Clinical Epidemiology Unit Research Areas

Investigators in the Clinical Epidemiology Unit conduct etiologic research with potential clinical and public health applications. The CEU leads studies evaluating population-based risk prediction, early detection, and cancer prevention strategies in a number of malignancies.

Researchers in the CEU study natural history and carcinogenesis of HPV-related cancers to inform important clinical and public health questions. The focus of the etiologic efforts is on understanding the transitions from HPV infection to precancer and from precancer to invasive cancer. The understanding of natural history and carcinogenesis has led to several novel technology developments, which CEU researchers have led or collaborated on. With the increasing introduction of HPV testing in primary screening, the need arises to find accurate and objective triage strategies to determine who among the HPV-positive women needs further diagnostic evaluation or treatment. In the CEU, several new assays addressing this problem for high- and low resource settings have been developed and are being evaluated in large population-based studies. The Moonshot Initiative to “Accelerate Control of Cervical Cancer” is developing strategies to combine novel approaches to screening with HPV vaccination tailored to the needs of high- and low-resource settings.

Enduring Consensus Cervical Cancer Screening and Management Guidelines

A process to provide regular updates to the 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors

Studies of HPV-related Anogenital Cancers

Endometrial Cancer

Researchers in the CEU use various studies and approaches to evaluate etiology, risk assessment, and early detection strategies for endometrial cancer. Endometrial cancer incidence and mortality have been increasing worldwide over the past decade, yet early detection strategies for endometrial cancer are lacking. Using several study designs in diverse populations, we conduct integrated analyses of biomarkers, epidemiologic risk factors, and clinical test results among women at high risk for endometrial cancer (e.g., those postmenopausal bleeding and/or endometrial hyperplasia) to inform clinical decision-making and improve early detection of endometrial cancer. A particular focus of our research involves the evaluation of novel sampling strategies, such as vaginal tampons, which could offer minimally invasive and cost-effective diagnostic options in order to improve early detection without causing undue morbidity and cost among patients with low risk.

A black woman patient reviews results with a doctor.

Uterine Cancer Death Rates Rising, Highest Among Black Women

Increasing death rates are related to the rising incidence of aggressive subtypes of uterine cancer.

Studies of Endometrial Cancer

Consortia Studying Endometrial Cancer

Epidemiology of Endometrial Cancer Consortium (E2C2) – The E2C2 is an NCI-supported consortium dedicated to studying the etiology of this common cancer by collaboration among investigators and combination of data across studies.

Ovarian Cancer

Researchers in the CEU study the etiologic heterogeneity and risk prediction of ovarian cancer. There is increasing evidence that epithelial ovarian cancers are a group of etiologically distinct diseases that all manifest on the ovaries, in the fallopian tubes, or in the peritoneum. CEU researchers conduct studies to evaluate etiologic heterogeneity of ovarian cancer, using different approaches to differentiate subtypes, such as morphology, tumor fatality, and molecular classification. Ovarian cancer is rare in the population and typically is diagnosed at advanced disease stages. Large screening trials have not shown a meaningful survival benefit of current ovarian cancer screening approaches. CEU researchers study approaches to ovarian cancer risk prediction, using risk factors, genetics, and biomarkers in population studies.

Studies of Ovarian Cancer

Consortia Studying Ovarian Cancer

Ovarian Cancer Cohort Consortium (OC3) – The OC3 was initiated by researchers from CEU together with extramural collaborators. It is a consortium of over 25 prospective cohort studies with over 8,000 ovarian cancer endpoints that allow studies of etiologic heterogeneity and risk prediction.
Ovarian Cancer Association Consortium (OCAC) – OCAC was initially established as a consortium of case-control studies, clinical studies, and cohort studies to study genetic association with ovarian cancer. From there, OCAC has developed to conduct important efforts on epidemiological risk factors and tissue-based work.

Oropharyngeal Cancer

Human papillomavirus (HPV) has emerged as a major etiologic factor for oropharyngeal cancers, whose incidence has increased substantially since the 1990s in the United States. Today, over 70% of the annual US burden of oropharyngeal cancers is caused by HPV, with the vast majority attributable to HPV16.

CEU research addresses the molecular epidemiology and natural history of oral HPV infection and HPV-positive oropharyngeal cancer, development and validation of risk prediction models, and strategies for primary prevention through prophylactic HPV vaccination and secondary prevention and early detection through screening.

Studies of Oropharyngeal Cancer

Cancer Registry Studies: Descriptive and Molecular Epidemiology of Oropharyngeal Cancers
NHANES: Epidemiology of Oral HPV Infection
Natural History Modeling through Microsimulation
Risk Prediction

Oral Cavity Cancer

Cancers of the oral cavity (lip, oral tongue, gum, floor of mouth, palate, and buccal mucosa) are promising candidates for early detection and secondary prevention given the amenability for visual inspection and the availability of recognized precursor lesions, defined clinically and histologically. Yet, there are currently no guidelines for screening, treatment, or clinical follow-up of patients with oral cancer precursor lesions due to several knowledge gaps.

CEU research addresses key questions pertaining to the natural history of oral cancer precursor lesions, epidemiologic and molecular predictors of progression of precursor lesions to cancer, methods for screening of oral cancer precursors, and the development of oral cancer risk stratification tools. Studies are aimed to answer foundational questions pertaining to screening and early detection—who to screen (through etiologic work and risk prediction), how to screen (through evaluations of visualization adjunctions and discovery and validation of biomarkers), how to clinically manage screen-positive individuals should be clinically managed (through characterization of the natural history), and if and how population-wide screening should be conducted (through evaluations of the efficacy and effectiveness of screening).

Studies of Oral Cancer

Etiologic Studies of Head and Neck Cancers
Characterization of the Oral Microbiome in the US population
Natural History of Oral Cancer Precursors: A Prospective Cohort Study in Taiwan
Epidemiologic and Molecular Predictors of Progression of Oral Precancer to Cancer in Kaiser Permanente of Northern California
Evaluation of Adjunctive Tools for the Identification of Oral Precancer: A Community-based Cross-sectional Study in Assam, India
Somatic Mutations in Oral Rinses and Prospective Risk of Head and Neck Cancers in Five US Cohorts
Genomic Characterization of Oral Precancer and Cancer in India

Lung Cancer

Lung cancer is the most common malignancy, with an estimated 1.6 million annual incident cases worldwide and 230,000 cases in the United States. Cigarette smoking is the predominant risk factor, accounting for 80 to 90 percent of all lung cancers. Yet, smoking is neither necessary nor sufficient for lung cancer, underscoring the role of additional factors in lung carcinogenesis.

CEU research addresses the role of chronic inflammation in the etiology of lung cancer, through the identification of the inflammation mediators and pathways involved in lung carcinogenesis. This work is conducted through the measurement of circulating immune/inflammation marker levels in case-control studies nested within large prospective cohorts.

CEU research also focuses on the development, validation, and application of lung cancer risk stratification tools. Studies address 1) the potential utility of lung cancer risk prediction models to improve the population-level effectiveness of low-dose computed tomography (LDCT) screening in the United States and 2) discovery and validation of minimally invasive lung cancer biomarkers for improved risk stratification.

Studies of Lung Cancer

Nested case-control studies within PLCO
Risk stratification and biomarker studies