Biography

Dr. Wentzensen received an M.D. from the University of Heidelberg in 2000. He trained in General Surgery and conducted research in Surgical Oncology at the Department of Surgery, University of Heidelberg from 2000-2002. From 2002-2007, Dr. Wentzensen did his Ph.D. (Habilitation) in Applied Tumor Biology at the Institute of Pathology, University of Heidelberg. During this time, he conducted research in molecular biology, molecular pathology, and molecular epidemiology of cervical cancer. He built a research group focusing on cervical cancer biomarker discovery and validation and established a diagnostic laboratory for cervical cancer screening. From 2005-2007, he did a Master of Epidemiology at the University of Mainz. In 2007, Dr. Wentzensen joined DCEG as a visiting fellow. Dr. Wentzensen’s research is focused on etiologic heterogeneity and biomarker discovery of gynecological cancers, mainly cervical and ovarian. His research has been highly recognized internationally. His medical doctorate thesis on human papillomavirus integration was awarded summa cum laude. He has received multiple research awards from the University of Heidelberg and several awards for presentations at international scientific meetings, including an AACR scholar in training award. He received a competitive stipend supporting a 2-year visiting fellowship at the NCI. During his time at DCEG, he won two intramural research awards (IRA). He was selected as an expert for the Cochrane Gynaecological Cancer Review Group (Section ‘Prevention of Cervical Cancer’) and the Society of Gynecologic Oncologists Future Strategies of Cervical Cancer Prevention Meeting.

Research Interests

I want to apply my broad knowledge of tumor biology in molecular epidemiologic studies of gynecological cancers. I have special expertise in the p16/Rb pathway, human papillomavirus biology, gene methylation, and molecular profiling of cancers. I am currently working on several established DCEG studies, including the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED) and the Polish Ovarian Cancer Case Control Study. I have just initiated a new field effort to analyze the etiology of cervical precancers and to improve colposcopy-biopsy protocols (Study to Distinguish HPV Infection from Cervical Precancer, Biopsy Study).

Cervical Cancer

Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED): I am Co-Project Officer of the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED, PI: Sophia Wang). Accrual of the main part of SUCCEED has been completed and more than 2000 frozen tissues have been collected from women with HPV infection, precancer, and cancer. I am conducting several profiling studies in tissue from all steps of cervical cancer progression, including mRNA profiling, microRNA profiling, methylation profiling, viral genotyping, and viral gene expression profiling to elucidate the transitions from HPV infection to precancer and from precancer to invasive cancer.

Study to Distinguish HPV Infection from Cervical Precancer (Biopsy Study): Colposcopy guided biopsy procedures are imprecise, heterogeneous, and frequently miss the worst lesion present on the cervix. This leads to misclassification of disease in epidemiological studies and complicates clinical management of women with abnormal screening results. To address this problem, we have designed and launched a new field effort, the Study to Distinguish HPV Infection from Cervical Precancer (Biopsy Study). We are using a multiple-biopsy protocol with digital documentation of colposcopic impression and biopsy sites to link findings on the lesion level with colposcopic appearance and worst disease identified. This study gives important insight into the etiology and heterogeneity of cervical precancer, allows studying the clonal relationship of multiple lesions on the cervix, and will improve colposcopy-biopsy protocols. The study is conducted in close collaboration with the American Society of Colposcopy and Cervical Pathology and will provide important scientific input to improve clinical management.

Other Studies of HPV-related cancers: I am a major collaborator on two new HREB efforts, the Nigerian Cervical Cancer Screening Study and the Anal Cancer Screening Study. In both studies, I am leading biomarker and colposcopy/anoscopy components. Based on my long experience with cellular and humoral immune responses against tumor-associated and viral antigens, I am evaluating novel serologic assays to detect HPV antibodies as markers of exposure and protection together with other HREB and IIB investigators in several DCEG-based studies (Costa Rica Natural History Cohort, Costa Rica Vaccine Trial, ASCUS-LSIL-Triage-Study). I am evaluating novel biomarkers for cervical precancers in different HREB studies and collaborate with researchers in IIB on HPV-related lung and head and neck cancers.

Ovarian Cancer

The etiology of ovarian cancer is complex and poorly understood, in part because risk factor associations may differ by histological type, grade and other factors. I am conducting tissue based profiling studies in the Polish Ovarian Cancer Case Control Study, including methylation profiling and immunohistochemical staining of tissue microarrays to improve the understanding of etiologic heterogeneity. In collaboration with investigators in the Biostatistics Branch, we are extending our analyses to cases from the Surveillance, Epidemiology, and End Results Residual Tissue Repository (SEER RTR). I am analyzing several a-priori markers and pathways, such as mismatch repair deficiency, p53 and p16/Rb alterations, and telomere length alterations. We wish to identify markers that can be integrated with standardized histological typing and grading to improve the classification of ovarian tumors for epidemiologic studies. We also want to identify markers for early detection that can be translated into clinical or screening applications. In collaboration with investigators in the Clinical Genetics Branch and with outside clinical partners, we are evaluating novel techniques for sampling of endometrial and ovarian epithelium (Benign Reproductive Tissue Evaluation, BRTE, and Screening Modalities Studies).

Experimental data have demonstrated that estrogen, estrogen metabolite, and androgen exposures to ovarian epithelium promote tumor growth. The few studies that have assessed pre-diagnostic hormone levels related to ovarian cancer have produced inconclusive findings, and have been limited by experimental design and low case numbers. We are now assessing the association of endogenous androgen, estrogen, and estrogen metabolite levels in pre-diagnostic sera from women postmenopausal at blood draw using a new mass-spectrometry based assay that has been developed at an NCI-Frederick lab. Due to the low prevalence of ovarian cancer, we are pooling cases from several NCI-based and outside cohorts.

Keywords

Cervical cancer, ovarian cancer, human papillomavirus, tumor biology, etiologic heterogeneity, biomarker discovery

Selected Publications

• Katki HA, Wentzensen N. How might HPV testing be integrated into cervical screening? Lancet Oncol 2012 Jan;13(1):8-10. Epub 2011 Dec 14.
• Yang HP, Trabert B, Murphy MA, Sherman ME, Sampson JN, Brinton LA, Hartge P, Hollenbeck A, Park Y, Wentzensen N. Ovarian cancer risk factors by histologic subtypes in the NIH-AARP diet and health study. Int J Cancer 2011 Sep 29. doi:10.1002/ijc.26469. [Epub ahead of print] PubMed PMID: 21960414.
• Sahasrabuddhe VV, Luhn P, Wentzensen N. Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts. Future Microbiol 2011 Sep;6(9):1083-98. PubMed PMID: 21958146.
• Wentzensen N, Rodriguez AC, Viscidi R, Herrero R, Hildesheim A, Ghosh A, Morales J, Wacholder S, Guillen D, Alfaro M, Safaeian M, Burk RD, Schiffman M. A competitive serological assay shows naturally acquired immunity to human papillomavirus infections in the Guanacaste Natural History Study. J Infect Dis2011 Jul 1;204(1):94-102. PubMed PMID: 21628663; PubMed Central PMCID:PMC3130470.
• Schiffman M, Wentzensen N, Wacholder S, Kinney W, Gage JC, Castle PE. Human papillomavirus testing in the prevention of cervical cancer. J Natl Cancer Inst 2011 Mar 2;103(5):368-83. Epub 2011 Jan 31. Review. PubMed PMID: 21282563; PubMed Central PMCID: PMC3046952.
• Mai PL, Wentzensen N, Greene MH. Challenges related to developing serum-based biomarkers for early ovarian cancer detection. Cancer Prev Res (Phila) 2011 Mar;4(3):303-6. PubMed PMID: 21372029; PubMed Central PMCID: PMC3077065.
• Wentzensen N, Black A, Jacobs K, Yang HP, Berg CD, Caporaso N, Peters U, Ragard L, Buys SS, Chanock S, Hartge P. Genetic variation on 9p22 is associated with abnormal ovarian ultrasound results in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. PLoS One 2011;6(7):e21731. Epub 2011 Jul 7. PubMed PMID: 21750727; PubMed Central PMCID: PMC3131287.
• Murphy MA, Wentzensen N. Frequency of mismatch repair deficiency in ovarian cancer: A systematic review. Int J Cancer 2010 Dec 7. [Epub ahead of print]PubMed PMID: 21140452; PubMed Central PMCID: PMC3107885.
• Wentzensen N, Wilson LE, Wheeler CM, Carreon JD, Gravitt PE, Schiffman M, Castle PE. Hierarchical clustering of human papilloma virus genotype patterns in the ASCUS-LSIL triage study. Cancer Res 2010 Nov 1;70(21):8578-86. Epub 2010 Oct 19. PubMed PMID: 20959485; PubMed Central PMCID: PMC2970748.
• Schiffman M, Wentzensen N. From human papillomavirus to cervical cancer. Obstet Gynecol 2010 Jul;116(1):177-85. PubMed PMID: 20567185.
• Wentzensen N, Schiffman M, Dunn T, Zuna RE, Gold MA, Allen RA, Zhang R, Sherman ME, Wacholder S, Walker J, Wang SS. Multiple human papillomavirus genotype infections in cervical cancer progression in the study to understand cervical cancer early endpoints and determinants. Int J Cancer 2009 Nov1;125(9):2151-8. PubMed PMID: 19585494; PubMed Central PMCID: PMC2755508.
• Wentzensen N, Gravitt PE, Solomon D, Wheeler CM, Castle PE. A study of Amplicor human papillomavirus DNA detection in the atypical squamous cells of undetermined significance-low-grade squamous intraepithelial lesion triage study. Cancer Epidemiol Biomarkers Prev 2009 May;18(5):1341-9. Erratum in: CancerEpidemiol Biomarkers Prev. 2009 Jun;18(6):1943. PubMed PMID: 19423515; PubMed Central PMCID: PMC2804087.
• Wentzensen N, Schiffman M, Dunn ST, Zuna RE, Walker J, Allen RA, Zhang R, Sherman ME, Wacholder S, Jeronimo J, Gold MA, Wang SS. Grading the severity of cervical neoplasia based on combined histopathology, cytopathology, and HPV genotype distribution among 1,700 women referred to colposcopy in Oklahoma. Int JCancer 2009 Feb 15;124(4):964-9. PubMed PMID: 19030188; PubMed Central PMCID:PMC2796188.
• Wentzensen N, Sherman ME, Schiffman M, Wang SS. Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science. Gynecol Oncol 2009 Feb;112(2):293-9. Epub 2008 Dec 2.Review. PubMed PMID: 19054549; PubMed Central PMCID: PMC2673716.
• Cuschieri K, Wentzensen N. Human papillomavirus mRNA and p16 detection as biomarkers for the improved diagnosis of cervical neoplasia. Cancer Epidemiol Biomarkers Prev 2008 Oct;17(10):2536-45. Review. PubMed PMID: 18842994; PubMedCentral PMCID: PMC2900792.
• Wentzensen N, du Bois A, Kommoss S, Pfisterer J, von Knebel Doeberitz M, Schmidt D, Kommoss F. No metastatic cervical adenocarcinomas in a series of p16INK4a-positive mucinous or endometrioid advanced ovarian carcinomas: an analysis of the AGO Ovarian Cancer Study Group. Int J Gynecol Pathol 2008Jan;27(1):18-23. PubMed PMID: 18156969.
• Wentzensen N, Bergeron C, Cas F, Vinokurova S, von Knebel Doeberitz M. Triage of women with ASCUS and LSIL cytology: use of qualitative assessment of p16INK4a positive cells to identify patients with high-grade cervical intraepithelial neoplasia. Cancer 2007 Feb 25;111(1):58-66. PubMed PMID: 17186505.
• Wentzensen N, von Knebel Doeberitz M. Biomarkers in cervical cancer screening. Dis Markers 2007;23(4):315-30. Review. PubMed PMID: 17627065.

Collaborators

DCEG Collaborators

• William Anderson M.D., Louise Brinton Ph.D., Philip Castle Ph.D., M.P.H., Anil Chaturvedi Ph.D., Montserrat Garcia-Closas M.D., Dr.P.H., Mark Greene M.D., Allan Hildesheim PhD., James Lacey Ph.D., Mahboobeh Safaeian Ph.D., Sharon Savage M.D., Mark Schiffman M.D., M.P.H., Mark Sherman M.D., Sholom Wacholder Ph.D., Sophia Wang Ph.D.

Other NCI Collaborators

• Rodney Long M.A., Paul Meltzer, Ph.D.

Other Scientific Collaborators

• Marc Arbyn M.D., Scientific Institute of Public Health, Brussels
• Kate Cuschieri Ph.D., University of Edinburgh
• Michael Gold M.D., University of Vanderbilt
• Niels Grabe Ph.D., University of Heidelberg
• Richard Guido M.D., University of Pittsburgh
• Matthias Kloor M.D., University of Heidelberg
• Magnus von Knebel Doeberitz M.D., Ph.D., University of Heidelberg
• Michael Pawlita M.D., German Cancer Research Center
• Karl Podratz M.D., Ph.D. Mayo Clinic
• Miriam Reuschenbach M.D., University of Heidelberg
• Joan Walker M.D., University of Oklahoma
• Rosemary Zuna M.D., University of Oklahoma