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Cutaneous human papillomavirus infection, the EVER2 gene and incidence of squamous cell carcinoma: a case-control study.

ABSTRACT: The first evidence of an association between HPV and non-melanoma skin cancer comes from patients with epidermodysplasia verruciformis (EV). EV is a rare heritable disease characterized by cutaneous warts that display not only a high rate of progression to squamous cell carcinoma on sun-exposed sites, but also a strong predisposition to infection by beta-HPVs, for which HPV 5 and 8 predominate. Two EV genes (EVER1 and EVER2) have been identified, and we tested the hypothesis that variation in the EVER2 gene (rs7208422) is related to seropositivity to HPV (of the genus beta types) and risk of squamous cell carcinoma in a population-based case-control study of SCC (n = 239 cases and 432 controls). Among controls, variant genotype was associated with beta-HPV seropositvity (OR = 2.3, 95%CI = 1.2-4.3), specifically HPV5 or 8 seropositivity (OR = 2.4, 95%CI = 1.1-5.1) and seropositivity for multiple beta-HPV types (OR = 2.7, 95%CI = 1.1-6.6). Furthermore, variant genotype was also related to SCC risk [adjusted OR for homozygous variant versus homozygous wild type for the EVER2 polymorphism 1.7, 95% CI 1.1-2.7]. These data provide evidence for a role of genetic variation in the EVER2 gene in beta-HPV infection and risk of SCC, shedding light on the link between HPVs and skin cancers.

SUBMITTER: Patel AS

PROVIDER: S-EPMC2705140 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Cutaneous human papillomavirus infection, the EVER2 gene and incidence of squamous cell carcinoma: a case-control study.

Patel Anita S AS Karagas Margaret R MR Pawlita Michael M Waterboer Tim T Nelson Heather H HH

International journal of cancer 20080501 10

The first evidence of an association between HPV and non-melanoma skin cancer comes from patients with epidermodysplasia verruciformis (EV). EV is a rare heritable disease characterized by cutaneous warts that display not only a high rate of progression to squamous cell carcinoma on sun-exposed sites, but also a strong predisposition to infection by beta-HPVs, for which HPV 5 and 8 predominate. Two EV genes (EVER1 and EVER2) have been identified, and we tested the hypothesis that variation in th ...[more]

PMID: 18224692

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Project description:ImportanceCutaneous squamous cell carcinoma (cSCC) is the most common skin cancer with metastatic potential, but epidemiologic data are poor. Changes to the National Cancer Registration and Analysis Service (NCRAS) in England have allowed more accurate data analysis of primary and metastatic cSCC since 2013.ObjectiveTo assess the national incidence of cSCC and metastatic cSCC (mcSCC) in England from 2013 through 2015.Design, setting, and participantsThis national population-based study identified a cohort of patients with cSCC and mcSCC in England from January 1, 2013, through December 31, 2015. Patients were identified using diagnostic codes derived from pathology reports in the NCRAS. Data were analyzed from March 1, 2017, through March 1, 2018.Main outcomes and measuresIncidence rates across sex and risk factors for cSCC were derived from the NCRAS data. Risk of occurrence of mcSCC among the population with cSCC was assessed with Cox proportional hazards regression analysis to determine indicators of mcSCC.ResultsAmong the 76 977 patients with first primary cSCC in 2013 through 2015 (62.7% male; median age, 80 years [interquartile range, 72-86 years]), the age-standardized rates for the first registered cSCC in England from 2013 through 2015 were 77.3 per 100 000 person-years (PY) (95% CI, 76.6-78.0) in male patients and 34.1 per 100 000 PY (95% CI, 33.7-34.5) in female patients. Increased primary cSCC tumor count was observed in older, white male patients in lower deprivation quintiles. After a maximum follow-up of 36 months, cumulative incidence of mcSCC developed in 1.1% of women and 2.4% of men with a primary cSCC. Significant increases in the risk of metastasis with adjusted hazard rates of approximately 2.00 were observed in patients who were aged 80 to 89 years (hazard ratio [HR], 1.23; 95% CI, 1.07-1.43), 90 years or older (HR, 1.35; 95% CI, 1.09-1.66), male (HR, 1.79; 95% CI, 1.52-2.10), immunosuppressed (HR, 1.99; 95% CI, 1.64-2.42), and in higher deprivation quintiles (HR for highest quintile, 1.64; 95% CI, 1.35-2.00). Primary cSCC located on the ear (HR, 1.70; 95% CI, 1.42-2.03) and lip (HR, 1.85; 95% CI, 1.29-2.63) were at highest risk of metastasis.Conclusions and relevanceThis study presents the first national study of the incidence of mcSCC. With limited health care resources and an aging population, accurate epidemiologic data are essential for informing future health care planning, identifying high-risk patients, and evaluating skin cancer prevention policies.

Project description:Cutaneous squamous cell carcinoma (cSCC) has metastatic potential, but the prognostic value of current staging systems in nonselected patients is uncertain.To assess the effect of risk factors for metastasis and to evaluate validity and usefulness of 4 staging systems for cSCC using population-based data.This was a nationwide, population-based, nested case-control study. The Cancer Registry of Norway, which receives compulsory data on all cancers in the Norwegian population of approximately 5.2 million inhabitants. All patients diagnosed as having a primary invasive cSCC in the period 2000 to 2004 (n = 6721) were identified. Of these, 112 patients were diagnosed with metastasis within 5 years. As control patients, 112 patients with cSCC without metastases, matched for sex and age at diagnosis, were identified by random. Clinical data and biopsy specimens of primary cSCC were collected for all 224 patients. The biopsies were reexamined histologically by an experienced pathologist using well-established criteria for cSCC, yielding 103 patients with metastasis (cases) and 81 cSCC without metastasis (controls).The ability of 4 cSCC staging systems (ie, the American Joint Committee on Cancer, 7th edition [AJCC 7] staging system, the staging system used by Breuninger et al, the Brigham and Women's Hospital [BWH] staging system, and the AJCC, 8th edition [AJCC 8] staging systems) to identify patients who developed metastasis with 5 years of follow-up. External validation was performed by logistic regression, discrimination (sensitivity, specificity, proportion correctly classified, concordance index), and calibration (R2, Hosmer-Lemeshow test, plots) statistics.Of 6721 patients; 3674 (54.7%) were men and 3047 (45.3%) were women, with a mean age at diagnosis of 78 years. Of the 103 patients with cSCC diagnosed with metastasis within 5 years, 60 [58.3%] were men, and mean [SD] age 72.7 [13.5] years. Of the 81 patients with cSCC without metastasis, 51 [63.0%] were men, and mean [SD] age 74.6 [11.7] 15 years. The staging systems distinguished poorly to moderately between patients who developed metastasis and those who did not. The ability to cluster patients with similar outcomes within the same staging category was low, particularly when using the AJCC 7 system. Using the AJCC 7 system, the risk of metastasis for T2 patients was 3-fold, compared with T1 patients (OR, 2.96; 95% CI, 1.43-6.15). In the system used by Breuninger et al, high-risk categories for diameter and tumor thickness and the BWH system's T2b category collected relatively homogeneous groups. In the systems used by Breuninger et al and Brigham-Women's Hospital, risk of metastasis was significantly elevated with increasing stage or risk category. Using the system by Breuninger et al, the risk of metastasis was less than 3-fold for tumors in the high-risk category of the combined variable (OR, 2.72; 95% CI, 1.29-5.74). The BWH system gave ORs for metastasis at 4.6 (95% CI, 2.23-9.49) and 21.31 (95% CI, 6.07-74.88) for the T2a and T2b categories, respectively.Using population-based data, 4 current staging systems for cSCC were unsatisfactory in identifying nonselected cSCC patients at high risk for metastasis. The system used by Breuninger gave the best results.

Dataset Information

Cutaneous human papillomavirus infection, the EVER2 gene and incidence of squamous cell carcinoma: a case-control study.

Publications

Cutaneous human papillomavirus infection, the EVER2 gene and incidence of squamous cell carcinoma: a case-control study.

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