Studies of Rare Cancers

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Primary liver cancer, composed of two major histologic types, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the sixth most frequently occurring cancer in the world and the second most common cause of cancer mortality. While over 80% of liver cancers occur in Asia and sub-Saharan Africa, incidence has been increasing in low-rate areas, such as the U.S. and Europe, for several decades. Our research has been focusing on identifying factors associated with this increase in incidence. While excessive alcohol consumption and hepatitis C virus infection are major risk factors, our research has found that the risk attributable to diabetes and obesity is greater than the risk attributable to other factors. To follow-up on these findings, we are examining the contributions of these factors in 2 U.S. based research studies. We are also examining whether medications such as anti-diabetic drugs, non-steroidal anti-inflammatory drugs and statins affect the risk of liver cancer in developed countries.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 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), a cross-sectional assessment on 363 HIV-positive MSM 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.