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Principal Investigator: Nicolas Wentzensen
Organization: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
Fiscal Year: 2024
Award: $535,504
Funding agency: National Cancer Institute
The following research projects are etiologic and human population based and all have various molecular components: SUCCEED directed by Dr. Wentzensen is a cross-sectional study among women referred for abnormal cevrical cancer screening results focused on the identification of biomarkers of risk at each progressive disease stage, aimed to identify the molecular events that are necessary and sufficient for progression to cervical cancer. Frozen specimens, often multiple, from 2,500 women with varying grades of cervical neoplasia (including the ectocervix, transformation zone, and endocervix) have already been collected. In a new study, the Biopsy Study conducted at the same center in Oklahoma, Dr. Wentzensen is investigating the earliest discernible transitions from HPV infection to CIN3 and the best methods for colposcopic detection of CIN3 to improve current cervical cancer prevention strategies. The ALTS clinical trial evaluated management options for women with abnormal cervical cancer screening results and has been completed several years ago. The specimens collected in women with minor cytological abnormalities and 2 year follow up still serve as an important resource to evaluate HPV tests and novel biomarkers, such as viral methylation. In the Triage of HPV-positive women Study, novel biomarkers are evaluated to decide who among HPV+/cytology- women needs referral to colposcopy. The cervical tissue immune markers study aims at evaluating various components of the cellular and humoral immune system across cervical disease stages in HIV-infected populations. The case control study of invasive cervical cancer in four Latin-American countries is an important resource to study sero-epidemiologic markers of cervical cancer risk. In the Intramural to India project, cervical cancers and its precursors are studied among HIV-infected women in India. The goal of the project is to understand the interactions between HIV and HPV at different steps in the disease process from HPV infection to precancer and cancer. Another important goal is to evaluate biomarkers for cervical precancers in HIV-infected women. Currently, there is no widely standardized approach for early detection of cervical precancers in HIV-infected populations and it is not clear whether established and novel biomarkers perform equally in HIV-infected and non-HIV-infected populations. In the Intramural to India project, we will evaluate a wide range of tests and biomarkers to evaluate risk of cervical precancer and to improve cervical cancer prevention efforts in HIV/ AIDS populations. Although HPV is implicated in over 90% of anal cancers, it is unknown if the natural history of HPV-induced anal cancer is similar to that of the cervix. There is currently no accepted method for anal cancer screening; in the absence of a standard and effective screening modality, clinicians often resort to high-resolution anoscopy, a diagnostic procedure akin to colposcopy, and directed biopsies. Anal cancer is rare in the general population but is 100 times commoner among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). The role of HIV in anal HPV natural history is not well understood and it is not clear whether the screening approaches for HIV-positive MSM need to be modified. It is crucial to better understand the natural history of HPV-related anal neoplastic disease among HIV-positive individuals to make informed decisions about secondary prevention of anal cancer. In collaboration with Kaiser Permanente Northern California, we have conducted the Anal Cancer Screening Study (ACSS) to describe the natural history of HPV and evaluate the clinical utility of various screening approaches for anal precancer detection. We have evaluated risk factors for anal HPV infection and anal precancer in this population, studied optimal sampling strategies for anal samples, showed that anal cytology is reproducible and the quality is comparable to cervical cytology, conducted modeling exercises to evaluate attribution of anal precancer to individual HPV genotypes and estimate the HPV vaccine-preventable fraction of anal precancer, and have demonstrated the accuracy and clinical utility of several biomarkers that were previously evaluated in cervical cancer screening, including HPV DNA testing with genotyping, HPV mRNA testing, and p16/Ki-67 cytology.
Terms: <AIDS><AIDS Virus><AIDS population><AIDS/HIV><Acquired Immune Deficiency><Acquired Immune Deficiency Syndrome><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome><Acquired Immunodeficiency Syndrome Virus><Active Follow-up><Anal><Anal Cancer><Anal Cancers><Anti-HIV Positivity><Anus><Anus Cancer><Biological Markers><Biopsy><Body Tissues><California><Cancers><Case-Base Studies><Case-Comparison Studies><Case-Compeer Studies><Case-Referent Studies><Case-Referrent Studies><Case/Control Studies><Causality><Cervical><Cervical Cancer><Cervical Cancer Screening><Cervical Neoplasia><Cervical Neoplasms><Cervical Tumor><Cervix><Cervix Cancer><Cervix Neoplasms><Cervix Tumor><Cervix Uteri><Cervix Uteri Neoplasm><Cervix Uteri Tumor><Clinical><Clinical Management><Clinical Trials><Collaborations><Colposcopy><Country><Cross Sectional Analysis><Cross-Sectional Analyses><Cross-Sectional Studies><Cross-Sectional Survey><Cytology><DNA><Deoxyribonucleic Acid><Detection><Diagnostic><Diagnostic Method><Diagnostic Procedure><Diagnostic Technique><Disease><Disease Frequency Surveys><Disorder><Early Diagnosis><Ectocervix><Endocervix><Etiology><Event><Exercise><Exocervix><Freezing><General Population><General Public><Genotype><Goals><HIV><HIV Positive><HIV Positivity><HIV Seroconversion><HIV Seropositivity><HIV antibody positive><HIV/AIDS><HPV><HPV 16><HPV Vaccine><HPV induced cancer><HPV infection><HPV malignancy><HPV positive><HPV(+)><HPV+><HPV+ cancer><HPV-16><HPV-Related Malignancy><HPV-associated cancer><HPV-associated malignancy><HPV-related cancer><HPV16><HTLV-III Seroconversion><HTLV-III Seropositivity><Host Factor><Host Factor Protein><Human><Human Immunodeficiency Viruses><Human Papilloma Virus><Human Papilloma Virus Vaccine><Human Papilloma Virus-Related Malignancy><Human Papilloma Virus-Related Malignant Neoplasm><Human Papilloma Virus-associated cancer><Human Papilloma Virus-associated malignancy><Human Papilloma Virus-related cancer><Human Papillomavirus><Human papilloma virus infection><Human papilloma virus type 16><Human papillomavirus 16><Human papillomavirus Vaccine><Human papillomavirus cancer><Human papillomavirus induced cancer><Human papillomavirus infection><Human papillomavirus malignancy><Human papillomavirus type 16><Human papillomavirus-Related Malignancy><Human papillomavirus-Related Malignant Neoplasm><Immune Markers><Immune system><Immunologic Markers><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><India><Individual><Infectious Human Wart Virus><Integration Host Factors><LAV-HTLV-III><Latin American><Lymphadenopathy-Associated Virus><MSM><Malignant Anal Neoplasm><Malignant Anal Tumor><Malignant Cervical Neoplasm><Malignant Cervical Tumor><Malignant Neoplasm of the Cervix><Malignant Neoplasms><Malignant Tumor><Malignant Tumor of the Anus><Malignant Tumor of the Cervix><Malignant Tumor of the Cervix Uteri><Malignant Uterine Cervix Neoplasm><Malignant Uterine Cervix Tumor><Malignant neoplasm of anus><Malignant neoplasm of cervix uteri><Messenger RNA><Methods><Methylation><Minor><Modality><Modeling><Modern Man><Molecular><Natural History><Neoplasms><Oklahoma><Persons><Population><Preventative strategy><Prevention Research><Prevention strategy><Preventive strategy><Process><Progressive Disease><R-Series Research Projects><R01 Mechanism><R01 Program><Reproducibility><Research><Research Grants><Research Project Grants><Research Projects><Research Resources><Research Specimen><Resolution><Resort><Resources><Risk><Risk Factors><Role><Sampling><Screening Result><Screening for cancer><Secondary Prevention><Seroepidemiologic Studies><Seroepidemiological Study><Sexually Transmitted Agents><Specimen><Standardization><Testing><Tissues><Triage><Uterine Cervix><Uterine Cervix Cancer><Uterine Cervix Neoplasm><Uterine Cervix Tumor><Viral><Virus-HIV><Woman><Women's study><active followup><anal squamous cell carcinoma><bio-markers><biologic marker><biomarker><biomarker identification><cancer risk><carcinogenicity><case-controlled studies><causation><cervical cancer early detection><cervical cancer prevention><cervical screening><disease causation><early cancer detection><early detection><female study><follow up><follow-up><followed up><followup><human papilloma virus 16><human papillomavirus +><human papillomavirus associated malignancy><human papillomavirus positive><human papillomavirus-associated cancer><human papillomavirus-related cancer><identification of biomarkers><identification of new biomarkers><immune suppression><immune suppressive activity><immune suppressive function><immune-based biomarkers><immunological biomarkers><immunological markers><immunosuppressive activity><immunosuppressive function><immunosuppressive response><improved><mRNA><malignancy><marker identification><men having sex with men><men who have sex with men><men who have sex with other men><neoplasia><neoplasm/cancer><neoplastic><neoplastic growth><new marker><novel biomarker><novel marker><population based><precancer><precancer cervical detection><precancerous><premalignant><presence of HPV><presence of human papillomavirus><resolutions><screening><screening cancer patients><screenings><social role><study among females><study among women><study in females><study in women><study on females><study on women><study within women><type 16 Human papilloma virus><type 16 Human papillomavirus><wart virus>