Sexual risk characteristics, social vulnerability, and anal cancer screening uptake among men living with HIV in the deep south.

ABSTRACTWithout standard guidelines, there is a critical need to examine anal cancer screening uptake in the South which has the highest HIV incidence in the U.S. We identified factors associated with screening among men living with HIV (MLHIV) at a large academic HIV outpatient clinic in Alabama. Relationships between sociodemographic, clinical, sexual risk characteristics and screening were examined using T-tests, Fisher's exact, Chi-square, and logistic regression analyses. Unadjusted and adjusted odds ratios (AOR) were computed to estimate the odds of screening. Among 1,114 men, 52% had received annual anal cytology (pap) screening. Men who were screened were more likely to have multiple sexual partners compared to men who were not screened (22.8% vs. 14.8%, p = 0.002). Among men with one partner, the youngest were almost five times more likely to be screened compared to middle-aged men (AOR = 4.93, 95% CI: 2.34-10.39). Heterosexual men had lower odds and men who reported unprotected anal sex had higher odds of screening. Our findings suggest a racial disparity, with older black MLHIV being the least likely to be screened. In the South, MLHIV who are older, black, heterosexual, or live in high social vulnerability counties may be less likely to receive annual anal cancer screening.

Human Papillomavirus Types and Cervical Cancer Screening among Female Sex Workers in Cameroon.

BACKGROUND: Female sex workers (FSWs) are at high risk for sexually transmitted infections (STIs), including infection with human papillomavirus (HPV) and cervical cancer due to occupational exposure. The objective of this study was to estimate the prevalence of HPV, HPV types, and precancerous lesions of the cervix among FSWs in Cameroon. MATERIAL AND METHODS: In this cross-sectional study, FSWs in Cameroon aged 30 years and above were screened for cervical cancer using high-risk HPV testing and genotyping and visual inspection with acetic acid and Lugol's iodine (VIA/VILI) enhanced using digital cervicography (DC) simultaneously. Those who were positive for VIA/VILI-DC were provided treatment with thermal ablation (TA) immediately for cryotherapy/TA-eligible lesions while lesions meeting the criteria for large loop excision of the transformation zone (LLETZ) were scheduled at an appropriate facility for the LLETZ procedure. HPV-positive FSWs without any visible lesion on VIA/VILI-DC were administered TA. Bivariate analyses were conducted to compare demographic and clinical characteristics. Crude and adjusted logistic regression models were computed for HPV infection status and treatment uptake as outcomes in separate models and their ORs and 95% confidence intervals (95% CI) were reported. RESULTS: Among the 599 FSWs aged 30 years and older that were screened for HPV and VIA/VILI-DC, 62.1% (95% CI: (0.58-0.66)) were positive for one or more HPV types. HPV type 51 had the highest prevalence (14%), followed by types 53 (12.4%) and 52 (12.2%). Type 18 had the lowest prevalence of 2.8% followed by type 16 with 5.2%. In the multivariable model, HIV-positive FSWs were 1.65 times more likely to be infected with HPV compared to their HIV-negative counterparts (AOR: 1.65, CI: 1.11-2.45). A total of 9.9% of the 599 FSWs were positive for VIA/VILI-DC. CONCLUSION: The prevalence of HPV infection among FSWs in Cameroon is higher than the worldwide pooled FSW prevalence. HPV types 51 and 53 were the most prevalent, while types 18 and 16 were the least prevalent. HIV status was the only variable that was significantly associated with infection with HPV.

Factors associated with adherence to post-treatment follow-up among a cohort of women with acetic acid/Lugol's iodine positive lesions of the cervix in Cameroon: A retrospective cohort study.

Background: Women treated for cervical precancerous lesions have up to a 30 % increased risk of developing cervical cancer compared to women in the general population. The aim of this study was to identify predictors for adherence to follow-up among women treated for precancerous lesions of the cervix in Cameroon. Materials and Methods: The study design was a retrospective cohort analysis of a five-year follow-up for women in Cameroon who were initially treated for cervical precancer lesions in 2013. Logistic regression models were used to determine factors associated with adherence to post-treatment follow-up. Statistical significance was set at p < 0.05. Results: Of the 344 women treated in 2013, 154 (44.77 %) never returned for a single post-treatment follow-up in five years. Marital status was the only variable statistically significantly associated with 5-year post-treatment follow-up adherence. women who had ever been married were 0.36 times (0.14 0.93)); p = 0. 0.035] less likely to adhere to post-treatment follow-up compared to women who have never been married. Although age was not statistically significant, women in the age group 30-49 years had some significance and they were 60 % [aOR, 95 %CI: 0.40 (0.18 0.89); p = 0.024] less likely to adhere to post-treatment follow-up when compared to women who were<30 years. Conclusion: Only about half of the women treated for cervical precancer in this cohort returned for post-treatment follow-up. Conducting needs assessments among these populations that are less likely to adhere to follow-up will allow us to implement and test strategies to improve adherence to follow-up.

Variations in Genes Encoding Human Papillomavirus Binding Receptors and Susceptibility to Cervical Precancer.

BACKGROUND: Cervical cancer oncogenesis starts with human papillomavirus (HPV) cell entry after binding to host cell surface receptors; however, the mechanism is not fully known. We examined polymorphisms in receptor genes hypothesized to be necessary for HPV cell entry and assessed their associations with clinical progression to precancer. METHODS: African American women (N = 1,728) from the MACS/WIHS Combined Cohort Study were included. Two case-control study designs were used-cases with histology-based precancer (CIN3+) and controls without; and cases with cytology-based precancer [high-grade squamous intraepithelial lesions (HSIL)] and controls without. SNPs in candidate genes (SDC1, SDC2, SDC3, SDC4, GPC1, GPC2, GPC3, GPC4, GPC5, GPC6, and ITGA6) were genotyped using an Illumina Omni2.5-quad beadchip. Logistic regression was used to assess the associations in all participants and by HPV genotypes, after adjusting for age, human immunodeficiency virus serostatus, CD4 T cells, and three principal components for ancestry. RESULTS: Minor alleles in SNPs rs77122854 (SDC3), rs73971695, rs79336862 (ITGA6), rs57528020, rs201337456, rs11987725 (SDC2), rs115880588, rs115738853, and rs9301825 (GPC5) were associated with increased odds of both CIN3+ and HSIL, whereas, rs35927186 (GPC5) was found to decrease the odds for both outcomes (P value ≤ 0.01). Among those infected with Alpha-9 HPV types, rs722377 (SDC3), rs16860468, rs2356798 (ITGA6), rs11987725 (SDC2), and rs3848051 (GPC5) were associated with increased odds of both precancer outcomes. CONCLUSIONS: Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical precancer progression. IMPACT: Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical precancer.

RNA-seq analysis identifies transcriptomic profiles associated with anal cancer recurrence among people living with HIV.

BACKGROUND: Chemoradiation therapy (CRT) is the standard of care for squamous cell carcinoma of the anus (SCCA), the most common type of anal cancer. However, approximately one fourth of patients still relapse after CRT. METHODS: We used RNA-sequencing technology to characterize coding and non-coding transcripts in tumor tissues from CRT-treated SCCA patients and compare them between 9 non-recurrent and 3 recurrent cases. RNA was extracted from FFPE tissues. Library preparations for RNA-sequencing were created using SMARTer Stranded Total RNA-Seq Kit. All libraries were pooled and sequenced on a NovaSeq 6000. Function and pathway enrichment analysis was performed with Metascape and enrichment of gene ontology (GO) was performed with Gene Set Enrichment Analysis (GSEA). RESULTS: There were 449 differentially expressed genes (DEGs) observed (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between the two groups. We identified a core of upregulated genes (IL4, CD40LG, ICAM2, HLA-I (HLA-A, HLA-C) and HLA-II (HLA-DQA1, HLA-DRB5) in the non-recurrent SCCA tissue enriching to the gene ontology term 'allograft rejection', which suggests a CD4+ T cell driven immune response. Conversely, in the recurrent tissues, keratin (KRT1, 10, 12, 20) and hedgehog signaling pathway (PTCH2) genes involved in 'Epidermis Development,', were significantly upregulated. We identified miR-4316, that inhibit tumor proliferation and migration by repressing vascular endothelial growth factors, as being upregulated in non-recurrent SCCA. On the contrary, lncRNA-SOX21-AS1, implicated in the progression of many other cancers, was also found to be more common in our recurrent compared to non-recurrent SCCA.Our study identified key host factors which may drive the recurrence of SCCA and warrants further studies to understand the mechanism and evaluate their potential use in personalized treatment.Key MessageOur study used RNA sequencing (RNA-seq) to identify pivotal factors in coding and non-coding transcripts which differentiate between patients at risk for recurrent anal cancer after treatment. There were 449 differentially expressed genes (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between 9 non-recurrent and 3 recurrent squamous cell carcinoma of anus (SCCA) tissues. The enrichment of genes related to allograft rejection was observed in the non-recurrent SCCA tissues, while the enrichment of genes related to epidermis development was positively linked with recurrent SCCA tissues.

How Accurate Is Oncologist Knowledge of Fertility Preservation Options, Cost, and Time in Female Adolescents and Young Adults?

Purpose: Often cited barriers to fertility preservation (FP) among female adolescent and young adult (AYA) cancer patients include cost and time. We hypothesized that oncologists overestimate the time and costs required for female FP. Methods: We distributed an electronic survey to physicians in oncology-related departments. The survey assessed the knowledge and utilization of gonadotoxic therapies, FP options and requirements, and FP referral patterns. Student's t, Fisher's exact, ANOVA, and Wilcoxon signed-rank tests were used for continuous variables as appropriate; the chi-squared test was used for categorical variables. Results: Among respondents who reported prescribing gonadotoxic agents to AYAs (n = 38), 79% reported often/always discussing FP options, while only half referred to a reproductive specialist often/always. A smaller proportion of pediatric oncologists discussed FP often/always (p = 0.04) and most referred <25% of patients to a reproductive specialist; however, the majority of other specialists referred ≥75% of patients to a reproductive specialist (p = 0.001). While most respondents accurately estimated the time required to complete FP, the majority overestimated the cost of an FP procedure. Knowledge of FP options was inconsistent, with 63.2% reporting that suppression of the hypothalamic-pituitary-ovarian-axis is an option for FP, with 82.6% of these classifying it as standard of care. Conclusions: With variation across specialties, most oncology specialists prescribing gonadotoxic therapies for AYA females discuss FP, while a smaller proportion refer patients for FP. Despite relative accuracy in estimating the time required for FP, they overestimate costs of FP. Educational curricula related to FP are necessary across oncology specialties, especially pediatric oncology.

Effect of misoprostol on type 3 transformation zone of the cervix among Cameroonian women.

Background: Type 3 transformation zone (TZ) of the cervix has been shown to be associated with a four to five-fold increased risk of missed precancerous/cancerous lesions. The aim of this study was to evaluate the effect of intravaginal misoprostol on the TZ among women with Type 3 TZ in Cameroon. Materials and methods: A single dose of vaginal misoprostol (400 mcg or 600 mcg) was administered as part of the plan of care for women with Type 3 TZ during cervical cancer screening. The primary outcome was successful conversion from Type 3 TZ to Types 1 or 2 TZ. Descriptive analysis was performed using chi-square and Fisher's exact tests. Results: Among the 90 of 107 (84.2%) women who returned for re-evaluation of the cervix, 43 (47.8%, 95% CI: 0.36%-0.60%) had conversion of Type 3 TZ to Types 1 or 2. Women who received misoprostol 600 mcg were more likely to have their Type 3 TZs converted to Types 1 or 2 than women receiving 400 mcg (p = 0.037). Conclusion: Misoprostol converted approximately 50% of Type 3 TZ to Types 1 or 2 in Cameroon. Misoprostol is feasible in converting Type 3 TZ to Types 1 or 2 among Cameroonian women.

Pathology findings among women with alterations in uterine bleeding patterns in cameroon.

PURPOSE: Endometrial cancer is on the rise in high-income countries but it has not been adequately studied in low-and-middle income countries especially in sub-Saharan Africa (SSA), likely due to scarce pathology facilities. The purpose of this study was to characterize and quantify the prevalence of endometrial hyperplasia or cancer in a cohort of women with abnormal uterine bleeding (AUB) who underwent endometrial biopsy in Cameroon. METHODS: We designed a cross-sectional study using medical records to characterize women who underwent endometrial biopsy in the Cameroon Baptist Convention Health Services (CBCHS) from 2008 to 2019. Pathologic diagnoses were classified as either endometrial hyperplasia, endometrial cancer, or no endometrial hyperplasia/cancer. We reported the overall prevalence of endometrial hyperplasia or cancer. Bivariate analyses compared patient characteristics between women with endometrial cancer, endometrial hyperplasia, and neither. RESULTS: The average age was 46.2 years and women had an average of 5.1 parity. We found that, 61 [(36.7% of 166 women; 95% CI (27.6-47.0%)] had endometrial hyperplasia or cancer. There were no cases of hyperplasia with atypia and 13 women had endometrial cancer. The remainder were comprised of benign or infectious pathologic findings. In bivariate analysis, mean ages were statistically different among the three groups (hyperplasia, cancer, and no hyperplasia/cancer), p < 0.001, and women with cancer had the highest age. Parity was statistically significantly different among the three groups (p = 0.002) and women with endometrial cancer had higher parity. CONCLUSION: We found that just over 1 in 3 women with AUB who underwent endometrial biopsy at a health system in SSA were found to have pathologic findings of endometrial hyperplasia or cancer, with no cases of hyperplasia with atypia. Women with endometrial cancer had higher mean age and parity.

Immunophenotype-associated gene signature in ductal breast tumors varies by receptor subtype, but the expression of individual signature genes remains consistent.

BACKGROUND: In silico deconvolution of invasive immune cell infiltration in bulk breast tumors helps characterize immunophenotype, expands treatment options, and influences survival endpoints. In this study, we identify the differential expression (DE) of the LM22 signature to classify immune-rich and -poor breast tumors and evaluate immune infiltration by receptor subtype and lymph node metastasis. METHODS: Using publicly available data, we applied the CIBERSORT algorithm to estimate immune cells infiltrating the tumor into immune-rich and immune-poor groups. We then tested the association of receptor subtype and nodal status with immune-rich/poor phenotype. We used DE to test individual signature genes and over-representation analysis for related pathways. RESULTS: CCL19 and CXCL9 expression differed between rich/poor signature groups regardless of subtype. Overexpression of CHI3L2 and FES was observed in triple negative breast cancers (TNBCs) relative to other subtypes in immune-rich tumors. Non-signature genes, LYZ, C1QB, CORO1A, EVI2B, GBP1, PSMB9, and CD52 were consistently overexpressed in immune-rich tumors, and SCUBE2 and GRIA2 were associated with immune-poor tumors. Immune-rich tumors had significant upregulation of genes/pathways while none were identified in immune-poor tumors. CONCLUSIONS: Overall, the proportion of immune-rich/poor tumors differed by subtype; however, a subset of 10 LM22 genes that marked immune-rich status remained the same across subtype. Non-LM22 genes differentially expressed between the phenotypes suggest that the biologic processes responsible for immune-poor phenotype are not yet well characterized.

A 12-year retrospective evaluation of anal pre-cancerous lesions and cancer in people living with HIV-1 infection in the Southeastern U.S.

BACKGROUND: Anal cancer is rare in the general population in both genders in the US, but an increased incidence of anal cáncer (AC) has been reported among people living with HIV-1 infection (PLWH) and little is known among the population in South US. METHODS: In a retrospective study design, electronic health records from 2006 to 2018 were reviewed in a HIV clinical cohort at the University of Alabama at Birmingham. Associations of demographic, sociodemographic, and HIV-clinical indicators were examined in univariate analyses between high-grade squamous intraepithelial lesions (HSIL) and AC cases and condition-free individuals. Factors for anal/rectal cytology screening tests among PLWH were also assessed over time. Ages at onset of anal cancer were compared with the general US population reported by the National Surveillance, Epidemiology, and End Results Program. RESULTS: A total of 79 anal HSIL (96% men) and 43 cancer (100% men) patients were observed along with 4367 HSIL/cancer-free patients (75.9% men). HSIL (P < 0.0001) and AC (0.0001 < P < 0.01) were associated with being men who have sex with men (MSM). An incidence of 258 per 100,000 person-year was observed among this clinical cohort of PLWH. PLWH who were 45-54 years appeared to be at highest risk of AC (58.1%), as compared to those 55-64 years in the general population. Overall, 79% of PLWH anal cancers were diagnosed among those under 55 years (vs 39.5% in general population) indicating early onset of AC. In total 29.1% of HSIL and 44.2% of AC patients had not received an anal/rectal cytology examination 1 year prior to diagnosis. CONCLUSION: AC incidence among HIV-infected men was 161 times higher than general population with an earlier age of onset/diagnosis. Many patients with AC had missed screening opportunities that could potentially have captured neoplasia in pre-cancerous stages. AC-related screening guidelines need to be integrated into routine clinical care, especially among PLWH at highest risk such as MSM and those with lower CD4 counts.

CD4 Trajectory Models and Onset of Non-AIDS-Defining Anal Genital Warts, Precancer, and Cancer in People Living With HIV Infection-1.

BACKGROUND: It is unclear how the characteristics of CD4 counts predict non-AIDS-defining human papillomavirus-related anogenital warts (AGWs) and anal high-grade squamous intraepithelial lesions/cancer (HSIL) in people living with HIV infection-1 (PLWH). We compared the associations between 3 CD4 counts measures and these disease outcomes in the study. METHODS: Retrospective sociobehavioral and clinical data from electronic health records of 4803 PLWH from 2006 to 2018 were included. Three different measurements of CD4 counts-(a) nadir, (b) median, and (c) trajectory-were estimated. Six CD4 trajectory groups were constructed using the group-based trajectory modeling from all patients older than 18 years with ≥3 clinical visits. Univariate and multivariable logistic regression models were used to assess the associations with AGW and HSIL, separately. RESULTS: A total of 408 AGW, 102 anal HSIL (43 HSIL, 59 cancer), 4 penile cancer, and 15 vaginal cancer cases were observed. Median CD4 (<200 cell/µL) was associated with AGW (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.6-3.0]), and anal HSIL (OR, 2.7 [95% CI, 1.5-5.0]; each, P < 0.001). Low nadir CD4 (<200 cell/µL) was associated with AGW (OR, 1.8 [95% CI, 1.3-2.6]) and anal HSIL (OR, 2.4 [95% CI, 1.2-4.7]; each, P ≤ 0.001). Different patterns (declining and sustained low CD4 counts) of CD4 trajectories showed the strongest associations with onset of both AGW (OR, 1.8-3.1) and HSIL (OR, 2.7-6.7). CONCLUSIONS: People living with HIV infection-1 with the same median CD4 could have very different CD4 trajectories, implying different dynamics of immune status. CD4 trajectory could be a better predictor of incident AGW and HSIL among PLWH.

Geographical and Racial Disparities in Head and Neck Cancer Diagnosis in South-Eastern United States: Using Real-World Electronic Medical Records Data.

Background: Rurality, race, and age at diagnosis are important predictors in head and neck cancer (HNC) prognosis. However, literature on the associations of rurality and race with age at HNC diagnosis is limited. Data on geographical, racial, and gender disparities in young HNC patients (diagnosed ≤45 years) are also scarce. Materials and Methods: This retrospective study assesses rural-urban, racial, and gender disparities in age at HNC diagnosis, using electronic medical records (Cerner) data of 4258 HNC patients (1538 residing in rural counties and 2720 in urban counties) from National Cancer Institute-designated cancer center in Alabama. Rurality was defined based on 2010 U.S. Census Bureau's rural-urban classification. Logistic regression was used to assess the association of young HNC diagnosis with demographical, behavioral, and clinical variables. ArcGIS 10.2 was used to map geospatial distribution of age and population-adjusted HNC case across rural and urban counties. Results: Patients from rural counties were less likely to be diagnosed at younger age (≤45 years) compared with urban counties (odds ratio [OR] [95% confidence interval (CI)]: 0.74 [0.58-0.93]). Most patients present at stage III/IV (64.9% in rural and 60.2% in urban). Compared with white patients, black patients were 70% more likely to get diagnosed at a young age (95% CI: 1.23-2.35). Young patients were more likely to be females and blacks compared with older patients (p<0.0001). Among oral cavity cancer patients, rural patients were 51% less likely to get diagnosed at young age compared with urban patients (95% CI: 0.27-0.89). Conclusions: Head and neck cancer screening is not routinely conducted so most show up at later stage of cancer. There is also evidence of disparities in age at HNC diagnosis based on rurality, race, and gender; targeted screening can help in reducing these disparities.

Comorbidities associated with HPV infection among people living with HIV-1 in the southeastern US: a retrospective clinical cohort study.

BACKGROUND: The southeastern US is an epicenter for incident HIV in the US with high prevalence of human papillomavirus (HPV) co-infections. However, epidemiologies of HPV-associated clinical conditions (CC) among people living with HIV-1 infection (PLWH) are not fully known. METHODS: Electronic medical records (EMR) of PLWH attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analyzed. The retrospective study was nested within the University of Alabama at Birmingham HIV clinical cohort, which has electronically collected over 7000 PLWH's clinical and sociobehavioral data since 1999. Incidence rates of HPV-related CC including anogenital warts, penile, anal, cervical, and vaginal/vulvar low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) were estimated per 10,000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of incident CC. All rates and trends were stratified by gender and race. RESULTS: Of the 4484 PLWH included in the study (3429 men, 1031 women, and 24 transgender), we observed 1038 patients with HPV-related CC. The median nadir CD4 count (cells/uL) was higher in the HPV-condition free group than the case groups (P < 0.0001). Anogenital warts, anal LSIL, HSIL, and cancer were more likely to be diagnosed among HIV-infected men than women. White men presented more frequently with anal LSIL and anal and penile cancers than black men (P < 0.03). White women were also more likely to be diagnosed with cervical HSIL (P = 0.023) and cancer (P = 0.037) than black women. CONCLUSIONS: There were significant differences between gender and race with incidence of HPV-related CC among HIV patients. EMR-based studies provide insights on understudied HPV-related anogenital conditions in PLWH; however, large-scale studies in other regions are needed to generalize current findings and draw public health attention to co-infection induced non-AIDS defining comorbidities among PLWH.

Variants in immune-related genes and genital HPV 16 persistence in men.

OBJECTIVES: While most human papillomavirus (HPV) infection clears on its own, persistent HPV infection can cause genital warts and anal, penile and oropharyngeal cancers in men. We conducted genetic analysis in a sub-cohort of the HPV infection in men (HIM) study to test the hypothesis that differences in host genes influence HPV persistence in men. METHODS: Baseline and longitudinal genital HPV status at the genitals was measured every 6-months using the Linear Array assay amplified HPV L1 gene fragment using the PGMY09/11 L1 consensus primer system. DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) in the customized genome-wide genotyping array, the "TxArray," were examined using logistic regression in a case-control study design to assess the association with HPV16 persistence/clearance. RESULTS: Of the total of 737,742 autosomal SNPs in the array, 605,885 passed basic quality control and were examined between 40 men (cases) with > 18 months persistent genital HPV 16 infection vs. 151 controls who were HPV 16-positive, but whose infections cleared in < 18 months. The logistic regression analysis from this case-control study showed variants in several gene regions associated with genital HPV 16 persistence, with the strongest association detected with SNPs on chromosomes 20 (p < 5.72 × 10-6) and 15 (p < 5.89 × 10-6), after adjusting for age, smoking status, number of sex partners and four principal components (ancestral background). CONCLUSIONS: Our results provide a preliminary basis for understanding the biological mechanism of oncogenic HPV 16 pathogenesis at the genitals in men. Some of the genes flanking the top hit SNPs are consistent with previous findings in both HPV related and non-related cancers but further genetic studies in larger cohorts are warranted to confirm these and identify novel major susceptibility genes involved in the pathogenesis of genital HPV persistence in men.