Cutaneous squamous cell carcinoma (SCC), along with basal cell carcinoma (BCC), comprise the non-melanoma skin cancers (NMSC), the most common cancer in Caucasians, with more than 3,000,000 new cases diagnosed annually in the United States. While not usually fatal, SCC may repeatedly recur and result in death in a small proportion of patients, and a history of SCC has been consistently associated with an increased risk of several other types of cancers. Despite the current knowledge about the harms of sun exposure, and increased use of sunscreen, SCC incidence rates continue to increase, emphasizing the public health importance of this highly prevalent cancer, and highlighting the need for an increased understanding of its etiology and control. Accumulating evidence suggests that cutaneous human papillomavirus (HPV) infection may be a risk factor for developing NMSC, particularly SCC. DNA from cutaneous HPV types in multiple genera has been detected in up to 50% of SCC tissues from immuno-competent individuals. In addition, several case-control studies have demonstrated statistically significant associations between SCC and antibodies against cutaneous HPV types, presence of HPV DNA in eyebrow hair follicles or HPV DNA in normal skin samples. Tumor-based HPV DNA detection and serology measurements were incorporated into our own case-control study, in which cutaneous HPV seroreactivity was significantly associated with HPV DNA-positive SCC, with antibodies detected for the same HPV types that were present in the tumor tissue. In the same study, SCC was also associated with another cutaneous virus, Merkel cell polyomavirus (MCV), with MCV DNA-positive cases having significantly higher MCV antibody levels than controls. Although the case-control data are highly compelling, causal associations between cutaneous papillomavirus and polyomavirus infections cannot be established in the absence of prospective data that clearly demonstrate the presence of the viral infections prior to the onset of disease. We propose to conduct a prospective cohort study of individuals at risk for SCC, obtaining multiple biospecimens for the measurement of cutaneous HPV and MCV infections, and following participants for up to four years, conducting full body skin exams for the detection of incident SCC. The goal of the proposed research is to estimate the risk of SCC associated with cutaneous HPV and MCV infections and to demonstrate type-specific concordance between viral infections in normal tissues and subsequent NMSC lesions. The proposed study would provide the critical evidence needed for establishing causality between cutaneous viral infections and SCC.

Public Health Relevance

We hypothesize that an increased risk of squamous cell carcinoma (SCC) will be observed among individuals infected with cutaneous HPV and MCV, and that the same viral types present in normal tissues will be detected in the subsequent SCC tumors. The proposed study would provide the critical temporal evidence for the design and eventual implementation of potential vaccination strategies aimed at reducing incidence of SCC.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA168536-02
Application #
8754425
Study Section
Special Emphasis Panel (ZCA1-RPRB-M)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
$312,873
Indirect Cost
$127,192
Name
H. Lee Moffitt Cancer Center & Research Institute
Department
Type
DUNS #
139301956
City
Tampa
State
FL
Country
United States
Zip Code
33612
Prieto-Granada, Carlos; Castner, Nicholas; Chen, Ann et al. (2018) Behavior of Cutaneous Adnexal Malignancies: a Single Institution Experience. Pathol Oncol Res :
Abate-Daga, Daniel; Ramello, Maria C; Smalley, Inna et al. (2018) The biology and therapeutic management of melanoma brain metastases. Biochem Pharmacol 153:35-45
Konno, Hiroyasu; Yamauchi, Shota; Berglund, Anders et al. (2018) Suppression of STING signaling through epigenetic silencing and missense mutation impedes DNA damage mediated cytokine production. Oncogene 37:2037-2051
Eroglu, Zeynep; Ozgun, Alpaslan (2018) Updates and challenges on treatment with BRAF/MEK-inhibitors in melanoma. Expert Opin Orphan Drugs 6:545-551
Zhu, Genyuan; Brayer, Jason; Padron, Eric et al. (2018) OMIP-049: Analysis of Human Myelopoiesis and Myeloid Neoplasms. Cytometry A 93:982-986
Zhu, Genyuan; Nemoto, Satoshi; Mailloux, Adam W et al. (2018) Induction of Tertiary Lymphoid Structures With Antitumor Function by a Lymph Node-Derived Stromal Cell Line. Front Immunol 9:1609
Ramello, Maria C; Haura, Eric B; Abate-Daga, Daniel (2018) CAR-T cells and combination therapies: What's next in the immunotherapy revolution? Pharmacol Res 129:194-203
Eroglu, Zeynep; Zaretsky, Jesse M; Hu-Lieskovan, Siwen et al. (2018) High response rate to PD-1 blockade in desmoplastic melanomas. Nature 553:347-350
Phadke, Manali; Remsing Rix, Lily L; Smalley, Inna et al. (2018) Dabrafenib inhibits the growth of BRAF-WT cancers through CDK16 and NEK9 inhibition. Mol Oncol 12:74-88
Saglam, Ozlen; Naqvi, Syeda M H; Zhang, Yonghong et al. (2018) Female genitourinary tract melanoma: mutation analysis with clinicopathologic correlation: a single-institution experience. Melanoma Res 28:586-591

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