Time-varying associations of patient and tumor characteristics with cancer survival: an analysis of SEER data across 14 cancer sites, 2004-2017.

PURPOSE: Surveillance, Epidemiology, and End Results (SEER) cancer registries provides information about survival duration and cause of death for cancer patients. Baseline demographic and tumor characteristics such as age, sex, race, year of diagnosis, and tumor stage can inform the expected survival time of patients, but their associations with survival may not be constant over the post-diagnosis period. METHODS: Using SEER data, we examined if there were time-varying associations of patient and tumor characteristics on survival, and we assessed how these relationships differed across 14 cancer sites. Standard Cox proportional hazards models were extended to allow for time-varying associations and incorporated into a competing-risks framework, separately modeling cancer-specific and other-cause deaths. For each cancer site and for each of the five factors, we estimated the relative hazard ratio and absolute hazard over time in the presence of competing risks. RESULTS: Our comprehensive consideration of patient and tumor characteristics when estimating time-varying hazards showed that the associations of age, tumor stage at diagnosis, and race/ethnicity with risk of death (cancer-specific and other-cause) change over time for many cancers; characteristics of sex and year of diagnosis exhibit some time-varying patterns as well. Stage at diagnosis had the largest associations with survival. CONCLUSION: These findings suggest that proportional hazards assumptions are often violated when examining patient characteristics on cancer survival post-diagnosis. We discuss several interesting results where the relative hazards are time-varying and suggest possible interpretations. Based on the time-varying associations of several important covariates on survival after cancer diagnosis using a pan-cancer approach, the likelihood of the proportional hazards assumption being met or corresponding interpretation should be considered in survival analyses, as flawed inference may have implications for cancer care and policy.

Cervicovaginal and Anal Self-Sampling for Human Papillomavirus Testing in a Transgender and Gender Diverse Population Assigned Female at Birth: Comfort, Difficulty, and Willingness to Use.

Purpose: Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face numerous barriers to preventive care, including for cervical cancer screening. At-home human papillomavirus (HPV) testing may expand access to cervical cancer screening for TGD people AFAB. This study assessed the perceptions of TGD individuals AFAB who self-collected cervicovaginal and anal samples. Methods: We recruited TGD individuals AFAB to collect cervicovaginal and anal specimens at home using self-sampling for HPV testing, and individuals reported their perceptions of self-sampling. Associations between demographic and health characteristics and each of comfort of use, ease of use, and willingness to use self-sampling were estimated using robust Poisson regression. Results: Of 137 consenting participants, 101 completed the sample collection and the surveys. The majority of participants reported that the cervicovaginal self-swab was not uncomfortable (68.3%) and not difficult to use (86.1%), and nearly all (96.0%) were willing to use the swab in the future. Fewer participants found the anal swab to not be uncomfortable (47.5%), but most participants still found the anal swab to not be difficult to use (70.2%) and were willing to use the swab in the future (89.1%). Participants were more willing to use either swab if they had not seen a medical professional in the past year. Conclusions: TGD individuals AFAB were willing to use and preferred self-sampling methods for cervicovaginal and anal HPV testing. Developing clinically approved self-sampling options for HPV testing could expand access to cancer screening for TGD populations.

Prevalence and Determinants of Cervicovaginal, Oral, and Anal Human Papillomavirus Infection in a Population of Transgender and Gender Diverse People Assigned Female at Birth.

Purpose: The human papillomavirus (HPV) causes cervicovaginal, oral, and anogenital cancer, and cervical cancer screening options include HPV testing of a clinician-collected sample. Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face many barriers to preventive care, including cancer screening. Self-sampling options may increase access and participation in HPV testing and cancer screening. This study estimated the prevalence of HPV in self-collected cervicovaginal, oral, and anal samples from Midwestern TGD individuals AFAB. Methods: We recruited TGD individuals AFAB for an observational study, mailing them materials to self-collect cervicovaginal, oral, and anal samples at home. We tested samples for high-risk (HR; 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and other HPV genotypes (6, 11, 66, 68, 73, 90) using a polymerase chain reaction mass array test. Prevalence ratios for HPV infection at each site as a function of participant characteristics were estimated in log-binomial models. Results: Out of 137 consenting participants, 102 completed sample collection. Among those with valid tests, 8.8% (HR = 6.6%; HPV 16/18 = 3.3%) were positive for oral HPV, 30.5% (HR = 26.8%; HPV 16/18 = 9.7%) for cervicovaginal HPV, and 39.6% (HR = 33.3%; HPV 16/18 = 8.3%) for anal HPV. A larger fraction of oral (71.4%) than anal infections (50.0%) were concordant with a cervicovaginal infection of the same type. Conclusions: We detected HR cervicovaginal, oral, and anal HPV in TGD people AFAB. It is essential that we reduce barriers to cancer screening for TGD populations, such as through the development of a clinically approved self-screening HPV test.

Changing patterns of cigarette and ENDS transitions in the USA: a multistate transition analysis of adults in the PATH Study in 2017-2019 vs 2019-2021.

Introduction: The use of cigarettes and electronic nicotine delivery system (ENDS) has likely changed since 2019 with the rise of pods and disposables, the outbreak of lung injuries related to vaping THC, flavor bans, and the COVID pandemic. We analyzed patterns of initiation, cessation, and transitions between cigarettes, ENDS, and dual use before and after 2019. Methods: Using the Population Assessment of Tobacco and Health (PATH) Study, we applied a multistate transition model to 28,061 adults in Waves 4-5 (2017-19) and 24,751 adults in Waves 5-6 (2019-21), estimating transition rates for initiation, cessation, and switching products for each period overall and by age group. Results: Cigarette initiation among adults who never used either product decreased from 2017-19 to 2019-21, but ENDS initiation did not significantly change. Persistence of ENDS-only use remained high, with 75-80% still using ENDS only after 1 year. Cigarette-only use transitions remained similar, with about 88% remaining, 7% transitioning to non-current use, and 5% transitioning to dual or ENDS-only use. In contrast, dual use to ENDS-only transitions increased from 9.5% (95%CI: 7.3-11.7%) to 20.1% (95%CI: 17.5-22.7%) per year from 2017-19 to 2019-21, decreasing the persistence of dual use. The dual use to cigarette-only transition remained at about 25%. These changes were qualitatively similar across adult age groups, though adults ages 18-24 years exhibited the highest probability of switching from cigarette-only use to dual use and from dual use to ENDS-only use. Conclusions: Persistence of ENDS use among adults remained high in 2019-21, but a larger fraction of dual users transitioned to ENDS-only use compared to 2017-19. Because the fraction of cigarette-only users switching to dual use remained low, the public health implications of the increased dual use to ENDS-only transition are minimal.

Prevalence and determinants of cervicovaginal, oral, and anal HPV infection in a population of transgender and gender diverse people assigned female at birth.

Introduction: HPV causes oral, cervicovaginal, and anogenital cancer, and cervical cancer screening options include HPV testing of a physician-collected sample. Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face discrimination and stigma in many healthcare settings; are believed to be a lower risk for cervical cancer by many physicians; are less likely to be up to date on preventive health care services such as pelvic health exams; and are more likely to have inadequate results from screening tests. Self-sampling options may increase access and participation in HPV testing and cancer screening. Methods: We recruited 137 TGD individuals AFAB for an observational study, mailing them a kit to self-collect cervicovaginal, oral, and anal samples at home. We tested samples for HPV genotypes 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73 and 90 using a PCR mass array test. Results: 102 participants completed the study. Among those with valid tests, 8.8% were positive for oral HPV, 30.5% were positive for cervicovaginal HPV, and 39.6% were positive for anal HPV. A large fraction of anal (50.0%) and oral (71.4%) infections were concordant with a cervicovaginal infection of the same type. Conclusions: HPV infection in TGD people AFAB may be just as high, if not higher, than in cisgender women. It is essential that we reduce barriers to cancer screening for TGD populations, such as through the development of a clinically approved self-screening HPV test.

Cervicovaginal and anal self-sampling for HPV testing in a transgender and gender diverse population assigned female at birth: comfort, difficulty, and willingness to use.

Background: Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face numerous barriers to preventive care, including for HPV and cervical cancer screening. Self-sampling options may expand access to HPV testing for TGD people AFAB. Methods: We recruited TGD individuals AFAB to collect cervicovaginal and anal specimens at-home using self-sampling for HPV testing, and individuals reported their perceptions of self-sampling. Associations between demographic and health characteristics and each of comfort of use, ease of use, and willingness to use self-sampling were estimated using robust Poisson regression. Results: The majority of the 101 participants who completed the study reported that the cervicovaginal self-swab was not uncomfortable (68.3%) and not difficult to use (86.1%), and nearly all (96.0%) were willing to use the swab in the future. Fewer participants found the anal swab to not be uncomfortable (47.5%), but most participants still found the anal swab to not be difficult to use (70.2%) and were willing to use the swab in the future (89.1%). Participants were more willing to use either swab if they had not seen a medical professional in the past year. About 70% of participants who reported negative experiences with either self-swab were still willing to use that swab in the future. Conclusions: TGD AFAB individuals were willing to use and preferred self-sampling methods for cervicovaginal and anal HPV testing. Developing clinically approved self-sampling options for cancer screening could expand access to HPV screening for TGD AFAB populations.

Patterns of poly tobacco use among adults in the Population Assessment of Tobacco and Health (PATH) study, 2013-2017: a multistate Markov transition analysis.

BACKGROUND: A better understanding of sociodemographic transition patterns between single, dual and poly tobacco product use may help improve tobacco control policy interventions. METHODS: HRs of transition between never, non-current (no past 30-day use), cigarette, e-cigarette, other combustible, smokeless tobacco (SLT), dual and poly tobacco use states in adults were estimated for age, sex, race/ethnicity, education and income using a multistate model for waves 1-4 of the Population Assessment of Tobacco and Health study (2013-2017), a US-based cohort study, accounting for complex survey design. RESULTS: Sole cigarette and SLT use were persistent, with 77% and 78% of adults continuing use after one wave. Other use states were more transient, with 29%-48% of adults reporting the same pattern after one wave. If single-product users transitioned, it was most likely to non-current use while dual or poly cigarette users were most likely to transition to exclusive cigarette use. Males were more likely than females to initiate combustible product use after a history of no use, and after a period of tobacco use cessation. Hispanic and non-Hispanic black participants initiated cigarette use at higher rates than non-Hispanic white participants, and had higher rates of experimentation with tobacco products between study waves. Lower socioeconomic status was associated with higher rates of transition into combustible tobacco use. CONCLUSIONS: Dual and poly tobacco use is largely transient, while single-use patterns are more stable over time. Transitions differ by age, sex, race/ethnicity, education and income, which may influence the impact of current and future tobacco control efforts.

Changing patterns of cigarette and ENDS transitions in the USA: a multistate transition analysis of youth and adults in the PATH Study in 2015-2017 vs 2017-2019.

INTRODUCTION: It is unknown how recent changes in the tobacco product marketplace have impacted transitions in cigarette and electronic nicotine delivery system (ENDS) use. METHODS: A multistate transition model was applied to 24 242 adults and 12 067 youth in waves 2-4 (2015-2017) and 28 061 adults and 12 538 youth in waves 4 and 5 (2017-2019) of the Population Assessment of Tobacco and Health Study. Transition rates for initiation, cessation and product transitions were estimated in multivariable models, accounting for gender, age group, race/ethnicity and daily versus non-daily product use. RESULTS: Changes in ENDS initiation/relapse rates depended on age, including among adults. Among youth who had never established tobacco use, the 1-year probability of ENDS initiation increased after 2017 from 1.6% (95% CI 1.4% to 1.8%) to 3.8% (95% CI 3.4% to 4.2%). Persistence of ENDS-only use (ie, 1-year probability of continuing to use ENDS only) increased for youth from 40.7% (95% CI 34.4% to 46.9%) to 65.7% (95% CI 60.5% to 71.1%) and for adults from 57.8% (95% CI 54.4% to 61.3%) to 78.2% (95% CI 76.0% to 80.4%). Persistence of dual use similarly increased for youth from 48.3% (95% CI 37.4% to 59.2%) to 60.9% (95% CI 43.0% to 78.8%) and for adults from 40.1% (95% CI 37.0% to 43.2%) to 63.8% (95% CI 59.6% to 67.6%). Youth and young adults who used both products became more likely to transition to ENDS-only use, but middle-aged and older adults did not. CONCLUSIONS: ENDS-only and dual use became more persistent. Middle-aged and older adults who used both products became less likely to transition to cigarette-only use but not more likely to discontinue cigarettes. Youth and young adults became more likely to transition to ENDS-only use.

Associations of Demographics, Dependence, and Biomarkers With Transitions in Tobacco Product Use in a Cohort of Cigarette Users and Dual Users of Cigarettes and E-cigarettes.

INTRODUCTION: It is uncertain whether e-cigarettes facilitate smoking cessation in the real world. We aimed to understand whether and how transitions among cigarette, e-cigarette, and dual use are associated with sociodemographics, dependence measures, and biomarkers. AIMS AND METHODS: We followed 380 adult daily cigarette users and dual users every 2 months for up to 2 years. We estimated transition rates between noncurrent, cigarette-only, e-cigarette-only, and dual use states using a multistate transition model. We estimated univariable hazard ratios (HR) for demographics, dependence measures for cigarettes and e-cigarettes, biomarkers, spousal or partner behaviors, and other measures. RESULTS: We estimated that participants transitioned from cigarette-only to e-cigarette-only through a period of dual use. Dual users ceased smoking (transitioning to e-cigarette-only use) at a greater rate than cigarette-only users did (HR 2.44, 95% CI: 1.49, 4.02). However, of the 60% of dual users estimated to transition to single product use in 1 year, 83% would transition to cigarette-only use and only 17% to e-cigarette-only use. E-cigarette dependence measures were generally associated with reduced e-cigarette cessation rather than enhanced cigarette cessation. E-cigarette users motivated by harm or toxicity reduction or because of restrictions on where or when they could smoke had reduced rates of smoking relapse. Cigarette dependence and spousal smoking were barriers to cigarette cessation for dual users, while using e-cigarettes first in the morning, motivation to quit smoking, and sensory, social, and emotional enjoyment of e-cigarettes (secondary dependence motives) were facilitators of smoking cessation among dual users. CONCLUSIONS: Tobacco control policy and interventions may be informed by the barriers and facilitators of product transitions. IMPLICATIONS: Although e-cigarettes have the potential to promote smoking cessation, their real-world impact is uncertain. In this cohort, dual users were more likely to quit smoking than cigarette-only users, but the overall impact was small because most dual users returned to cigarette-only use. Moreover, e-cigarette dependence promoted continued dual use rather than smoking cessation. Yet, high motivation to quit smoking and the sensory, social, and emotional enjoyment of e-cigarettes facilitated smoking cessation in dual users. Better understanding the barriers and facilitators of transitions can help to develop regulations and interventions that lead to more effective use of e-cigarettes for smoking cessation.

Public health impact of a US ban on menthol in cigarettes and cigars: a simulation study.

INTRODUCTION: The US Food and Drug Administration most recently announced its intention to ban menthol cigarettes and cigars nationwide in April 2021. Implementation of the ban will require evidence that it would improve public health. This paper simulates the potential public health impact of a ban on menthol in cigarettes and cigars through its impacts on smoking initiation, smoking cessation and switching to nicotine vaping products (NVPs). METHODS: After calibrating an established US simulation model to reflect recent use trends in cigarette and NVP use, we extended the model to incorporate menthol and non-menthol cigarette use under a status quo scenario. Applying estimates from a recent expert elicitation on the behavioural impacts of a menthol ban, we developed a menthol ban scenario with the ban starting in 2021. We estimated the public health impact as the difference between smoking and vaping-attributable deaths and life-years lost in the status quo scenario and the menthol ban scenario from 2021 to 2060. RESULTS: As a result of the ban, overall smoking was estimated to decline by 15% as early as 2026 due to menthol smokers quitting both NVP and combustible use or switching to NVPs. These transitions are projected to reduce cumulative smoking and vaping-attributable deaths from 2021 to 2060 by 5% (650 000 in total) and reduce life-years lost by 8.8% (11.3 million). Sensitivity analyses showed appreciable public health benefits across different parameter specifications. CONCLUSIONS AND RELEVANCE: Our findings strongly support the implementation of a ban on menthol in cigarettes and cigars.

Understanding the mechanisms of HPV-related carcinogenesis: Implications for cell cycle dynamics.

The role of human papillomavirus (HPV) as a causative agent for epithelial cancers is well-known, but many open questions remain regarding the downstream gene regulatory effects of viral proteins E6 and E7 on the cell cycle. Here, we extend a cell cycle model originally presented by Gérard and Goldbeter (2009) in order to capture the effects of E6 and E7 on key actors in the cell cycle. Results suggest that E6 is sufficient to reverse p53-induced quiescence, while E7 is sufficient to reverse p16INK4a-induced quiescence; both E6 and E7 are necessary when p53 and p16INK4a are both active. Moreover, E7 appears to play a role as a "growth factor substitute", inducing cell division in the absence of growth factor. Low levels of E7 may permit regular cell division, but the results suggest that higher levels of E7 dysregulate the cell cycle in ways that may destabilize the cellular genome. The mechanisms explored here provide opportunities for developing new treatment targets that take advantage of the cell cycle regulatory system to prevent HPV-related cancer effects.

Sociodemographic Survival Disparities for Lung Cancer in the United States, 2000-2016.

BACKGROUND: Understanding the impact of patient and tumor characteristics on lung cancer survival can help build personalized prognostic models and identify health disparities. METHODS: We identified 557 555 patients aged 25 years and older diagnosed with lung or bronchus carcinoma from the Surveillance, Epidemiology, and End Results database, 2000-2016. We estimated hazard ratios (HR) for demographic (sex, age, race and ethnicity), tumor (stage, histology, year of diagnosis), and geographic characteristics (census tract-level urbanicity, socioeconomic status [SES]), as well as selected interactions, on the rate of lung cancer-specific death using multivariable proportional hazards models. RESULTS: Women had a higher survival (lower hazard) of lung cancer-specific death than men (HR = 0.83, 95% confidence interval [CI] = 0.82 to 0.83). Hazards differed by race and ethnicity. Regional (HR = 2.41, 95% CI = 2.37 to 2.44) and distant (HR = 6.61, 95% CI = 6.53 to 6.69) tumors were associated with a lower survival (higher hazard) than localized tumors. Small cell tumors were associated with a lower survival (HR = 1.19, 95% CI = 1.18 to 1.20) than non-small cell tumors. Patients diagnosed after 2009 had lower hazards (HR = 0.86, 95% CI = 085 to 0.86) than those diagnosed 2000-2009. Lung cancer-specific survival did not depend on urbanicity after adjusting for census tract-level SES, but survival decreased with decreasing census tract-level SES. Differences in survival between non-Hispanic Black and White patients were greater for younger patients and localized tumors and increased with census tract-level SES. Differences by sex were greatest for young patients and localized tumors. CONCLUSIONS: Disparities in survival after lung cancer diagnosis remain, with intersectional patterns suggesting differential access to and quality of care. Efforts are needed to ensure that high-risk groups receive guideline-concordant treatment.

The Impact of Current Tobacco Product Use Definitions on Estimates of Transitions Between Cigarette and ENDS Use.

INTRODUCTION: Definitions of current tobacco and nicotine delivery product use vary and depend on frequency of use, established-use criteria, and the product type. Previous research has not considered how transition rates between current use of different products depend on the current use definition. AIMS AND METHODS: We applied a multistate transition model to data on U.S. adults from waves 1-4 (2013-2017) of the Population Assessment of Tobacco and Health (PATH) study. We estimated transition rates between never, non-current, cigarette, electronic nicotine delivery systems (ENDS), and dual use states with and without established-use criteria (has smoked 100+ cigarettes in their lifetime; ever fairly regularly used ENDS) and different frequency thresholds (1+, 10+, 20+, and 30 days of the past 30 days). We considered use below a frequency threshold as either non-current use or a distinct, infrequent use category. RESULTS: When treating use below a frequency threshold as non-current use, transition probability estimates were largely robust to the choice of use frequency threshold, although sole ENDS users were more likely to transition to non-current use or dual use as the current use threshold increased. Removing the established-use criterion for ENDS reduced the estimates of sole ENDS and dual users staying in their use state. When treating infrequent use as a separate category, transition probability estimates were dependent on the use frequency threshold, particularly transitions among the dual use states. CONCLUSIONS: Product use definitions have important implications for assessing product use transitions and thus the public health implications of cigarette and ENDS control strategies. IMPLICATIONS: How we define "current use" of tobacco and nicotine delivery products changes our estimates of how individuals transition to, between, and from different patterns of use. We show that the robustness of transition estimates to whether or not non-established users are included as current users and to different frequency-of-use threshold depends in part on whether low-frequency users are categorized as non-current users or as a distinct category. Our results emphasize the importance of intentional definitions of product use that reflect the larger goals of public health and tobacco control.

Prevalence and determinants of oral and cervicogenital HPV infection: Baseline analysis of the Michigan HPV and Oropharyngeal Cancer (MHOC) cohort study.

We determined baseline oral and cervicogenital human papillomavirus (HPV) prevalence and determinants of infection in the Michigan HPV and Oropharyngeal Cancer (MHOC) study. We enrolled 394 college-age and older participants of both sexes in Ann Arbor, Michigan and the surrounding area. All participants provided an oral sample at baseline, and 130 females provided a cervicogenital sample. Samples were tested for 18 HPV genotypes using polymerase chain reaction (PCR) MassArray. Participants filled out sociodemographic and behavioral questionnaires. Prevalence ratios for HPV oral or cervicogenital prevalence by predictor variables were estimated in univariable log-binomial models. Analysis was conducted 2018-20. In the full cohort, baseline oral HPV prevalence was 10.0% for any detected genotype (among the 338 valid oral tests at baseline) and 6.5% for high-risk types, and cervicogenital prevalence was 20.0% and 10.8%, respectively (among the 130 first valid cervicogenital tests). Oral HPV prevalence did not vary by sex, with 10.5% of women and 9.0% of men having an infection. We found a high prevalence of oral and cervicogenital HPV infection in college-age participants reporting no lifetime sexual partners. Reporting a single recent partner was associated with a lower oral HPV prevalence (PR 0.39, 95% CI: 0.16, 0.96) than reporting no recent (but at least one ever) partner. No similar protective effect was seen for cervicogenital HPV. Both oral and cervicogenital prevalence increased with the number of recent partners for most sexual behaviors. We observed an ecological fallacy masking the direction of impact of vaccination on HPV prevalence in the full cohort compared to the college-aged and the age 23+ populations considered separately. Substance use was not significantly associated with oral or cervicogenital HPV infection. Many studies report substantially higher oral HPV infection prevalence in men than in women. That difference may not be uniform across populations in the US.

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.

Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort.

BACKGROUND: Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis. OBJECTIVE: To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer. DESIGN: Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening. SETTING: Breast Cancer Surveillance Consortium (BCSC) facilities. PARTICIPANTS: Women aged 50 to 74 years at first mammography screen between 2000 and 2018. MEASUREMENTS: Screening mammograms and screen-detected or interval breast cancer. RESULTS: The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis. LIMITATIONS: Exclusion of women with first mammography screen outside BCSC. CONCLUSION: On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening. PRIMARY FUNDING SOURCE: National Cancer Institute.

Incidence and clearance of oral and cervicogenital HPV infection: longitudinal analysis of the MHOC cohort study.

OBJECTIVES: The Michigan HPV and Oropharyngeal Cancer study aimed to evaluate patterns of oral and cervicogenital human papillomavirus (HPV) infection prevalence, incidence, and clearance as well as their relationship to sexual behaviours. DESIGN: Cohort SETTING: General public in and around Ann Arbor, Michigan. PARTICIPANTS: 394 college-age and older-adult participants of both sexes provided oral samples, and 325 completed at least 2 visits. 130 who provided a cervicogenital samples, and 127 completed at least 2 visits. OUTCOMES: Incidence and clearance rates as well as HRs for oral and cervicogenital HPV. RESULTS: Oral HPV infections were transient, with only 16% of genotypes persisting to the next visit. The mean time to clearance of a genotype was 46 days (95% CI 37 to 58). In contrast, cervicogenital infections were more persistent, with 56% of genotypes persisting to the next visit. The mean time to clearance of a genotype was 87 days (95% CI 74 to 102). HPV vaccination was associated with reduced incidence of cervicogenital HPV infection (HR 0.63; 95% CI 0.47 to 0.83) but not oral HPV infection. Incidence of oral HPV infection was associated with 2+ recent deep kissing partners (HR 2.00; 95% CI 1.13 to 3.56). Incidence of both oral (HR: 1.70; 95% CI 1.08 to 2.68) and cervicogenital (HR 2.46; 95% CI 1.69 to 3.59) was associated with 2+ recent sexual partners. CONCLUSIONS: Detection of oral HPV was highly transient, but incidence was associated with recent deep kissing and sexual partners. Detection of cervicogenital HPV was more persistent, and incidence was positively associated with recent sexual partners and negatively associated with HPV vaccination.

Scalable proximal methods for cause-specific hazard modeling with time-varying coefficients.

Survival modeling with time-varying coefficients has proven useful in analyzing time-to-event data with one or more distinct failure types. When studying the cause-specific etiology of breast and prostate cancers using the large-scale data from the Surveillance, Epidemiology, and End Results (SEER) Program, we encountered two major challenges that existing methods for estimating time-varying coefficients cannot tackle. First, these methods, dependent on expanding the original data in a repeated measurement format, result in formidable time and memory consumption as the sample size escalates to over one million. In this case, even a well-configured workstation cannot accommodate their implementations. Second, when the large-scale data under analysis include binary predictors with near-zero variance (e.g., only 0.6% of patients in our SEER prostate cancer data had tumors regional to the lymph nodes), existing methods suffer from numerical instability due to ill-conditioned second-order information. The estimation accuracy deteriorates further with multiple competing risks. To address these issues, we propose a proximal Newton algorithm with a shared-memory parallelization scheme and tests of significance and nonproportionality for the time-varying effects. A simulation study shows that our scalable approach reduces the time and memory costs by orders of magnitude and enjoys improved estimation accuracy compared with alternative approaches. Applications to the SEER cancer data demonstrate the real-world performance of the proximal Newton algorithm.

The Impact of Menthol Cigarette Flavor in the U.S.: Cigarette and ENDS Transitions by Sociodemographic Group.

INTRODUCTION: A better understanding of how menthol cigarette flavoring and ENDS impact smoking initiation, cessation, and transitions between tobacco products could help elucidate the potential impact of a U.S. menthol ban on combustible tobacco products. METHODS: A multistate transition model was applied to data on 23,232 adults from Waves 1-4 (2013-2017) of the Population Assessment of Tobacco and Health Study (analysis was conducted in 2020-2021). Transition rates among never, noncurrent, nonmenthol versus menthol cigarette, ENDS, and dual everyday/someday use were estimated, as were transition-specific hazard ratios for age, sex, race/ethnicity, education, and income. RESULTS: Non-Hispanic Blacks who smoked menthol discontinued smoking at a much lower rate than those who smoked nonmenthol (hazard ratio=0.43, 95% CI=0.29, 0.64), but there was no statistically significant difference in the discontinuation rates among non-Hispanic Whites (hazard ratio=0.97, 95% CI=0.80, 1.16) or Hispanics (hazard ratio=0.81, 95% CI=0.56, 1.16). Non-Hispanic Whites who smoked menthol were more likely to become dual users than those who smoked nonmenthol (hazard ratio=1.43, 95% CI=1.14, 1.80). Young adults initiated menthol smoking at a higher rate than older adults (age 18-24 years versus ≥55 years: hazard ratio=2.45, 95% CI=1.44, 4.15) but not nonmenthol smoking (hazard ratio=1.02, 95% CI=0.62, 1.69). There were differences by sex in the impact of menthol flavor on smoking initiation and discontinuation but little difference by education or income. CONCLUSIONS: Sociodemographic differences in product transitions should be accounted for when estimating the potential impact of a menthol ban.

Latent class analysis of use frequencies for multiple tobacco products in US adults.

A persistent challenge is characterizing patterns of tobacco use in terms of product combinations and frequency. Using Wave 4 (2016-17) Population Assessment of Tobacco and Health Study adult data, we conducted latent class analyses (LCA) of past 30-day frequency of use for 9 tobacco products. One-step LCA with joint multinomial logistic regression models compared sociodemographic factors between users (n = 13,716) and non-users (n = 17,457), and between latent classes of users. We accounted for survey design and weights. Our analyses identified 6 classes: in addition to non-users (C0: 75.7%), we found 5 distinct latent classes of users: daily exclusive cigarette users (C1: 15.5%); occasional cigarette and polytobacco users (C2: 3.8%); frequent e-product and occasional cigarette users (C3: 2.2%); daily smokeless tobacco (SLT) and infrequent cigarette users (C4: 2.0%); and occasional cigar users (C5: 0.8%). Compared to C1: C2 and C3 had higher odds of being male (versus female), younger (especially 18-24 versus 55 years), and having higher education; C2 had higher, while C3 and C4 had lower, odds of being a racial/ethnic minority (versus Non-Hispanic White); C4 and C5 had much higher odds of being male (versus female) and heterosexual (versus sexual minority) and having higher income; and C5 had higher odds of college or more education. We identified three classes of daily or frequent users of a primary product (cigarettes, SLT or e-products) and two classes of occasional users (cigarettes, cigars and polytobacco). Sociodemographic differences in class membership may influence tobacco-related health disparities associated with specific patterns of use.