tested positive for hrHPV. Of 60 genotyped samples, 39 (65%) had non-HPV16 and non-HPV18. Including mixed infections, 48 (80%) contained less-common hrHPV types, reflecting an unexpected distribution in bloody specimens. CONCLUSIONS: GAA pretreatment of bloody TP tests would reduce the incidence of unsatisfactory results and missed high-grade lesions, and prevent the cost of repeat tests and delayed treatment. Clinicians without access to GAA should consider HPV testing.