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Objective We conducted a baseline study of human papillomavirus (HPV) type prevalence in invasive cervical cancers (ICC) using data from seven cancer registries (CR) in the US. Cases were diagnosed between 1994 and 2005, before the implementation of the HPV vaccines. Materials and Methods CRs from Florida, Kentucky, Louisiana, Michigan, Hawaii, Iowa and Los Angeles, California identified eligible ICC cases, and obtained sections from representative blocks of archived tumor specimens for DNA extraction. All extracts were assayed by Linear Array and if inadequate or HPV negative, re-tested with INNO-LiPA Genotype test. Clinical and demographic factors were obtained from the CRs and merged with the HPV typing data to analyze factors associated with different types and with HPV negativity. Results A total of 777 ICCs were included in this analysis, with broad geographic, age and race distribution. Overall, HPV was detected in 91% of cases, including 51% HPV16, 16% HPV18 (HPV16 negative), and 24% other oncogenic and rare types. After HPV16 and 18, the most common types were 45, 33, 31, 35 and 52. Older age and non-squamous histology were associated with HPV negative typing. Conclusions This study provides baseline pre-vaccine HPV types for post-vaccine ICC surveillance in the future. HPV16 and/or 18 were found in 67% of ICCs, indicating the potential for vaccines to prevent a significant number of cervical cancers.

Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of β-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of β-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited β-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggest that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/β-catenin signaling pathway.