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  • Fenske, Neil A.  (6)
  • Iannacone, Michelle R.  (6)
  • Tommasino, Massimo  (6)
  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 950-950
    Abstract: Objective: Merkel cell polyomavirus (MCV) DNA has been reported previously in 0-25% of squamous cell carcinomas (SCC) occurring in immunocompetent individuals. No studies have investigated MCV seroreactivity in individuals with SCC. We conducted a clinic-based case-control study to investigate the association between MCV seroreactivity and SCC, overall and stratified by MCV DNA status of the SCC tumor tissue. Methods: Patients with histologically-confirmed cutaneous SCC (n=173) were recruited from a university dermatology clinic. Controls were patients undergoing skin cancer screening exams who screened negative for and had no history of skin or other cancers (n=300). Levels of antibodies against capsid antigens for MCV and other polyomavirus controls (JC virus (JCV) and KI virus (KIV)) were determined by fluorescent bead-based multiplex serology. Fresh-frozen tumor tissues were obtained from 145 SCC cases, and DNA from six polyomaviruses (MCV, JCV, KIV, WU virus (WUV), BK virus (BKV) and simian virus 40 (SV40)) was measured using multiplexed PCR. Polyomavirus seropositivity, based on binary cutpoints, and quartiles of seroreactivity, based on the control distribution, were compared between SCC cases and controls, overall and stratified by the presence or absence of MCV DNA in SCC tumor tissues. Associations were estimated by calculating odds ratios (OR) and 95% confidence intervals (CI) using logistic regression to adjust for age, sex, and skin reaction to the sun. Results: MCV seropositivity was associated with a statistically significant increased risk of SCC (OR=1.80, 95% CI=1.03-3.12), whereas no association was observed for JCV (OR=1.17, 95% CI=0.72-1.92) or KIV (OR=0.88, 95% CI=0.37-2.09) seropositivity. MCV DNA was detected in 55 (38%) of SCC tumor tissues, whereas all tissues were negative for DNA from the other five polyomaviruses. Using controls as the reference group, MCV DNA-positive SCC cases were three times as likely to be MCV seropositive (OR=3.15, 95% CI=1.11-8.92) and almost six times as likely to have MCV antibody levels in the fourth versus first quartile (OR=5.94, 95% CI=1.79-19.74, ptrend=0.001). No associations were observed between MCV seropositivity and MCV DNA-negative SCC (OR=1.40, 95% CI=0.78-2.77) or between JCV or KIV seropositivity and MCV DNA-negative or DNA-positive SCC. Conclusion: SCC patients were significantly more likely than controls to exhibit MCV seroreactivity, particularly if they had MCV DNA in their SCC tumor tissue. This association was specific to MCV, with no associations observed for the other polyomaviruses studied. These results suggest that past exposure to MCV may be a risk factor for SCC in immunocompetent individuals. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 950. doi:10.1158/1538-7445.AM2011-950
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 2
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 21, No. 8 ( 2012-08-01), p. 1303-1313
    Abstract: Background: Cutaneous human papillomavirus (HPV) infection may be a risk factor for squamous cell carcinoma (SCC) of the skin. Methods: To investigate the association between cutaneous HPV and SCC, a case–control study was conducted, including 173 SCC cases from a university dermatology clinic and 300 controls that screened negative for skin cancer. Serum antibodies against cutaneous HPV types in genera alpha, beta, gamma, mu, and nu were measured. Tumor tissue from 159 SCC cases was tested for the presence of DNA for genus-beta HPV types. Using logistic regression ORs and 95% confidence intervals (CI) were estimated for the associations between SCC and cutaneous HPV infection, adjusting for age and sex. The Bonferroni method was used to account for multiple comparisons. Results: SCC was positively associated with seropositivity to any genus-beta HPV type (OR, 1.93; 95% CI, 1.23–3.02), particularly with types in species-1 (OR, 1.86; 95% CI, 1.22–2.85). Type-specific associations with SCC were observed for HPV 8 (OR, 1.80; 95% CI, 1.14–2.84), 17 (OR, 1.59; 95% CI, 1.02–2.49) and HPV 10 from genus-alpha (OR, 2.24; 95% CI, 1.04–4.85). None of the type-specific associations remained statistically significant after correction for multiple comparisons. When DNA-positive SCC cases were compared with controls, strong serologic associations were observed for HPVs 5 (OR, 3.48; 95% CI, 1.27–9.59), 17 (OR, 3.36; 95% CI, 1.29–8.72), and 24 (OR, 3.79; 95% CI, 1.24–11.5). Conclusion: Genus-beta HPV infections were associated with SCC in our study population. Impact: Identifying the role of cutaneous HPV infection in SCC may lead to improved characterization of high-risk individuals and the development of novel prevention strategies. Cancer Epidemiol Biomarkers Prev; 21(8); 1303–13. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 3
    In: Journal of Investigative Dermatology, Elsevier BV, Vol. 133, No. 6 ( 2013-06), p. 1512-1520
    Type of Medium: Online Resource
    ISSN: 0022-202X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
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  • 4
    In: International Journal of Cancer, Wiley, Vol. 134, No. 9 ( 2014-05), p. 2231-2244
    Abstract: What's new Some HPVs contribute to cervical cancer, but other types, called genus beta HPVs, commonly infect the skin and are associated with squamous cell carcinoma. In this study, the authors investigated the association between genus‐beta HPV DNA found in plucked eyebrow hairs and the presence of SCC, as well as the presence of genus‐beta HPV DNA in the tumor tissue. They found that the viruses were found in eyebrow hairs more often in those with cancer than those without, suggesting that the virus plays a role in cancer development, and could make a good therapeutic target.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2014
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  • 5
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 21, No. 1 ( 2012-01-01), p. 74-81
    Abstract: Background: Merkel cell polyomavirus (MCV) DNA has been reported in 0% to 25% of squamous cell carcinomas (SCC) occurring in immunocompetent individuals. We conducted the first serologic case–control study of MCV and SCC. Methods: Patients with histologically confirmed cutaneous SCC (n = 173) were recruited from a university dermatology clinic. Controls were individuals who screened negative for and had no history of skin or other cancers (n = 300). Levels of antibodies against capsid antigens for MCV and another polyomavirus, JC virus (JCV), were determined by fluorescent bead-based multiplex serology. Fresh-frozen tumor tissues were obtained from 145 SCC cases and tested for MCV DNA by multiplexed PCR. Associations between MCV seroreactivity and SCC were estimated by ORs and 95% CIs calculated using logistic regression with adjustment for age and sex. Results: MCV DNA was detected in SCC tumor tissues from 55 (38%) of 145 cases. A statistically significant association was observed between MCV seropositivity and MCV DNA-positive SCC (OR = 2.49, 95% CI = 1.03–6.04), with an almost four-fold association observed when comparing those with MCV antibodies in the fourth versus first quartiles (OR = 3.93, 95% CI = 1.43–10.76, Ptrend = 0.01). No significant associations were observed between MCV seropositivity and MCV DNA-negative SCC (OR = 1.38, 95% CI = 0.76–2.48) or between JCV seropositivity and MCV DNA-positive or DNA-negative SCC. Conclusion: Past exposure to MCV may be a risk factor for SCC. Impact: Understanding the role of viral infections in the development of nonmelanoma skin cancer could lead to novel prevention strategies. Cancer Epidemiol Biomarkers Prev; 21(1); 74–81. ©2011 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4835-4835
    Abstract: Objective: Cutaneous human papillomavirus (HPV) antibodies and/or DNA in eyebrow hairs have been associated with cutaneous squamous cell carcinoma (SCC) in several case-control studies, including one from New Hampshire and ours from Florida. In the New Hampshire study, a single nucleotide polyomorphism (SNP) in the EVER2 gene (rs72080422) was associated with both SCC and cutaneous HPV seropositivity among controls (Patel et al Int J Cancer, 2008). Additional genetic variants in the EVER1/2 region of chromosome 17q25 have since been identified and shown to be associated with cervical cancer susceptibility (Castro et al Int J Cancer, 2011). We investigated the identical EVER1/2 variants in association with multiple markers of cutaneous HPV infection, including HPV seropositivity, and HPV DNA in eyebrow hairs and SCC tumor tissues. Methods: Patients with histologically-confirmed cutaneous SCC (n=142) were recruited from a university dermatology clinic in Tampa, FL. Controls were patients undergoing skin cancer screening exams who screened negative for skin cancer and reported no history of any type of cancer (n=265). Levels of antibodies against capsid antigens for 15 cutaneous HPV types in genus beta were determined by fluorescent bead-based multiplex serology. DNA for 25 beta-HPV types was measured in eyebrow hairs from cases and controls, and in fresh-frozen tumor tissues from 119 SCC cases using multiplex PCR. Twenty-one SNPs in in the EVER1/2 region of chromosome 17q25 were measured from eyebrow hair DNA, including rs7208422. Associations between EVER1/2 SNPs and SCC, and between EVER1/2 SNPs and HPV serostatus or DNA status, were estimated by odds ratios (OR) and 95% confidence intervals (CI) calculated using logistic regression with adjustment for age and sex. Results: None of the 21 SNPs in the EVER1/2 region were associated with SCC, including rs7208422 in EVER2, for which the TT genotype was observed in 23% of cases and 22% of controls (vs. AA: OR=0.99, 95% CI=0.52-1.90). Seropositivity for any beta-HPV type was not associated with any of the EVER1/2 SNPs among the cases or the controls, nor with seropositivity for HPV types 5 and/or 8 specifically. Beta-HPV DNA in eyebrow hairs was associated with two SNPs among the controls only (rs2290907, AG vs. AA: OR= 2.96, 95% CI=1.37-6.40; rs16970829, AG vs. AA: OR=12.8, 95% CI=1.71-95.90). Among the cases, beta-HPV DNA in tumor tissue was associated with rs7217374 (AG vs AG: OR=3.65, 95% CI=1.42-9.36; AA vs GG: OR=2.02, 95% CI=0.71-5.79), but not with any of the other 20 SNPs. Conclusion: In this small case-control study, genetic variation in the EVER1/2 region was not associated with SCC, and none of the 21 SNPs measured were consistently associated with different biomarkers of beta-HPV infection among cases or controls. Citation Format: Dana E. Rollison, Michelle R. Iannacone, Jane L. Messina, Neil A. Fenske, Basil S. Cherpelis, Vernon K. Sondak, Richard G. Roetzheim, Tarik Gheit, Massimo Tommasino, Markus Schmitt, Michael Pawlita. Genetic variation in EVER1/EVER2 and beta human papillomavirus infection in cutaneous squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4835. doi:10.1158/1538-7445.AM2013-4835
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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