Annals of Epidemiology

Cigarette smoking in relation to survival in Black women with ovarian cancer: Evidence from the African American Cancer Epidemiology Study (AACES)

Numerous studies have documented the negative impact of cigarette smoking on ovarian cancer survival, but the participants in these prior studies were predominantly White women. In comparison, Black women experience significantly worse ovarian cancer survival, which may be due in part to dissimilar risk factor profiles or factors associated with survival. We therefore examined the association between cigarette smoking and survival in a cohort of Black women with ovarian cancer. This study included participants in the multi-site population-based African American Cancer Epidemiology Study (AACES), a prospective cohort study of 592 Black women with epithelial ovarian cancer followed up for an average of 5.5 years. Cox proportional hazards models were fit to estimate the association between cigarette smoking status (current and former smoking vs. never smoking) and all-cause mortality adjusting for sociodemographic, lifestyle, and clinical factors. Compared with women who never smoked cigarettes, women who currently smoked cigarettes experienced worse, but not statistically significant, survival (HR 1.41; 95 % CI 0.95- 2.10), whereas women who had quit smoking had comparable survival (HR 1.06; 95 %CI 0.82-1.35). Among former smokers, the association among those who quit smoking within the past five years was of similar magnitude as for current smoking (HR 1.37; 95 % CI 0.97-1.94) but no risk was observed among those who quit for > 5 years. Black women with epithelial ovarian cancer who were current smokers experienced worse survival than those who never smoked cigarettes. Even though this association was not statistically significant, the magnitude of the association is similar to prior studies comprised predominantly of White women. Ensuring access to evidence-based smoking cessation strategies represents a potential avenue for reducing mortality in Black women with ovarian cancer.

The role of multiple mediation with contextual neighborhood measures in ovarian cancer survival

Mediation by multiple agents can affect the relation between neighborhood deprivation and segregation indices and ovarian cancer survival. In this paper, we examine a variety of potential clinical mediators in the association between deprivation indices (DIs) and segregation indices (SIs) with all-cause survival among women with ovarian cancer in the African American Cancer Epidemiology Study (AACES). We use novel Bayesian multiple mediation structural models to assess the joint role of mediators (stage at diagnosis, histology, diagnostic delay) combined with the DIs and SIs (Yost, ADI, Kolak's URB, ICE-income) and a set of confounders with survival. The confounder set is selected in a preliminary step, and each DI or SI is included in separate model fits. When multiple mediators are included, the total impact of DIs and SIs on survival is much reduced. Unlike the single mediator examples previously reported, the Yost, ADI and ICE-income indices do not display significant direct effects. This suggests that when important clinical mediators are included, the impact of neighborhood SES indices is significantly attenuated. It is also clear that certain behavioral and demographic measures such as physical activity, smoking, or adjusted family income do not have a significant role in survival when mediated by clinical factors. Multiple mediation via clinical and diagnostic-related measures reduces the contextual effects of neighborhood measures on ovarian cancer survival. The robust association of the Kolak URB index on survival may be due to its relevance to access to care, unlike SES-based indices whose impact was significantly reduced when important clinical mediators were included.

Spatial analysis of HPV infection and contextual factors associated with higher HPV prevalence

To identify areas with high rates of high-risk Papillomavirus (hrHPV) infection and associated contextual factors in the Centre Region of Portugal at the municipality level. We conducted an ecological study in 78 municipalities located in the Central Region of Portugal from March 2019 to December 2022. We used data from the cervical cancer screening (CCS) program database after switching to primary HPV testing. Demographic, socio-economic, and healthcare availability variables were extracted from official sources (Statistics Portugal and Central Region Health Administration Information Systems). Spatial analysis and logistic generalised linear models were used to identify areas of high hrHPV infection and associated contextual factors. The overall hrHPV infection prevalence was 9.9 %. We found three significant clusters, predominantly in municipalities near major urban centres. These clusters were characterised by higher population density, a greater proportion of younger women, higher median income per inhabitant, a larger proportion of residents with graduate degrees, and increased availability of healthcare units. This study has uncovered the geographical distribution of hrHPV infection at the municipal level and highlights the contextual factors associated with higher prevalence. Identifying demographics and socio-economic predictors of high hrHPV infection could support public health programs by targeting interventions to specific populations and contexts. This might open up new scenarios for improving prevention and control strategies, offering more intensive screening in areas with the most urgent needs.

Association of partner vasectomy, depot medroxyprogesterone acetate and intrauterine contraceptive devices with ovarian cancer

To assess the associations between ovarian cancer and depot medroxyprogesterone acetate (DMPA), intrauterine contraceptive devices (IUDs), and partner vasectomy. We undertook a New Zealand-wide population-based case-control study. During 2013-2015, 205 eligible cases were identified from the cancer registry (152 [74%] participated) and 1,735 eligible controls were randomly selected from the electoral roll (837 [48%] participated). A postal questionnaire was used to gather information. Ever-use of vasectomy was inversely associated with ovarian cancer in age-adjusted analysis, but not in multivariable analysis (OR = 0.67, 95% CI = 0.46-0.96, and OR = 0.82; 95% CI = 0.54-1.23, respectively). A suggestive trend towards lower risk with longer duration of reliance on partner vasectomy was observed (P-trend = 0.08). Ever-use and duration of use of DMPA were not associated with ovarian cancer. Although ever-use of IUDs was not associated with ovarian cancer, duration of use of IUDs was associated with higher risk (P-trend = 0.04). There were also statistically significant inverse associations between ovarian cancer and use of oral contraceptives, parity, and breastfeeding. Prolonged use of IUDs may increase the risk of ovarian cancer. It is also possible that an inverse association exists between ovarian cancer and partner vasectomy.

Screening learning module: Huang et al (2025), association between screening history and prognosis of cervical carcinoma in situ and invasive cervical cancer – A population-based cohort study

Educational Engagement Modules (EEMs) are teaching materials for educators and students that facilitate a deeper understanding of key epidemiological methods and concepts. Each EEM poses a series of questions using a recently published paper in Annals to further understanding of a specific study design and to encourage critical thinking and careful evaluation. This EEM focuses on cancer screening and references the following article: Huang CS, Hsiao BY, Wu MH, Chiang CJ, Hsieh PC, Chen MJ, Cheng WF, Lee WC. Association between screening history and prognosis of cervical carcinoma in situ and invasive cervical cancer: A population-based cohort study. Ann Epidemiol. 2025 Jun;106:75-81. doi: 10.1016/j.annepidem.2025.04.015. Epub 2025 May 3. PMID: 40324609 [1].

Deprivation and segregation in ovarian cancer survival among African American women: a mediation analysis

Deprivation and segregation indices are often examined as possible explanations for observed health disparities in population-based studies. In this study, we assessed the role of recognized deprivation and segregation indices specifically as they affect survival in a cohort of self-identified Black women diagnosed with ovarian cancer who enrolled in the African American Cancer Epidemiology Study. Mediation analysis was used to examine the direct and indirect effects between deprivation or segregation and overall survival via a Bayesian structural equation model with Gibbs variable selection. The results suggest that high socioeconomic status-related indices have an association with increased survival, ranging from 25% to 56%. In contrast, index of concentration at the extremes-race does not have a significant impact on overall survival. In many cases, the indirect effects have very wide credible intervals; consequently, the total effect is not well estimated despite the estimation of the direct effect. Our results show that Black women living in higher socioeconomic status neighborhoods are associated with increased survival with ovarian cancer using area-level economic indices such as Yost or index of concentration at the extremes-income. In addition, the Kolak urbanization index has a similar impact and highlights the importance of area-level deprivation and segregation as potentially modifiable social factors in ovarian cancer survival.

Association between screening history and prognosis of cervical carcinoma in situ and invasive cervical cancer: A population-based cohort study

Cervical cancer remains a significant public health challenge worldwide. This study examines the impact of screening history on the prognosis of cervical carcinoma in situ and invasive cervical cancer among Taiwanese women. Data from the National Cervical Cancer Screening Registry and Taiwan Cancer Registry were analyzed, encompassing 13,552 cases of cervical carcinoma in situ and 6853 cases of invasive cervical cancer diagnosed between 2009 and 2013. The study examined the relationship between screening history and five-year cumulative probability of death using the Kaplan-Meier method and Cox regression model, adjusting for factors like age, cancer stage, histological type, urbanization level, and treatment received. Screening history was an independent prognostic factor for both invasive cervical cancer and cervical carcinoma in situ, even after adjusting for key confounders. Compared to patients diagnosed within six months of a positive screening result, those diagnosed later or with a negative screening had higher post-diagnosis mortality (adjusted hazard ratios [95 % confidence interval]: 1.42 [1.26-1.59] for invasive cervical cancer and 1.74 [0.52-5.83] for cervical carcinoma in situ), while never-screened patients had even higher mortality (1.61 [1.42-1.81] for invasive cervical cancer and 5.62 [1.29-24.51] for cervical carcinoma in situ). More advanced age at diagnosis, certain histological types, and living in less urbanized areas correlated with an increased risk of post-diagnosis death. Additionally, the absence of treatment post-diagnosis was significantly associated with worse outcomes. Screening history is a crucial independent prognostic factor for cervical carcinoma in situ and invasive cervical cancer. Patients with a recent positive screening result have a markedly better prognosis than those diagnosed later, those with negative screenings, or unscreened individuals. This study emphasizes the importance of regular and timely cervical cancer screenings in improving prognosis and underscores the need to enhance awareness and accessibility of screening programs.

Differences in cervical cancer stage at diagnosis and survival outcomes among Asian, Native Hawaiian, and other Pacific Islander patients and White patients

To explore disparities in cervical cancer diagnosis and outcomes for Asian patients and Native Hawaiian and other Pacific Islanders (NHPIs). We extracted cervical cancer patient data collected from the Surveillance, Epidemiology, and End Results 17 database. Odds ratios (ORs) for stage and time ratios (TRs) for survival outcomes were estimated using logistic regression and accelerated failure time models, respectively. Of 18770 patients, 15,847 (84.4 %) were White; 2618 (13.9 %) were Asian; and 305 (1.6 %) were NHPI. NHPI patients were less likely than White patients to be diagnosed at an early stage (adjusted OR [aOR]: 0.60; 95 % CI, 0.47-0.77), whereas Asian patients had similar stage-at-diagnosis to White patients (aOR: 0.93; 95 % CI, 0.85-1.02). Asian patients, as a group, had significantly longer overall survival (OS) (adjusted TR [aTR]: 1.46; 95 % CI, 1.33-1.61) and disease-specific survival (DSS) (aTR: 1.35; 95 % CI, 1.21-1.51) than White patients; the opposite was true for NHPIs (OS: aTR, 0.80; 95 % CI, 0.64-1.00; DSS: aTR, 0.75; 95 % CI, 0.59-0.97). We find that NHPI cervical cancer patients tend to be diagnosed later in their disease course than White patients and have shorter survival time post-diagnosis, while Asian patients tend to have longer survival time. These findings support the disaggregation of Asian and NHPI races in cervical cancer investigations.

Early adulthood overweight and obesity and risk of premenopausal ovarian cancer, and premenopausal breast cancer including receptor status: prospective cohort study of nearly 500,000 Danish women

To assess the association between higher-than-normal BMI and incidence of premenopausal ovarian and breast cancers. This prospective cohort study included 461,646 women registered in the Danish Medical Birth Registry with self-reported early adulthood BMI ≥18.5 kg/m Compared with normal weight, obesity was associated with higher rates of premenopausal ovarian cancer (HR = 1.95, 95% CI 1.19-3.21) when adjusted for parity, use of hormonal contraception, family history of ovarian and/or breast cancer, other cancer, and calendar year. Obesity was associated with lower rates of premenopausal breast cancer (HR = 0.77, 95% CI 0.68-0.87) when adjusted for parity, use of hormonal contraception, family history of ovarian and/or breast cancer, any other cancer, calendar year, smoking, and highest achieved education. The associations were strongest with estrogen receptor positive premenopausal breast cancers. Results according to HER2 status were similar to overall results for premenopausal breast cancer. Obesity was associated with higher incidence of premenopausal ovarian cancer and lower incidence of premenopausal breast cancer.

Dynamic prediction and prognostic analysis of patients with cervical cancer: a landmarking analysis approach

Providing up-to-date information on patient prognosis is important in determining the optimal treatment strategies. The currently available prediction models, such as the Cox model, are limited to making predictions from baseline and do not consider the time-varying effects of covariates. A total of 1501 cervical cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database were included. We introduced three landmark dynamic prediction models (models 1-3) that explore the dynamic effects of prognostic factors to obtain 5-year dynamic survival rate predictions at different prediction times. The performances of these models were evaluated by Harrell's C-index and the Brier score using cross-validation. Some variables did not meet the proportional hazards assumption, indicating that the constant hazard ratios were unreliable. Model 3, which showed the best performance for prediction, was selected as the final model. Significant time-varying effects were observed for age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and histological subtypes. Three patients were as examples used to illustrate how the predicted probabilities change at different prediction times during follow-up. Model 3 can effectively incorporate covariates with time-varying effects and update the probability of surviving an additional 5 years at different prediction times. The use of the landmark approach may provide evidence for clinical decision making by updating personalized information for patients.