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PURPOSE Squamous cell carcinoma of the anus (SCCA) incidence and mortality rates are rising in the United States. Understanding state-level incidence and mortality patterns and associations with smoking and AIDS prevalence (key risk factors) could help unravel disparities and provide etiologic clues. METHODS Using the US Cancer Statistics and the National Center for Health Statistics data sets, we estimated state-level SCCA incidence and mortality rates. Rate ratios (RRs) were calculated to compare incidence and mortality in 2014-2018 versus 2001-2005. The correlations between SCCA incidence with current smoking (from the Behavioral Risk Factor Surveillance System) and AIDS (from the HIV Surveillance system) prevalence were evaluated using Spearman's rank correlation coefficient. RESULTS Nationally, SCCA incidence and mortality rates (per 100,000) increased among men (incidence, 2.29-3.36, mortality, 0.46-0.74) and women (incidence, 3.88-6.30, mortality, 0.65-1.02) age ≥ 50 years, but decreased among men age < 50 years and were stable among similar-aged women. In state-level analysis, a marked increase in incidence (≥ 1.5-fold for men and ≥ two-fold for women) and mortality (≥ two-fold) for persons age ≥ 50 years was largely concentrated in the Midwestern and Southeastern states. State-level SCCA incidence rates in recent years (2014-2018) among men were correlated ( r = 0.47, P < .001) with state-level AIDS prevalence patterns. For women, a correlation was observed between state-level SCCA incidence rates and smoking prevalence ( r = 0.49, P < .001). CONCLUSION During 2001-2005 to 2014-2018, SCCA incidence and mortality nearly doubled among men and women age ≥ 50 years living in Midwest and Southeast. State variation in AIDS and smoking patterns may explain variation in SCCA incidence. Improved and targeted prevention is needed to combat the rise in SCCA incidence and mitigate magnifying geographic disparities. [Media: see text]

Cervical cancer incidence is rising in Puerto Rico (PR). Screening for cervical cancer could prevent the occurrence of the disease or lead to its early detection, translating to survival benefits. In this study, we evaluated the association of cervical cancer screening status with tumor diagnosis and survival among Hispanic women living in PR.We analyzed data for 506 incident cases of primary cervical cancer diagnosed from the period 2011-2014, identified through the PR Central Cancer Registry. We ascertained screening status 3 years before cervical cancer diagnosis using data from the period 2008-2014 from the PR Central Cancer Registry-Health Insurance Linkage Database. Patients were followed until 2019. Our outcomes of interest were stage at diagnosis and survival.Most women (78.86%) were covered by public insurance (Medicare and/or Medicaid), and 69.57% underwent screening 3 years before their diagnosis. The proportion of cases diagnosed with localized stage was significantly greater among the screened group compared with those unscreened (43.5% vs 33.1%, p.0001). Multivariate analysis showed that women insured through Medicaid were less likely to have been screened when compared with women with private insurance (odds ratio = 0.29; 95% CI = 0.16-0.52). Five-year survival was significantly greater among screened (72%) than unscreened (54%) women (plog-rank0.05). The multivariate Cox proportional hazards model showed that women who received screening had a 39% (hazard ratio [HR] = 0.61; 95% CI = 0.43-0.87) lower risk of death compared with unscreened women.Our findings exemplify survival benefits among women who underwent cervical cancer screening in PR. Interventions to improve screening uptake and adherence are a public health priority.

Background Men who have sex with men (MSM) without HIV are known to be at elevated relative risk for Human papillomavirus (HPV)-associated anal cancer in comparison to men who have sex with women (MSW), but are poorly characterized in terms of anal cancer incidence due to absence of reporting of sexual behavior/identity at a population-level. Methods By combining age-specific statistics from multiple data sources (anal cancer incidence among all males; anal cancer incidence among MSM and MSW living with HIV; population size of men living with HIV by sexual orientation), we developed a mathematical model to estimate anal cancer incidence, annual number of cases, and proportion by (a) sexual orientation (MSM versus MSW), (b) HIV status, and (c) age ( Results Anal cancer incidence (per 100 000) among MSM without HIV was 1.4 (95% uncertainty interval [UI], 0.6 to 2.3), 17.6 (95% UI = 13.8–23.5), and 33.9 (95% UI = 28.3–42.3), at ages 30–44, 45–59 and ≥60 years, respectively. 19.1% of all male anal cancer occurred in MSM without HIV, increasing from 4% of anal cancer diagnosed at 30–44 years to 24% at ≥60 years; 54.3% occurred in MSW without HIV (increasing from 13% at age 30–44 to 67% at >60 years), and the remaining 26.6% in men (MSM and MSW combined) living with HIV (decreasing from 83% at age 30–44 to 9% at >60 years). Conclusions These findings should inform anal cancer prevention recommendations in male risk groups, including, for the first time, for the important group of MSM without HIV.

Background: Home-based self-sampling for human papillomavirus (HPV) testing may be an alternative for women not attending clinic-based cervical cancer screening. Methods: We assessed barriers to care and motivators to use at-home HPV self-sampling kits during the COVID-19 pandemic as part of a randomized controlled trial evaluating kit effectiveness. Participants were women aged 30-65 and under-screened for cervical cancer in a safety-net healthcare system. We conducted telephone surveys in English/Spanish among a subgroup of trial participants, assessed differences between groups, and determined statistical significance at pResults: Over half of 233 survey participants reported that clinic-based screening (Pap) is uncomfortable (67.8%), embarrassing (52.4%), and discomfort seeing male providers (63.1%). The last two factors were significantly more prevalent among Spanish versus English speakers (66.4% vs. 30% (p=0.000) and 69.9 vs. 52.2% (p=0.006), respectively). Most women who completed the kit found Pap more embarrassing (69.3%), stressful (55.6%), and less convenient (55.6%) than the kit. The first factor was more prevalent among Spanish versus English speakers (79.6% vs. 53.38%, p=0.001) and among patients with elementary education or below. Conclusions: The COVID-19 pandemic influenced most (59.5%) to participate in the trial due to fear of COVID, difficulty making appointments, and ease of using kits. HPV self-sampling kits may reduce barriers among under-screened women in a safety-net system. Funding: This study is supported by a grant from the National Institute for Minority Health and Health Disparities (NIMHD, R01MD013715, PI: JR Montealegre). Clinical trial number: NCT03898167.

Despite the overall national decline in Kaposi sarcoma (KS) incidence in the United States among persons living with HIV, previous studies suggest there might be specific subgroups of the US population that are associated with higher KS incidence rates than others. Using the 2001-2018 National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program database, we assessed KS incidence trends among young men aged 20-34 years by race and ethnicity and geographic region. Statistical significance is 2-sided. The KS incidence rate increased nationally by 1.5% per year in non-Hispanic Black men, whereas the rate decreased statistically significantly by 3.5% per year in non-Hispanic White men. A statistically significant 3.3% per year increase among young non-Hispanic Black men in the South and no change among those living in non-South regions were observed. Targeted HIV prevention and treatment in young non-Hispanic Black men in the South and further research addressing the increased KS incidence and burden in this vulnerable population are needed.

The objective of our study was to describe oral and genital human papillomavirus (HPV) infection prevalence and concordance by sexual orientation among US men using a nationally representative sample. We conducted a retrospective cross-sectional analysis of the 2013-2016 National Health and Nutrition Examination Survey. The survey conducts a physical examination and collects oral rinse and genital swab specimens; demographic and health behaviors are self-reported. We used descriptive statistics and multivariate regression models to estimate HPV infection prevalence and the likelihood of HPV infection, respectively. All analyses were adjusted for National Health and Nutrition Examination Survey design and weights, and statistical significance was tested at a 2-sided P value of less than .05. Men who have sex with men had a statistically significantly higher prevalence of oral HPV (high-risk, 9-valent, 4-valent, and HPV 16 and 18), genital HPV (9-valent, 4-valent, and HPV 16 and 18), and concordant oral and genital HPV (high-risk and 9-valent) infections compared with heterosexual men. Improved HPV prevention among men is needed.

Squamous cell carcinoma of the anus (SCCA) is caused by HPV, and is elevated in persons living with HIV (PLWHIV). We aimed to estimate sex- and HIV-stratified SCCA burden at a country, regional and global level. Using anal cancer incidence estimates from 185 countries available through GLOBOCAN 2020, and region/country-specific proportions of SCCA vs non-SCCA from the Cancer Incidence in Five Continents (CI5) Volume XI database, we estimated country- and sex-specific SCCA incidence. Proportions of SCCA diagnosed in PLWHIV, and attributable to HIV, were calculated using estimates of HIV prevalence (UNAIDS 2019) and relative risk applied to SCCA incidence. Of 30 416 SCCA estimated globally in 2020, two-thirds occurred in women (19 792) and one-third among men (10 624). Fifty-three percent of male SCCA and 65% of female SCCA occurred in countries with a very high Human Development Index (HDI). Twenty-one percent of the global male SCCA burden occurred in PLWHIV (n = 2203), largely concentrated in North America, Europe and Africa. While, only 3% of global female SCCA burden (n = 561) occurred in PLWHIV, mainly in Africa. The global age-standardized incidence rate of HIV-negative SCCA was higher in women (0.55 cases per 100 000) than men (0.28), whereas HIV-positive SCCA was higher in men (0.07) than women (0.02). HIV prevalence reached40% in 22 countries for male SCCA and in 10 countries for female SCCA, mostly in Africa. Understanding global SCCA burden by HIV status can inform SCCA prevention programs (through HPV vaccination, screening and HIV control) and help raise awareness to combat the disease.

BACKGROUND Anal cancer disproportionately affects people with HIV (PWH). High-grade squamous intraepithelial lesions (HSIL) are cancer precursors and treating them might prevent anal cancer. Data on adherence to HSIL treatment and surveillance is limited but needed to identify deficiencies of screening strategies. METHODS We collected data on high-resolution anoscopy (HRA) attendance and outcomes from 2009 to 2019 in a large urban anal cancer-screening program. Patients with an initial HSIL diagnosis were followed for return for HSIL electrocautery ablation within 6 months of index HSIL diagnosis, and follow-up HRA within 18 months of index HSIL diagnosis. We also evaluated predictors of these outcomes in univariable and multivariable analyses. RESULTS One thousand one hundred and seventy-nine unique patients with an anal HSIL diagnosis were identified and 684 (58%) returned for electrocautery ablation. Of those treated, only 174 (25%) and only 9% of untreated HSIL patients (47 of 495) underwent surveillance HRA within 18 months of index HSIL diagnosis. In multivariable analyses, black patients and PWH regardless of virologic control were less likely to undergo HSIL ablation within 6 months of HSIL diagnosis whereas patients with commercial insurance were more likely to be treated within 6 months of diagnosis. Among treated HSIL patients, PWH with viremia had a lower likelihood of engaging in post-treatment surveillance within 18 months of HSIL diagnosis. DISCUSSION Even in large specialized anal cancer screening programs adherence to HSIL treatment and surveillance is low. Psychosocial and economic determinants of health may impact retention in care. Addressing both personal and structural barriers to patient engagement may improve the effectiveness of anal cancer screening.

Introduction: Anal cancer (AC) risk is greatly elevated among persons living with HIV (PLWH), particularly men who have sex with men (MSM). The incidence of anal cancer among PLWH in Puerto Rico is 60.5 per 100,000 in MSM. Smoking and sexual behaviors may enhance anal cancer risk among PLWH. Therefore, we describe the prevalence of risk factors for AC, overall and by sexual risk group (MSM, women, and men who have sex with women [MSW]). We also evaluated receipt of cancer preventive strategies: HPV vaccination and AC screening, among a sample of PLWH in Puerto Rico. Methods: A cross-sectional study was conducted (Sept 2020 - Dec 2021) among PLWH ≥26 aged in Puerto Rico (n=212). Participants answered a phone interview that collected information on relevant characteristics. AC risk factors evaluated were current smoking, age of sexual initiation (≤15 years), lifetime anal sex, 10 or more lifetime sexual partners, history of AIDS, genital warts, and HPV infection. HPV vaccination and AC screening status were also evaluated. The overall and sexual risk group specific prevalence of AC risk factors and preventive behaviors were described. In addition, the prevalence ratio (PR) of the variables of interest, comparing the sexual risk groups, was estimated with 95% confidence intervals using Poisson regression. Results: Mean age of participants was 52.8 ± (SD=10.2); 44.1% were MSM, 23.2% were MSW, and 32.7% were women. Most PLWH had public health insurance (84.4%), an education level of high-school or less (45.7%), and 9.5% had a history of intravenous drug use. Regarding the prevalence of AC risk factors, 58.3% had 10 or more lifetime sex partners, 51% had their first sexual relationship at age ≤15 years, 29.3% were current smokers, and 75.8% of women had history of anal sex. In addition, 20.8% reported being diagnosed with AIDS, 16.5% had a history of genital warts, and 12.0% had HPV infection. Only 7.5% reported HPV vaccination and 52.2% reported ever having had an anal pap test. MSM had the highest prevalence of risky sexual behaviors, although no statistical difference was seen in the PRs. For preventive strategies, women (PR: 3.13, 95% CI 1.52-6.46) and MSM (PR: 3.42, 95% CI 1.70-6.90) had higher prevalence of anal pap uptake than MSW. Conclusion: Persons living with HIV in Puerto Rico had high prevalence of current smoking use and risky sexual behavior. Despite their increased risk of AC, and only over half had been screened for AC. Continued education and awareness about AC risk factors, smoking cessation, and importance of prevention strategies are important among PLWH. Citation Format: Sandra I. Garcia-Camacho, Jeslie M. Ramos-Cartagena, Marievelisse Soto-Salgado, Vivian Colon-Lopez, Karen J. Ortiz-Ortiz, Ashish A. Deshmukh, Ana P. Ortiz. Anal cancer risk factors and utilization of cancer preventive strategies in people living with HIV in Puerto Rico. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4179.

Background Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. Herein, we compare anal cytology to hrHPV DNA testing and 2 novel cytology/hrHPV cotesting algorithms among 3 high-risk populations. Methods Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1837 participants (1504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women). Performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between 4 strategies with distinct HRA referral thresholds: cytology (atypical squamous cells of undetermined significance, ASCUS); hrHPV testing (any hrHPV positive); algorithm A (benign cytology/HPV16/18 positive or ASCUS/hrHPV positive); and algorithm B (benign or ASCUS/hrHPV positive). Results Histological HSIL/cancer was detected in 756 (41%) participants. Cytology had the lowest sensitivity (0.76–0.89) but highest specificity (0.33–0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies/subgroups (range, 0.16–0.36). Conclusions Screening algorithms that incorporate cytology and hrHPV testing significantly increased sensitivity but decreased specificity to detect anal precancer/cancer among high-risk populations.

To inform optimal approaches for detecting anal precancers, we performed a systematic review and meta-analysis of the diagnostic accuracy of anal cancer screening tests in different populations with elevated risk for anal cancer. We conducted a literature search of studies evaluating tests for anal precancer and cancer (anal intraepithelial neoplasia grade 2 or worse, AIN2+) published between January 1, 1997 to September 30, 2021 in PubMed and Embase. Titles and abstracts were screened for inclusion and included articles underwent full-text review, data abstraction and quality assessment. We estimated the prevalence of AIN2+ and calculated summary estimates and 95% confidence intervals (CI) of test positivity, sensitivity and specificity and predictive values of various testing strategies, overall and among population subgroups. A total of 39 articles were included. The prevalence of AIN2+ was 20% (95% CI, 17-29%), and ranged from 22% in men who have sex with men (MSM) living with HIV to 13% in women and 12% in MSM without HIV. The sensitivity and specificity of cytology and HPV testing were 81% and 62% and 92% and 42%, respectively, and 93% and 33%, respectively for cytology and HPV co-testing. AIN2+ risks were similar among those testing positive for cytology, HPV, or co-testing. Limited data on other biomarkers (HPV E6/E7 mRNA and p16/Ki-67 dual stain), suggested higher specificity, but lower sensitivity compared with anal cytology and HPV. Our findings provide important evidence for the development of clinical guidelines using anal cytology and HPV testing for anal cancer screening.

Background Hormesis is an adaptive response of a biological system to low dose of stressors. It exerts beneficial effects to enable the cells and organisms to sustain the unfavourable conditions. Mild heat stress is one of the widely studied hormetic agents having antiageing and lifespan prolonging effects. In order to study the effect of mild heat stress on the primary culture of mouse prefrontal cerebrocortical neurons with reference to ageing-associated degenerative alterations the present investigations were carried out. Study design The prefrontal cerebrocortical neurons of E17 day mouse embryo were cultured on poly-l-lysine coated coverslips and fed with neurobasal medium supplemented with B-27 at 37 °C and 5% CO2. The neurons were divided into two groups: control group and mild heat stress group. The neurons from the control group were incubated at 37 °C without any heat stress. The neurons from the mild heat stress group were subjected to hyperthermic stress of 38 °C for 30 min on 2nd, 4th and 6th day of seeding. Methods On the 3rd, 5th and 7th day of incubation, viability was studied by calcein-AM and propidium iodide assay and cell death assay was carried out by lactate dehydrogenase (LDH) assay. The surviving neurons were enumerated on 10th, 15th and 20th day of incubation by live cell imaging. All microscopic studies were carried out by observer blinding. Results It was observed that there was higher percentage of viable neurons and lower percentage of degenerating neurons in the mild heat stress group than the control. The difference was highly significant (p < 0.001). Conclusion Mild heat stress (38 °C for 30 min on every alternate day up to 6 days of incubation) exerts hormetic effects on the primary culture of mouse prefrontal cerebrocortical neurons by delaying the degenerative alterations.

Background Women living with HIV (WLHIV) have a high risk of developing invasive anal cancer. Anal cancer may be prevented with early detection and treatment of anal histologic high-grade squamous intraepithelial lesions (HSIL). However, there are limited data on the efficacy of anal HSIL treatment in WLHIV. Study design We conducted a retrospective study of WLHIV treated for anal HSIL under high-resolution anoscopy (HRA) guidance from January 1, 2007 to December 31, 2017 with at least one post-treatment visit at an urban tertiary care hospital. Results Forty-five WLHIV women with at least 1 follow-up evaluation after treatment for anal HSIL were identified. The median age was 46 years (range 35-66 years), 63% were African American, 27% were Hispanic/Latino, and 53% were current smokers. The mean absolute CD4 T-cell count was 516 cells/mm; 50% and 24% of the cohort had a history of cervical or vulvar HSIL respectively. The cumulative probability of anal HSIL recurrence was 29% at 12 months, 52% at 24 months, and 79% at 36 months post-treatment. Conclusion Most WLHIV treated for anal HSIL recurred within 3 years, suggesting need for continued surveillance after treatment. Our data contribute to the information needed to develop effective anal cancer prevention guidelines in WLHIV.

Background Electrocautery ablation (EA) is a common treatment modality for patients with anal high-grade squamous intraepithelial lesions (HSILs), but to the authors' knowledge its effectiveness has been understudied. The objective of the current study was to determine ablation outcomes and to identify clinicopathological factors associated with postablation disease recurrence. Methods A total of 330 people living with HIV with de novo intra-anal HSIL who were treated with EA from 2009 to 2016 were studied retrospectively. Using long-term, surveillance high-resolution anoscopy biopsy data, treatment failures were classified as local recurrence (HSIL noted at the treated site at the time of surveillance) or overall recurrence (HSIL noted at treated or untreated sites). The associations between these outcomes and clinical factors were analyzed using Cox proportional hazards models. Results Approximately 88% of participants were men who have sex with men. The median age of study participants was 45.5 years (range, 35-51 years) and approximately 49% had multiple index HSILs (range, 2-6 index HSILs). At a median of 12.2 months postablation (range, 6.3-20.9 months postablation), approximately 45% of participants had developed local recurrence whereas 60% had developed overall recurrence. Current cigarette smoking, HIV viremia (HIV-1 RNA ≥100 copies/mL), and multiple index HSILs were found to be predictive of local recurrence. Overall recurrence was more common in current smokers and those with multiple index lesions. In multivariable models that included human papillomavirus (HPV) genotypes, baseline and persistent infections with HPV-16 and/or HPV-18 were found to be significantly associated with both local and overall recurrence. Conclusions EA is an effective treatment modality for anal HSIL in people living with HIV, but rates of disease recurrence are substantial. Multiple index HSILs, HIV viremia, current cigarette smoking, and both baseline and persistent infection with HPV-16 and/or HPV-18 appear to negatively impact treatment success. Ongoing surveillance is imperative to capture recurrence early and improve long-term treatment outcomes.

Background: Squamous cell carcinoma of the anus (SCCA), caused by human papillomavirus infection (HPV), is the most frequently diagnosed form of anal cancer (85%-90%). SCCA incidence has increased dramatically among the general population in Puerto Rico (nearly 5% annually) and the risk is disproportionately elevated among patients living with HIV. SCCA is preventable through HPV vaccination and screening. Therefore, the study of the cost of anal cancer care could have significant implications for understanding preventable economic burden in Puerto Rico. Objective: Determine the lifetime and phase-specific cost of SCCA cases aged ≥21 diagnosed during 2009-2016 in Puerto Rico. Method: This population-based study used the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database (PRCCR-HILD), which links PRCCR data with health insurance claim data from the principal health insurance companies and the government health plan. PRCCR-HILD has information for almost 90% of Puerto Rico's cancer cases from 2008. We matched SCCA cases and non-cancer control (1:1) by age and sex for each phase of care (initial, continuation, and terminal). SCCA-related costs were calculated by subtracting the costs between SCCA patients and the control group. We used the phase-specific monthly cost estimates combined with survival data, stratified by age and cancer stage (localized, regional, and distance), to calculate the lifetime and average annual cost (discount at 3%) for SCCA. The cost was adjusted to 2019 US dollars using the consumer price index. We used the number of SCCA incident cases for 2019, stratified by age group and multiplied by the lifetime SCCA cost estimates, to calculate the SCCA-related lifetime economic burden for Puerto Rico. Results: Of the 351 patients with SCCA included in this study, the mean age at diagnosis was 64 years, 66.4% were women, 57.6% were diagnosed at a localized stage, and 23.1% were enrolled in private insurance. The overall survival after cancer diagnosis was 18 years. Meanwhile, the average monthly costs per patient were higher in the initial phase ($4,755), followed by the terminal phase ($3,499). The main cost driver in all phases was the outpatient costs. However, inpatient costs increased substantially at the terminal phase of care. The average lifetime cost for patient with SCCA was $137,343 (95% CI: $130,873-$145,241) (2019 US dollars). The average SCCA per year cost was $9,193 (95% CI: $8,744-$9,895), while the SCCA-related lifetime economic burden for 2018 in Puerto Rico was nearly $8.7 million. Conclusion: To our knowledge, this is the first study to describe the cost of SCCA management in Puerto Rico. Although SCCA continues to be relatively rare among the general population, our study shows that the SCCA-related lifetime economic burden is substantial and could continue to rise due to the rising SCCA burden in Puerto Rico. These findings could support the evaluation of the impact of strategies to reduce the SCCA burden through HPV vaccination and anal cancer screening for high-risk populations. Citation Format: Karen J. Ortiz-Ortiz, Axel Gierbolini-Bermúdez, Ana P. Ortiz, Karen Pabón-Cruz, Chi-Fang Wu, Jeslie Ramos-Cartagena, Reydi Morales-Martínez, Ashish A. Deshmukh. Lifetime cost of care associated with squamous cell carcinoma of the anus in Puerto Rico [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A052.

Oropharyngeal cancer (OPC) incidence is rising among men in the US. Comprehensive assessments of nationwide trends in OPC incidence and mortality by demographics, tumor characteristics at diagnosis, and geography are lacking.We examined secular trends in OPC incidence and mortality rates in all 50 US states and the District of Columbia (DC).In this cross-sectional study, we used the US Cancer Statistics data set to examine OPC incidence trends from 2001 through 2017. Observed and incidence-based mortality trends were evaluated using data from the National Center for Health Statistics and Surveillance Epidemiology and End Results program, respectively. Data analysis was conducted from January to April 2021.Nationwide, 260 182 OPC cases were identified; 209 297 (80%) occurred in men, 168 674 (65%) with regional stage, and 142 068 (55%) in the Southeast and Midwest regions, during 2001 to 2017. Incidence of OPC increased nationally 2.7% per year among men, with a notable (over 3% per year) rise among non-Hispanic White men and in men aged 65 years and older. Overall, among women, the annual percentage change was 0.5% (95% CI, -0.28% to 1.22%). Among men, with a 3.1% per year rise (95% CI, 2.4% to 3.8%), regional-stage OPC incidence increased nearly 2-fold. Among women, regional-stage OPC incidence increased 1.0% per year (95% CI, 0.3% to 1.7%). Among men, OPC incidence increased in all states and regions except Alaska, DC, and Wyoming. Among men, the most pronounced increases (more than 3.5% per year) were clustered in the Southeast and Midwest regions. Among women, a rise of more than 2% per year was also concentrated in the Southeast and Midwest regions. Among men, OPC incidence-based mortality increased 2.1% per year (95% CI, 1.0% to 3.2%) overall in recent years (from 2006 to 2017). In contrast, among women, the annual percentage change in OPC incidence-based mortality was -1.2% (95% CI, -2.5% to 0.1%).The findings of this cross-sectional study suggest that the incidence of OPC has continued to increase nationally among men in the US, with rapid increases among the elderly population. The notable rise in regional-stage OPC and the concurrent recent rise in mortality among men is troubling and calls for urgent improvements in prevention. Distinct geographic patterns with notable rises in the Midwest and Southeast regions imply the need for improved and targeted prevention as well as future studies to understand etiological reasons for geographic disparities.

The Centers for Disease Control and Prevention (CDC) promotes taking a 'bundling approach' (i.e., administering Tetanus, diphtheria toxoids, and acellular pertussis [Tdap] and human papillomavirus [HPV] vaccines in the same way and on the same day) for adolescent vaccinations. Recent trends and patterns in Tdap-HPV vaccination bundling in the USA remain undocumented. In addition, the implications of bundling Tdap-HPV vaccination for HPV vaccine series completion remain unknown. To address these critical knowledge gaps, we performed a retrospective study using a nationwide sample of privately insured adolescents (Optum's de-identified Clinformatics® Data Mart Database). Tdap-HPV vaccination bundling (per 100 Tdap vaccination encounters) during 2014-2018 was estimated overall, for 50 states, and by adolescents' age, sex, and provider specialties. Survival model estimated the likelihood of series completion among 9-14-year-old adolescents. From 2014 to 2018, 560,806 adolescents received a Tdap vaccine of which 172,604 (30.8%) received the HPV vaccines on the same day. Tdap-HPV vaccination bundling (per 100 Tdap vaccinations) increased nationally, from 22.9 in 2014 to 39.1 in 2018 (P

The human papillomavirus (HPV) vaccine is effective at reducing the incidence of cervical cancer caused by HPV. Studies have shown that 1 dose of the HPV vaccine offers comparable protection against genital HPV infection as additional doses; however, it is unknown whether oral HPV prevalence also differs by number of vaccine doses. We examined differences in prevalence of oral HPV by number of doses using the National Health and Nutrition Examination Survey from 2009 to 2016. The prevalence of HPV 6, 11, 16, and 18 infections was statistically significantly lower in individuals who received 1 dose (0.3%, 95% confidence interval [CI] = 0.0% to 0.9%) or 2-3 doses (0.4%, 95% CI = 0.0% to 1.2%) compared with unvaccinated individuals (1.2%, 95% CI = 0.9% to 1.6%). Smokers, individuals who initiated oral sex at age 17 years or younger, and those with more than 2 oral sexual partners had higher rates of oral HPV infection. Ongoing prospective studies are essential to further evaluate the efficacy of a single-dose regimen for prevention of oral HPV.

Key Points Question Do US counties with differing levels of income and urbanicity vary in rates of suicide among people after cancer diagnosis? Findings In this cohort study that included 5 362 782 people with a cancer diagnosis, there was a significantly higher suicide risk in those living in the lowest-income counties and in rural settings. The risk was highest in the first year after diagnosis and remained higher in those living in the lowest-income counties 10 or more years after diagnosis. Meaning This study’s findings suggest that efforts to provide increased preventive mental health services for individuals with cancer, especially for those living in low-income and rural areas, are needed., Importance Studies suggest the risk of suicide among people with cancer diagnosis is higher compared with the general population. However, little is known about how suicide risk among people diagnosed with cancer might vary according to area-level income and rurality. Objective To examine whether the risks and patterns of suicide mortality among people with a cancer diagnosis differ by US county-level median income and rural or urban status. Design, Setting, and Participants A retrospective, population-based cohort study following up individuals who were diagnosed with cancer between January 1, 2000, and December 31, 2016, was conducted. The Surveillance, Epidemiology, and End Results Program 18 registries (SEER 18) database was used to obtain data on persons diagnosed with a first primary malignant tumor. Comparisons with the general US population were based on mortality data collected by the National Center for Health Statistics. Analyses were conducted from February 22 to October 14, 2020. Exposures County-level median household income and urban or rural status. Main Outcomes and Measures Standardized mortality ratios (SMRs) of suicide deaths and annual percentage changes (APCs) of SMRs. Results The SEER 18 database included 5 362 782 persons with cancer diagnoses living in 635 counties. Most study participants were men (51.2%), White (72.2%), and older than 65 years (49.7%). Among them, 6357 persons died of suicide (SMR, 1.41; 95% CI, 1.38-1.44). People with cancer living in the lowest-income counties had a significantly higher risk (SMR, 1.94; 95% CI, 1.76-2.13) than those in the highest-income counties (SMR, 1.30; 95% CI, 1.26-1.34). Those living in rural counties also had significantly higher SMR than those in urban counties (SMR, 1.81; 95% CI, 1.70-1.92 vs SMR, 1.35; 95% CI, 1.32-1.39). For all county groups, the SMRs were the highest within the first year following cancer diagnosis. However, among people living in the lowest-income counties, the risk remained significantly high even after 10 or more years following cancer diagnosis (SMR, 1.83; 95% CI, 1.31-2.48). The comparative risk of suicide mortality within 1 year following cancer diagnosis significantly decreased over the years but then plateaued in the highest-income (2005-2015: APC, 2.03%; 95% CI, −0.97% to 5.13%), lowest-income (2010-2015: APC, 4.80%; 95% CI, −19.97% to 37.24%), and rural (2004-2015: APC, 1.83; 95% CI, −1.98% to 5.79%) counties. Conclusions and Relevance This cohort study showed disparities in suicide risks and their patterns among people diagnosed with cancer by county-level income and rural or urban status. The findings suggest that additional research and effort to provide psychological services addressing these disparities among people with cancer may be beneficial., This cohort study examines the risk of suicide among US individuals with a cancer diagnosis by income and in rural and urban settings.

This cohort study examines rates of cervical cancer screening in Puerto Rico among women with Medicaid health coverage following the 2017 hurricanes, earthquakes in late 2019-2020, and the 2020 COVID-19 lockdown.

Human papillomavirus (HPV)-associated cancer burden is rising in the United States. Trends in the incidence by county-level income and smoking prevalence remain undescribed. We used the Surveillance, Epidemiology, and End Results 21 database to ascertain HPV-associated cancers during 2000-2018. Trends were estimated by county-level income and smoking prevalence quartiles. Anal and vulvar cancer incidence among women and anal cancer incidence among men increased markedly in the lowest-income counties, whereas the increases were slower in the highest-income counties (eg, for vulvar cancer, incidence increased 1.9% per year, 95% confidence interval [CI] = 0.9% to 2.9%, in the lowest-income counties vs 0.8% per year, 95% CI = 0.6% to 1.1%, in the highest-income counties). In recent years, cervical cancer incidence plateaued (0.0% per year [95% CI = −0.5% to 0.5%]) in the highest-income counties; in the lowest-income counties, the annual percentage change was 1.6% per year (95% CI = −0.7% to 4.0%). Counties with high smoking prevalence had marked increases in incidence compared with their counterparts (eg, anal cancer among men increased 4.4% per year [95% CI = 2.7% to 6.0%] for those living in counties with the highest smoking prevalence vs 1.2% per year [95% CI = 0.7% to 1.7%] for those living in counties with the lowest smoking prevalence). Improved and targeted prevention is needed to combat the widening disparities.

This study uses national cancer incidence data to evaluate calendar trends in cervical cancer incidence by age at diagnosis.

Importance In the US, safety concern has been identified as a primary barrier to initiating the human papillomavirus (HPV) vaccine. It is unclear if the public's sentiment concerning HPV vaccine safety aligns with postmarketing vaccine safety surveillance data. Objective To perform a parallel assessment of trends in HPV vaccine safety concerns and HPV vaccine adverse event (AE) reporting. Design, Setting, and Participants This study was a cross-sectional analysis of the National Immunization Survey (NIS) and Vaccine Adverse Event Reporting System (VAERS). Participants in the NIS were adolescents aged 13 to 17 years. AEs were reported to VAERS by patients, health care clinicians, or other sources. Statistical analysis was performed from October 2020 to May 2021. Main Outcomes and Measures Secular trends in HPV vaccine safety concerns and spontaneous AE reporting for HPV vaccination from 2015 to 2018. Results Caregivers of 39 364 unvaccinated adolescents with a mean (SD) age of 15.57 (0.08) years (26 996 White adolescents [62.9%], 22 707 male adolescents [56.1%], 11 392 privately insured [62.6%], and 32 674 above the poverty level [79.3%]) reported their reasons for not initiating the HPV vaccine series in the 2015-2018 NIS. Citing safety concerns as the primary reason for not initiating the HPV vaccine series increased from 13.0% (95% CI, 12.1%-14.0%) in 2015 to 23.4% (95% CI, 21.8%-25.0%) in 2018 (P for trend

Background: Racial/ethnic minorities generally have a lower knowledge of human papillomavirus (HPV) and the HPV vaccine than non-Hispanic Whites. They are also less likely to have a regular healthcare provider (HCP). Given the role of HCPs in disseminating health information, we evaluated whether racial/ethnic disparities in HPV knowledge are moderated by regular HCP status. Methods: Data from the Health Information National Trends Survey Five (HINTS 5) Cycles One and Two (2017–2018) were analyzed. HPV and HPV vaccine knowledge were compared by regular HCP status across race/ethnicities. Independent partially-adjusted multivariable logistic regression models were used to assess the association between race/ethnicity and knowledge after controlling for sociodemographic characteristics. The resulting adjusted odds ratios were compared to those from fully-adjusted models that included HCP status. Results: After adjusting for regular HCP status, differences in knowledge persisted between racial/ethnic groups. Compared to Whites, Hispanics and Other race/ethnicities had significantly lower odds of having heard of HPV. Blacks, Hispanics, and Other race/ethnicities had significantly lower odds of having heard of the HPV vaccine. Conclusion: Racial/ethnic minorities had significantly lower levels of knowledge despite HCP status. These data suggest the need to address disparities in health information and strengthen provider–patient communication regarding HPV and the HPV vaccine.

Background Obesity is a significant risk factor of several cancers that imposes a substantial economic burden on US healthcare that remains to be quantified. We estimated the excess costs and economic burden of obesity-related cancers in the United States. Methods From the Medical Expenditure Panel Survey (2008-2015) data, we identified 19 405 cancer survivors and 175 498 non-cancer individuals. We estimated annual health expenditures using generalized linear regression with log link and gamma distribution by cancer types (stratified by 11 obesity-related cancers and other cancer types), controlling for sociodemographic and clinical characteristics. All cost estimates were adjusted to 2015 USD value. Results The average annual total health expenditures were $21 503 (95% CI, $20 946-$22 061) for those with obesity-related cancer and $13 120 (95% CI, $12 920-$13 319) for those with other cancer types. There was a positive association between body mass index and health expenditures among cancer survivors: for each additional 5-unit increase in body mass index, the average predicted expenditures increase by $1503 among those with obesity-related cancer and by $722 among those with other cancers. With adjustments for sociodemographic and clinical characteristics, the mean incremental expenditures of treating obesity-related cancer were 2.1 times higher than those of other cancers ($4492 vs $2139) and more considerable among the non-elderly cancer population. Obesity-related cancers accounted for nearly 43.5% of total direct cancer care expenditures, estimated at $35.9 billion in 2015. Conclusion The economic burden of obesity-related cancer in the United States is substantial. Our findings suggest a need for the inclusion of comprehensive obesity prevention and treatment in cancer care.

We report combined experimental and simulation studies which reveal that the structural integrity of insulin hexamer, the storehouse of the important hormone in our body, is compromised by the interactions with ethanol. X-ray crystal structures suggest that ethanol replaces water molecules inside the insulin hexamer cavity. At the maximum physiologically tolerable concentration of ethanol (∼0.6% v/v), molecular dynamics simulations show that ethanol molecules get exchanged between the bulk and the cavity with a free energy cost of ∼5 kcal mol-1. However, biological time scales are orders of magnitude longer than that achievable by molecular dynamics simulations. Hence, to accelerate the process we investigate insulin hexamer in ∼30% v/v ethanol concentration. We find that the entrance and exit of ethanol from the hexamer cavity lead to the modification of atomic contacts in the protein. This causes large-scale fluctuations that force the protein out of its native state free energy minimum. Structural perturbations are also observed at lower ethanol concentration. The computational findings are consistent with dynamic light scattering experiments that suggest an abrupt reduction in the population of insulin hexamers at a critical ethanol concentration. The structural changes triggered by interaction of ethanol with the insulin hexamer are likely to represent a general dynamic event of amphiphilic cosolvent induced changes in macromolecular assemblies with the consequent effects on cellular homeostasis.

Clinical practice guidelines for treating tobacco use and lung cancer screening guidelines recommend smoking cessation counseling to current smokers by health care professionals. Our objective was to determine the contemporary patterns of current smokers’ discussions about smoking with their health care professionals in the USA. We conducted an observational study of 30,132 current smokers (weighted sample 40,126,006) for the years 2011 to 2015 using data from the National Health Interview Survey. Our main outcome was the proportion of current smokers who had discussions about smoking with their health care professionals. We used the Cochran-Armitage trend test to evaluate the temporal trends in current smokers’ discussions about smoking, and used a multivariable logistic model to determine the predictors of discussions about smoking, controlling for smokers’ demographics, health status, and receipts of lung cancer screening. Our study found the proportion of current smokers who had discussions about smoking with their health care professionals increased from 51.3% in 2011 to 55.4% in 2015 (P-trend

Understanding the patterns of antihypertensive drug use and blood pressure (BP) control among stroke survivors in the “real‐world” setting is important to identify gaps in treatment and control, if any. The objective of our study was to assess trends and patterns in antihypertensive drug use and BP control among stroke survivors in the United States. We performed a retrospective cross‐sectional analysis of the 2003‐2014 National Health and Nutrition Examination Survey (NHANES). Stroke and hypertension diagnoses were self‐reported. Information regarding the use of antihypertensive drugs was collected during an in‐person interview. Measurement of BP was performed by trained medical professionals in mobile examination centers. A total 1244 adult stroke survivors (equating to 6 232 215 stroke survivors nationwide) were identified, of which 956 had hypertension. Antihypertensive drug use increased from 2003 (79.5%) to 2014 (92.2%; P for trend

Objective To estimate the prevalence of high-grade anal dysplasia in women with high-grade dysplasia or carcinoma of the cervix, vagina or vulva. Methods In this cross-sectional study, participants underwent anal cytology, anal HPV testing with Cervista HPV16/18 and high-resolution anoscopy (HRA). Patients with HSIL (high-grade squamous cell intraepithelial lesion) or greater on anal cytology or anal biopsy were referred to a colorectal surgery specialist for further evaluation. Results Seventy-five women were enrolled in the study, including 47 with cervical (cervix group), 10 with vaginal (vagina group), 15 with vulvar (vulva group), 1 with cervical and vaginal, and 2 with vulvar and vaginal disease. The median age in the cervix group (40 years (range 26–69)) was substantially younger than in the vagina (60 years (38–69)) and the vulva (59 years (36–75)) groups. Anal HSIL based on composite endpoints of the most severe cytology or histology result was diagnosed in 6 patients (8.0%). Anal cytology revealed HSIL in 2 (2.7%), atypical squamous cells of undetermined significance (ASCUS) in 12 (16.0%), low-grade squamous cell intraepithelial lesion (LSIL) in 2 (2.7%), and was normal in 59 (78.7%) patients. Anal HPV16/18 test was positive in 15 (20.0%), negative in 48 (64.0%) and insufficient in 12 (16.0%) patients. Of the 6 women with high-grade anal dysplasia, three (50%) had a positive anal HPV16/18 test. No case of anal cancer was observed. Conclusion Our results suggest that the prevalence of anal HSIL is elevated among women with HPV-related lower genital tract dysplasia or cancer. To further support the inclusion of this high-risk group into screening guidelines for anal dysplasia, further studies are necessary to determine what screening strategy is suited to this population.

IntroductionSquamous cell carcinoma of the anus is a common cancer among sexual minority men, especially HIV-positive sexual minority men; however, there is no evidenced-based national screening protocol for detection of anal precancers. Our objective is to determine compliance with annual anal canal self-sampling or clinician-sampling for human papillomavirus (HPV) DNA.Methods and analysisThis is a prospective, randomised, two-arm clinical study to evaluate compliance with annual home-based versus clinic-based HPV DNA screening of anal canal exfoliated cells. The setting is primary care community-based clinics. Recruitment is ongoing for 400 HIV-positive and HIV-negative sexual minority men and transgender persons, aged >25 years, English or Spanish speaking, no current use of anticoagulants other than nonsteroidal anti-inflammatory drugs and no prior diagnosis of anal cancer. Participants are randomised to either receive a swab in the mail for home-based collection of an anal canal specimen at 0 and 12 months (arm 1) or attend a clinic for clinician collection of an anal canal specimen at 0 and 12 months (arm 2). Persons will receive clinic-based Digital Anal Rectal Examinations and high-resolution anoscopy-directed biopsy to assess precancerous lesions, stratified by study arm. Anal exfoliated cells collected in the study are assessed for high-risk HPV persistence and host/viral methylation. The primary analysis will use the intention-to-treat principle to compare the proportion of those who comply with 0-month and 12-month sampling in the home-based and clinic-based arms. The a priori hypothesis is that a majority of persons will comply with annual screening with increased compliance among persons in the home-based arm versus clinic-based arm.Ethics and disseminationThe study has been approved by the Medical College of Wisconsin Human Protections Committee. Results will be disseminated to communities where recruitment occurred and through peer-reviewed literature and conferences.Trial registration numberNCT03489707.