Retrospective study of a pilot program focused on educating dental patients on human papillomavirus and vaccination in a hospital setting.

INTRODUCTION: Human papillomavirus (HPV) is an epidemic currently affecting 80 million people in the United States. The HPV virus can be passed from one person to another via sexual intercourse, oral sex, open mouth kissing and skin-to-skin contact. In some cases, the infection is not eliminated by the immune system and can cause cancer of the head and neck, cervix, anus, and genitals. There has been a rise in oropharyngeal cancer (OPC) associated with HPV, which can be missed on conventional dental screening examinations. Dentists should engage in promoting HPV vaccination as a primary measure for OPC prevention. The goal of this HPV pilot program was to educate and offer same day HPV vaccination to dental patients by using a multidisciplinary approach in a hospital setting. METHODS: Patients 18 through 26 years of age who presented to the Erie County Medical Center's dental clinic were approached and educated on HPV. Eligible patients received a direct recommendation for the HPV vaccine. Those interested in same day vaccination were referred to the division of infectious diseases' YOU Center for Wellness. A retrospective chart review was completed for patients who were HPV educated from March 5, 2020, through December 15, 2021. Charts were evaluated for age, sex, race, ethnicity, reason for visit, HPV vaccine referral, and HPV vaccine administration. RESULTS: 326 patients were included in the chart review. The prominent sex, race, and ethnicity were male, Black or African American, and non-Hispanic origin. The median age was 23. Most patients presented to the dental clinic for an emergency visit and were not previously vaccinated against HPV. 110 patients were unvaccinated, and 44 patients were referred to the division of infectious disease for same day vaccination. Of these 44, 24 patients initiated the vaccination process. Five patients received all three doses, three patients received two doses, and 16 patients received one dose. CONCLUSION: This pilot program successfully vaccinated 24 patients with at least a single dose of the HPV vaccine. This multidisciplinary model can be implemented in other health care settings.

Human Papillomavirus Vaccination in Pediatric, Adolescent, and Young Adult Cancer Survivors-Opportunity to Address Gaps in Cancer Prevention and Survivorship.

The risks of secondary cancers associated with human papillomavirus (HPV) infection are as much as three times higher for survivors of pediatric, adolescent, and young adult cancer (PYAC) compared to the general population. Despite this, HPV vaccination rates among PYAC survivors remain low. Whereas pediatric oncology providers endorse HPV vaccination of PYAC survivors, many lack the resources or opportunities to intervene. The responsibility of HPV vaccination, therefore, falls to primary care providers and practices. This article provides an overview of the challenges with HPV vaccination that are distinct to PYAC survivors and discusses potential strategies to increase HPV vaccine coverage in this population.

TRiCit: A High-Throughput Approach to Detect Trichomonas vaginalis from ITS1 Amplicon Sequencing.

Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most common non-viral sexually transmitted infection (STI) worldwide, affecting over 174 million people annually and is frequently associated with reproductive co-morbidities. However, its detection can be time-consuming, subjective, and expensive for large cohort studies. This case-control study, conducted at the Mount Sinai Adolescent Health Center in New York City, involved 36 women with prevalent TV infections and 36 controls. The objective was to examine Internal Transcribed Spacer region-1 (ITS1) amplicon-derived communities for the detection of prevalent TV infections with the same precision as clinical microscopy and the independent amplification of the TV-specific TVK3/7 gene. DNA was isolated from clinician-collected cervicovaginal samples and amplified using ITS1 primers in a research laboratory. Results were compared to microscopic wet-mount TV detection of concurrently collected cervicovaginal samples and confirmed against TV-specific TVK3/7 gene PCR. The area under the receiver operating characteristics curve (AUC) for diagnosing TV using ITS1 communities was 0.92. ITS1 amplicons displayed an intra-class correlation coefficient (ICC) of 0.96 (95% CI: 0.93-0.98) compared to TVK3/7 PCR fragment testing. TV cases showed an increased risk of bacterial vaginosis (BV) compared to the TV-negative controls (OR = 8.67, 95% CI: 2.24-48.54, p-value = 0.0011), with no significant differences regarding genital yeast or chlamydia infections. This study presents a bioinformatics approach to ITS1 amplicon next-generation sequencing that is capable of detecting prevalent TV infections. This approach enables high-throughput testing for TV in stored DNA from large-scale epidemiological studies.

Long-acting reversible contraception and condom use: A cohort study of female adolescents and young adults in New York City.

OBJECTIVES: This study aimed to determine whether condom use varied between adolescents and young women using long-acting reversible contraception (LARC) vs non-LARC hormonal methods and assess if the initiation of LARC was associated with lower condom use. STUDY DESIGN: This study used data from a large longitudinal study of sexually active females aged 13-25 years. Questionnaires assessed contraception, condom use, sexual history, and partner characteristics at the baseline visit and every 6 months. Log-binomial regression analyses examined associations between hormonal contraceptive methods and condom use, and the moderating effects of age and number of sexual partners. Exploratory analyses compared condom use based on partner characteristics. RESULTS: Of 1512 participants, 1116 reported LARC or non-LARC hormonal method use during any study visit. Among baseline and new LARC users, 75.7% and 84.7% reported intrauterine device (IUD) use, respectively. Condom use at baseline among hormonal non-LARC users (37.5%) was significantly higher (p < 0.01) than LARC users (23.5%). Condom use among LARC vs non-LARC users was moderated by age in that LARC was associated with lower condom use among participants aged 13-18 years, but not those aged 19-25 years. Number of sexual partners was not a significant moderator. Among participants with increased sexually transmitted infection (STI) risk based on partner characteristics, LARC users had lower condom use compared to non-LARC users. CONCLUSIONS: Condom discontinuation was common following initiation of LARC and hormonal non-LARC methods. However, condom use was lower in LARC users at baseline, among younger adolescents, and if partners had risk factors for STIs. IMPLICATIONS: Condom discontinuation following initiation of highly effective contraception increases the risk of STI. Young women using LARC may be at greater risk than non-LARC users given lower condom use despite having partners with risk factors for STIs. Condom use counseling for STI protection is critical for adolescents.

Examining the Barriers and Opportunities for Human Papillomavirus Vaccine Delivery in Cancer Care Settings: A Mixed-Methods Study.

Although pediatric, adolescent, and young adult (PAYA) cancer survivors are at increased risks for secondary cancers, their HPV vaccine uptake rates are poor. Therefore, we conducted a mixed-methods study to identify the barriers and opportunities for HPV vaccine delivery among PAYA cancer care providers. We distributed a semistructured questionnaire to a professional organization comprised of PAYA oncology and hematology healthcare providers between April and July 2022. Questionnaire measures included demographic and practice characteristics, HPV vaccine knowledge, willingness, barriers, opportunities, and roles for HPV vaccine delivery. Descriptive characteristics were generated for quantitative data, and content analysis was used to identify themes. A total of 49 providers responded to our survey. A majority were female (68%) and non-Hispanic white (74%). Approximately 76% were oncology or hematology physicians, and most worked in a cancer center or children's hospital (86%). Over half (63%) had been practicing for >15 years, and a majority saw patients ages 11 to 17. Although less than half reported discussing HPV vaccination with their patients, 69% were willing to become involved in HPV vaccine delivery. The most frequently reported barriers identified in our content analysis were related to system-level factors. Furthermore, providers identified opportunities within cancer prevention education, transitions in care, and at the system-level. Although barriers to HPV vaccination persist in cancer care, most providers perceived there to be opportunities to become involved in HPV vaccine delivery. Identifying strategies for PAYA oncology and hematology healthcare providers to adopt a stronger role in HPV vaccination remains a significant opportunity for future implementation research. PREVENTION RELEVANCE: This mixed-methods study is the first to investigate and assess barriers and opportunities for HPV vaccine delivery among PAYA cancer healthcare providers. Our findings can serve as an important framework for future implementation research targeted towards HPV vaccine delivery in cancer clinical settings. See related Spotlight, p. 545.

Establishment of a diverse head and neck squamous cancer cell bank using conditional reprogramming culture methods.

Most laboratory models of head and neck squamous cell cancer (HNSCC) rely on established immortalized cell lines, which carry inherent bias due to selection and clonality. We established a robust panel of HNSCC tumor cultures using a "conditional reprogramming" (CR) method, which utilizes a rho kinase inhibitor (Y-27632) and co-culture with irradiated fibroblast (J2 strain) feeder cells to support indefinite tumor cell survival. Sixteen CR cultures were successfully generated from 19 consecutively enrolled ethnically and racially diverse patients with HNSCC at a tertiary care center in the Bronx, NY. Of the 16 CR cultures, 9/16 were derived from the oral cavity, 4/16 were derived from the oropharynx, and 3/16 were from laryngeal carcinomas. Short tandem repeat (STR) profiling was used to validate culture against patient tumor tissue DNA. All CR cultures expressed ΔNp63 and cytokeratin 5/6, which are markers of squamous identity. Human papillomavirus (HPV) testing was assessed utilizing clinical p16 staining on primary tumors, reverse transcription polymerase chain reaction (RT-PCR) of HPV16/18-specific viral oncogenes E6 and E7 in RNA extracted from tumor samples, and HPV DNA sequencing. Three of four oropharyngeal tumors were p16 and HPV-positive and maintained HPV in culture. CR cultures were able to establish three-dimensional spheroid and murine flank and orthotopic tongue models. CR methods can be readily applied to all HNSCC tumors regardless of patient characteristics, disease site, and molecular background, providing a translational research model that properly includes patient and tumor diversity.

Human papillomavirus vaccination uptake among childhood cancer survivors in Western New York.

INTRODUCTION: The risk of human papillomavirus (HPV)-associated cancers is significantly higher among survivors of a childhood cancer compared to the general population. Despite this, their HPV vaccine uptake rates are lower. We examined factors related to HPV vaccine uptake among childhood cancer survivors from Western New York over 13 years following the introduction of HPV vaccines. METHODS: Retrospective review of patients diagnosed with invasive or noninvasive cancerous conditions at age 9 or younger treated at Roswell Park Oishei Children's Cancer and Blood Disorder Program. We matched vaccine date information for patients aged 9-26 years between 2006 and 2020 from the New York State Immunization Information System. Demographic and cancer-related information was abstracted from electronic medical records. Cumulative vaccine uptake was assessed by Kaplan-Meier and Cox proportional hazards regression models. RESULTS: A total of 284 patients were included in the analyses. Most were non-Hispanic/White (80.3%) and resided in a metropolitan area (81.7%). Approximately half had leukemia or lymphoma (54.9%), and most received chemotherapy. Females were more likely to initiate the HPV vaccine and did so sooner (median = 5.5 years) than males (median = 5.7 years; log-rank p = .301). Patients who were older at vaccine eligibility and males who received blood product transfusions were significantly less likely to initiate the HPV vaccine. CONCLUSION: While rates of HPV vaccine initiation have been increasing with time among childhood cancer survivors, they remain low overall, with differences seen by treatment and diagnosis. Our findings support the need for further research to optimize HPV vaccine delivery in cancer care.

Do cutaneous human papillomavirus genotypes affect head and neck cancer? Evidence and bias-correction from a case-control study.

BACKGROUND: Three genera of human papillomavirus (HPV) infect the oral cavity and oropharynx- alpha (α), beta (ß) and gamma (γ). While α-HPV infection is an established risk factor for head and neck cancers (HNC), the role of other genera remains unclear. We aimed to estimate the effect of α-, ß-, γ-HPV on HNC using a hospital-based case-control study. METHODS: We recruited incident HNC cases (396) and controls (439), frequency-matched by age and sex from four main referral hospitals in Montreal, Canada. We collected information on sociodemographic and behavior characteristics using in-person interviews, and tested rinse, brush and tumor specimens for HPV genotypes. We estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the effect of HPV on HNC using logistic regression, adjusting for confounding. We conducted probabilistic bias analysis to account for potential exposure misclassification, selection bias, and residual confounding. RESULTS: α-HPV genus had a strong effect on HNC, particularly HPV16 (aOR=22.6; 95% CI: 10.8, 47.2). ß-HPV was more common among controls (aOR=0.80; 95% 0.57, 1.11). After adjustment for HPV16, we found weaker evidence for γ-HPV (aOR= 1.29; 95% CI: 0.80, 2.08). Combined bias analyses for HPV16 increased the strength of the point estimate, but added imprecision (aOR=54.2, 95% CI: 10.7, 385.9). CONCLUSIONS: α-HPV, especially HPV16, appears to increase the risk for HNC, while there is little evidence for an effect of ß- or γ-HPV. ß-HPV may have a preventive effect, while γ-HPV may increase the risk of HNC, although to a lesser extent than that of α-HPV. Results for cutaneous HPV were imprecise and less conclusive. Due to possible epidemiologic biases, the true relation between HPV and HNC could be underestimated in the literature. Further improvement in current methods and more studies of the biologic mechanisms of the three genera in HNC development are warranted.

Absolute Risk of Oropharyngeal Cancer After an HPV16-E6 Serology Test and Potential Implications for Screening: Results From the Human Papillomavirus Cancer Cohort Consortium.

PURPOSE: Seropositivity for the HPV16-E6 oncoprotein is a promising marker for early detection of oropharyngeal cancer (OPC), but the absolute risk of OPC after a positive or negative test is unknown. METHODS: We constructed an OPC risk prediction model that integrates (1) relative odds of OPC for HPV16-E6 serostatus and cigarette smoking from the human papillomavirus (HPV) Cancer Cohort Consortium (HPVC3), (2) US population risk factor data from the National Health Interview Survey, and (3) US sex-specific population rates of OPC and mortality. RESULTS: The nine HPVC3 cohorts included 365 participants with OPC with up to 10 years between blood draw and diagnosis and 5,794 controls. The estimated 10-year OPC risk for HPV16-E6 seropositive males at age 50 years was 17.4% (95% CI, 12.4 to 28.6) and at age 60 years was 27.1% (95% CI, 19.2 to 45.4). Corresponding 5-year risk estimates were 7.3% and 14.4%, respectively. For HPV16-E6 seropositive females, 10-year risk estimates were 3.6% (95% CI, 2.5 to 5.9) at age 50 years and 5.5% (95% CI, 3.8 to 9.2) at age 60 years and 5-year risk estimates were 1.5% and 2.7%, respectively. Over 30 years, after a seropositive result at age 50 years, an estimated 49.9% of males and 13.3% of females would develop OPC. By contrast, 10-year risks among HPV16-E6 seronegative people were very low, ranging from 0.01% to 0.25% depending on age, sex, and smoking status. CONCLUSION: We estimate that a substantial proportion of HPV16-E6 seropositive individuals will develop OPC, with 10-year risks of 17%-27% for males and 4%-6% for females age 50-60 years in the United States. This high level of risk may warrant periodic, minimally invasive surveillance after a positive HPV16-E6 serology test, particularly for males in high-incidence regions. However, an appropriate clinical protocol for surveillance remains to be established.

Oral human papillomavirus prevalence, persistence, and risk-factors in HIV-positive and HIV-negative adults.

BACKGROUND: HIV has been shown to increase the likelihood of oral HPV infection. In this study, we evaluated the risk of oral HPV in HIV infected patients compared with HIV-negative controls. METHODS: 101 healthy adult volunteers (HIV-) and 245 adults living with HIV infection (HIV+) were recruited from 5 academic medical centers. Questionnaires and saliva samples were obtained every 3-8 months over a period of 2 years (2015-2017). DNA was isolated from the saliva samples and tested for 18 high- and low-risk genotypes. RESULTS: Oral HPV was detected in 23% of HIV + vs. 10% of HIV- participants (p < 0.0001). Men had a higher oral HPV prevalence than women (27% vs. 15% HIV+, p = 0.03, 16% vs. 5% HIV-, p = 0.01). Risk factors among HIV + participants included more lifetime deep kissing and oral sex partners, and history of AIDS. Persistent oral HPV was detected in 23% of HIV + vs. 5% of HIV- participants (p < 0.001). Among 8 HIV + participants with CD4 counts <200 cell/µL none had cleared their HPV infection during the study. CONCLUSIONS: Risk of oral HPV infection and persistence was significantly higher in HIV + adults with a history of poorly controlled HIV, which may put them at increased risk of HPV-associated cancer.

molBV reveals immune landscape of bacterial vaginosis and predicts human papillomavirus infection natural history.

Bacterial vaginosis (BV) is a highly prevalent condition that is associated with adverse health outcomes. It has been proposed that BV's role as a pathogenic condition is mediated via bacteria-induced inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. Here, we develop molBV, a 16 S rRNA gene amplicon-based classification pipeline that generates a molecular score and diagnoses BV with the same accuracy as the current gold standard method (i.e., Nugent score). Using 3 confirmatory cohorts we show that molBV is independent of the 16 S rRNA region and generalizable across populations. We use the score in a cohort without clinical BV states, but with measures of HPV infection history and immune markers, to reveal that BV-associated increases in the IL-1ß/IP-10 cytokine ratio directly predicts clearance of incident high-risk HPV infection (HR = 1.86, 95% CI: 1.19-2.9). Furthermore, we identify an alternate inflammatory BV signature characterized by elevated TNF-α/MIP-1ß ratio that is prospectively associated with progression of incident infections to CIN2 + (OR = 2.81, 95% CI: 1.62-5.42). Thus, BV is a heterogeneous condition that activates different arms of the immune response, which in turn are independent risk factors for HR-HPV clearance and progression. Clinical Trial registration number: The CVT trial has been registered under: NCT00128661.

Impact of COVID-19 Mitigation Measures on Inner-City Female Youth in New York City.

PURPOSE: New York City (NYC) was the global epicenter of the COVID-19 pandemic in spring 2020. A "shelter in place" mandate was issued in March 2020. The effect on vulnerable populations of adolescent and young adult females has not been well documented. METHODS: We administered a monthly online survey between May and November 2020 to adolescent and young adult females participating in a longitudinal study at Mount Sinai Adolescent Health Center. Surveys asked about death of loved ones, financial impacts, social interactions, exposure to dangerous situations, and mental health impacts. Differences in responses by age, race/ethnicity, and living situation were assessed, and compared to data obtained on the same cohort prior to the pandemic. RESULTS: Four hundred seventeen females aged 15-28 years completed at least one survey, 94% of whom were youth of color. A third of responders (33%) had lost relatives or other people they were close to (loved ones). Most (68%) reported one or more financial losses, and 21% reported food insecurity, with those not living with parents or a guardian experiencing significantly higher rates. One in 10 reported experiencing sexual abuse or interpersonal partner violence during the "shelter in place" period. Over a third (37%) reported symptoms of clinical depression, which represented a significant increase compared to before the pandemic (p = .01). The negative financial impacts and higher proportion of patients with depressive symptomatology remained elevated for adolescents without support at home. CONCLUSIONS: The COVID-19 pandemic had unprecedented negative short-term financial and psychosocial health impacts on inner-city female youth with potential long-term negative impacts.

Impact of Nonadherence to NCCN Adjuvant Radiotherapy Initiation Guidelines in Head and Neck Squamous Cell Carcinoma in an Underserved Urban Population.

BACKGROUND: Nonadherence to NCCN Guidelines during time from surgery to postoperative radiotherapy (S-PORT) can alter survival outcomes in head and neck squamous cell carcinomna (HNSCC). There is a need to validate this impact in an underserved urban population and to understand risk factors and reasons for delay. We sought to investigate the impact of delayed PORT with outcomes of overall survival (OS) in HNSCC, to analyze predictive factors of delayed PORT, and to identify reasons for delay. METHODS: We conducted a retrospective cohort study in an urban, community-based academic center. A total of 184 patients with primary HNSCC were identified through the Montefiore Medical Center cancer registry who had been treated between March 1, 2005, and March 8, 2017, and met the inclusion and exclusion criteria. The primary exposure was S-PORT. OS, recurrence, and risk factors and reasons for treatment delay were the main outcomes and measures. RESULTS: Among 184 patients with HNSCC treated with PORT, the median S-PORT was 48.5 days (interquartile range, 41-67 days). The S-PORT threshold that optimally differentiated worse OS outcomes was >50 days (46.7% of our cohort; n=86). Independent of other relevant factors, patients with HNSCC and S-PORT >50 days had worse OS (hazard ratio, 2.30; 95% CI, 1.34-3.95) and greater recurrence (odds ratio, 3.51; 95% CI, 1.31-9.39). Predictors of delayed S-PORT included being underweight or obese, prolonged postoperative length of stay, and age >70 years. The most frequent reasons for PORT delay were complications related to surgery (22.09%), unrelated medical comorbidities (18.60%), and nonadherence/missed appointments (6.98%). CONCLUSIONS: Delayed PORT beyond 50 days after surgery was associated with decreased OS and greater recurrence. Identification of predictive factors and reasons for treatment delay helps to target at-risk patients and facilitates interventions in underserved populations.

Anti-HPV16 Antibody Titers Prior to an Incident Cervical HPV16/31 Infection.

The goal of this study was to investigate the serological titers of circulating antibodies against human papillomavirus (HPV) type 16 (anti-HPV16) prior to the detection of an incident HPV16 or HPV31 infection amongst vaccinated participants. Patients were selected from a prospective post-HPV vaccine longitudinal cohort at Mount Sinai Adolescent Health Center in Manhattan, NY. We performed a nested case-control study of 43 cases with incident detection of cervical HPV16 (n = 26) or HPV31 (n = 17) DNA who had completed the full set of immunizations of the quadrivalent HPV vaccine (4vHPV). Two control individuals whom had received three doses of the vaccine (HPV16/31-negative) were selected per case, matched on age at the first dose of vaccination and follow-up time in the study: a random control, and a high-risk control that was in the upper quartile of a sexual risk behavior score. We conducted an enzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin G (IgG) antibodies specific to anti-HPV16 virus-like particles (VLPs). The results suggest that the average log antibody titers were higher among high-risk controls than the HPV16/31 incident cases and the randomly selected controls. We show a prospective association between anti-HPV16 VLP titers and the acquisition of an HPV16/31 incident infection post-receiving three doses of 4vHPV vaccine.

Incidence and Types of Human Papillomavirus Infections in Adolescent Girls and Young Women Immunized With the Human Papillomavirus Vaccine.

Importance: Rates of human papillomavirus (HPV) infection have decreased since the introduction of HPV vaccines in populations with high vaccine uptake. Data are limited for adolescent and young adult populations in US metropolitan centers. Objective: To determine HPV infection rates in adolescent girls and young women aged 13 to 21 years in New York City following HPV vaccination. Design, Setting, and Participants: This cohort study of type-specific cervical HPV detection was conducted at a large adolescent-specific integrated health center in New York City between October 2007 and September 2019. Participants included an open cohort of adolescent girls and young adult women who received the HPV vaccine (Gardasil; Merck & Co) over a 12-year period following HPV vaccination introduction. Data analysis was concluded September 2019. Exposures: Calendar date and time since receipt of first vaccine dose. Main Outcomes and Measures: Temporal associations in age-adjusted postvaccine HPV rates. Results: A total of 1453 participants, with a mean (SD) age at baseline of 18.2 (1.4) years, were included in the cohort (African American with no Hispanic ethnicity, 515 [35.4%] participants; African American with Hispanic ethnicity, 218 [15.0%] participants; Hispanic with no reported race, 637 [43.8%] participants). Approximately half (694 [47.8%] participants) were vaccinated prior to coitarche. Age-adjusted detection rates for quadrivalent vaccine types (HPV-6, HPV-11, HPV-16, and HPV-18) and related types (HPV-31, and HPV-45) decreased year over year, with the largest effect sizes observed among individuals who had been vaccinated before coitarche (adjusted odds ratio [aOR], 0.81; 95% CI, 0.67-0.98). By contrast, detection was higher year over year for nonvaccine high-risk cervical HPV types (aOR, 1.08; 95% CI, 1.04-1.13) and anal HPV types (aOR, 1.11; 95% CI, 1.05-1.17). The largest effect sizes were observed with nonvaccine types HPV-56 and HPV-68. Conclusions and Relevance: Whereas lower detection rates of vaccine-related HPV types were observed since introduction of vaccines in female youth in New York City, rates of some nonvaccine high-risk HPV types were higher. Continued monitoring of high-risk HPV prevalence is warranted.

Genes Relevant to Tissue Response to Cancer Therapy Display Diurnal Variation in mRNA Expression in Human Oral Mucosa.

BACKGROUND: To address a critical gap for application of cancer chronotherapy of when would be the best time(s) for treating an individual cancer patient, we conducted a pilot study to characterize diurnal variations of gene expression in oral mucosal tissue, which is vulnerable to damage from cancer therapies. METHODS: We conducted RNA-seq assay on individual oral mucosal samples collected from 11 healthy volunteers every 4 hours (6 time points). Using a cosine-based method, we estimated the individual and average values of peak-time and amplitude for each gene. Correlations between gene expression peak-times and age was examined, adjusting for individual's sleep timing. RESULTS: Among candidate gene pathways that are relevant to treatment response, 7 of 16 genes (PER3, CIART, TEF, PER1, PER2, CRY2, ARNTL) involved in circadian regulation and 1 of 118 genes (WEE1) involved in cell cycle regulation achieved p-value ≤ 0.1 and relative amplitude>0.1. The average peak times were approximately 10:15 for PER3, CIART and TEF, 10:45 for PER1, 13:00 for WEE1, PER2 and CRY2, and 19:30 for ARNTL. Ranges in peak times across individuals differed by gene (e.g., 8 hours for PER1; 16.7 hours for WEE1). Older people had later peak times for PER1 (r = 0.77, p = 0.03) and PER3 (r = 0.69, p-value = 0.06). CONCLUSION: In oral mucosa, expression of some genes relevant to treatment response displayed diurnal variation. These genes may be candidates for development of biomarkers for optimizing individual timing of cancer therapy using non-invasively collected oral mucosa.

Neighborhood Profiles and Body Mass Index Trajectory in Female Adolescents and Young Adults.

PURPOSE: The purpose of this study is to identify distinct neighborhood profiles patterned by key structural, physical, and social characteristics and test whether living in different profiles are associated with body mass index trajectories during adolescence in racial/ethnic minority female youth. METHODS: Participants were 1,328 sexually active female adolescents and young adults aged 14-23 years, predominately Hispanic and black, enrolled in an human papillomavirus type 4 vaccine (Gardasil) surveillance study at a large adolescent health clinic in New York City between 2007 and 2018. Body mass index was calculated from weight and height every 6 months. A comprehensive set of neighborhood structural, social, and physical characteristics from multiple national and state datasets was linked to each participant based on home address. RESULTS: Latent profile analysis revealed five distinct neighborhood profiles in New York City: High Structural/High Social Advantage, Moderate Advantage/Low Crime, Low SES (Socioeconomic Status)/High Activity, Low SES/High Social Advantage, and High Disadvantage. Results from multilevel growth curve analysis revealed that living in Low SES/High Activity neighborhoods was associated with a lower BMI at age 22 (b = -1.32, 95% confidence interval -2.49, -.16), as well as a slower increase in BMI from age 14 to 22 years (b = -.22, 95% confidence interval -.46, .02), compared to the High Disadvantage profile. CONCLUSIONS: Our findings suggest that improving neighborhood structural, social, and physical environments may help promote healthy weight and reduce health disparities during adolescence and young adulthood.

Changes in cannabis, tobacco, and alcohol use among sexually active female adolescents and young adults over a twelve-year period ending in 2019.

BACKGROUND: The United States has experienced an increasing divergence in cannabis, tobacco, and alcohol use among adolescents and young adults (AYA). We assessed the changes in cannabis, tobacco and alcohol use in an inner-city population of predominantly minority AYA females attending a large adolescent-specific health center in New York City. METHODS: This was a longitudinal study of AYA women recruited and followed over a twelve-year period between 2007 and 2019. Lifetime and past 30-day use were assessed by self-administered questionnaire every six months. In addition, we assessed associations with race, ethnicity, sexual behaviors, receipt of social services, living situation at home (e.g., with or without parents), and use of other drugs. RESULTS: Participants included 1549 AYA females aged 13-21 at baseline, 95% of whom were youth of color. Use of cannabis increased significantly over the twelve-year period, with frequent cannabis use (≥20 times in 30-days) increasing almost 18% per year (OR = 1.18; 95%CI:1.13-1.23). In contrast, past 30-day tobacco use declined over the same period (OR = 0.86; 95%CI:0.83-0.89). Past 30-day cannabis use was more likely among African Americans (OR = 1.33; 95%CI:1.08-1.63), women who had sex with both men and women compared to with men only (OR = 1.44; 95%CI:1.18-1.75), recent users of tobacco (OR = 2.20; 95%CI:1.92-2.52) and alcohol (OR = 2.84; 95%CI:2.52-3.20), and ever users of other drugs (OR = 1.69; 95%CI:1.44-1.99), independent of age, time and living situation. CONCLUSIONS: Increasing rates of cannabis use and the association with concurrent tobacco and alcohol use in AYA females underscore the need to screen for unhealthy cannabis use, in addition to tobacco and alcohol, especially among inner-city AYA.

Profiles of Childhood Maltreatment: Associations with Sexual Risk Behavior during Adolescence in a Sample of Racial/Ethnic Minority Girls.

This study examines associations between childhood maltreatment and developmental trajectories of sexual risk behaviors (SRBs) in a sample of 882 sexually active adolescent girls, predominantly Hispanic or Black, assessed every 6 months between 13 and 23 years. Latent profile analyses revealed four distinct maltreatment profiles: Low Maltreatment (76%), Moderate Emotional Neglect Only (15%), Severe Physical/Emotional Abuse (3%), and Severe Sexual Abuse (6%). Multilevel growth analyses showed the Moderate Emotional Neglect Only and Severe Sexual Abuse profiles exhibited more SRBs starting in late adolescence, and the Severe Sexual Abuse profile also exhibited a faster increase than the Low Maltreatment profile. Understanding heterogeneity within maltreated populations may have important implications for healthy sexual development.

Palbociclib Renders Human Papilloma Virus-Negative Head and Neck Squamous Cell Carcinoma Vulnerable to the Senolytic Agent Navitoclax.

We demonstrate that inhibition of cyclin-dependent kinases 4/6 (CDK4/6) leads to senescence in human papillomavirus (HPV)-negative (-) head and neck squamous cell carcinoma (HNSCC), but not in HPV-positive (+) HNSCC. The BCL-2 family inhibitor, navitoclax, has been shown to eliminate senescent cells effectively. We evaluated the efficacy of combining palbociclib and navitoclax in HPV- HNSCC. Three HPV- HNSCC cell lines (CAL27, HN31, and PCI15B) and three HPV+ HNSCC cell lines (UPCI-SCC-090, UPCI-SCC-154, and UM-SCC-47) were treated with palbociclib. Treatment drove reduced expression of phosphorylated Rb (p-Rb) and phenotypic evidence of senescence in all HPV- cell lines, whereas HPV+ cell lines did not display a consistent response by Rb or p-Rb and did not exhibit morphologic changes of senescence in response to palbociclib. In addition, treatment of HPV- cells with palbociclib increased both ß-galactosidase protein expression and BCL-xL protein expression compared with untreated controls in HPV- cells. Co-expression of ß-galactosidase and BCL-xL occurred consistently, indicating elevated BCL-xL expression in senescent cells. Combining palbociclib with navitoclax led to decreased HPV- HNSCC cell survival and led to increased apoptosis levels in HPV- cell lines compared with each agent given alone. IMPLICATIONS: This work exploits a key genomic hallmark of HPV- HNSCC (CDKN2A disruption) using palbociclib to induce BCL-xL-dependent senescence, which subsequently causes the cancer cells to be vulnerable to the senolytic agent, navitoclax.