Cutaneous ß HPVs, Sun Exposure, and Risk of Squamous and Basal Cell Skin Cancers in Australia.

BACKGROUND: Sun exposure causes cutaneous squamous (SCC) and basal cell (BCC) carcinomas. Human papillomavirus (HPV) infection might cause SCC. METHODS: We examined associations of ß and γ HPV infection in skin-swab DNA and serum antibodies with skin cancer risk, and modification of the carcinogenic effects of sun exposure by them, in case-control studies of 385 SCC cases, 832 BCC cases, and 1,100 controls nested in an Australian prospective cohort study (enrolled 2006-2009). RESULTS: Presence of ß-1 and ß-3 HPV DNA appeared to increase risks for SCC and BCC by 30% to 40% (P adjusted <0.01). BCC was also associated with genus ß DNA, OR = 1.48; 95% confidence interval (CI), 1.10 to 2.00 (P adjusted <0.01). Associations were strengthened with each additional positive ß HPV DNA type: SCC (OR = 1.07; 95% CI, 1.02-1.12) and BCC (OR = 1.06; 95% CI, 1.03-1.10), Ptrend<0.01. Positivity to genus ß or γ in serology, and genus γ in DNA, was not associated with either cancer. There was little evidence that any ß HPV type was more strongly associated than others with either cancer. A weaker association of sun exposure with SCC and BCC in the presence of ß-3 HPVs than in their absence suggests that ß-3 HPVs modify sun exposure's effect. CONCLUSIONS: Our substantive findings are at the level of genus ß HPV. Like SCC, BCC risk may increase with increasing numbers of ß HPV types on skin. IMPACT: The consistency in our findings that HPV infection may moderate the effects of sun exposure, the main environmental cause of SCC and BCC, merits further investigation.

High Ambient Solar UV Correlates with Greater Beta HPV Seropositivity in New South Wales, Australia.

BACKGROUND: Human papillomavirus (HPV) infection is highly prevalent worldwide and may have a role, with sun exposure, in causing cutaneous squamous cell carcinoma. Little is known about the relationship of UV exposure and seroprevalence of cutaneous HPVs in the general population. METHODS: Using multiplex serology, we estimated the seroprevalence of 23 beta and 7 gamma HPVs and 7 other antigens (mu HPV1, HPV63, nu HPV41, alpha HPV16; polyomaviruses HPyV7 and MCV; p53) in a population-based sample of 1,161 Australian 45 and Up Study participants with valid data from blood specimens collected from 2010 to 2012. We calculated prevalence ratios (PR) for the association of each antigen with residential ambient solar UV and other UV-related variables. RESULTS: Seropositivity for at least one beta or gamma HPV was high at 88% (beta HPVs 74%, gamma HPVs 70%), and less in women than men [e.g., PR beta-2 HPV38 = 0.70; 95% confidence interval (CI), 0.56-0.87; any gamma = 0.90; 95% CI, 0.84-0.97]. A high ambient UV level in the 10 years before study enrollment was associated with elevated seroprevalence for genus beta (PRtertile3vs1 any beta = 1.17; 95% CI, 1.07-1.28), and beta-1 to beta-3 species, but not for gamma HPVs. Other UV-related measures had less or no evidence of an association. CONCLUSIONS: Seroprevalence of cutaneous beta HPVs is higher with higher ambient UV exposure in the past 10 years. IMPACT: The observed association between ambient UV in the past 10 years and cutaneous HPVs supports further study of the possible joint role of solar UV and HPV in causing skin cancer.

Preanalytical Stability of Antibodies to Pathogenic Antigens.

Background: Serologic testing for antibodies against epitopes from pathogens is a valuable tool for investigating the relationship between infection and disease. This study comprehensively evaluates the impact of preanalytic variation on antibody seropositivities to a selected set of antigens arising from delays in processing of blood samples, preprocessing storage temperature, and vacutainer type.Methods: We assessed peripheral blood collected from 29 volunteers in four different Vacutainer types [ethylenediaminoetetraacetic acid (EDTA), acid-citrate-dextrose (ACD), lithium heparin (LH), serum separator tubes (SST)], and stored at 4°C or room temperature for 0, 1, 2, 3, 4, 5, and 6 days before processing. Multiplex serology was used to determine antibody reactivity against 35 antigens derived from human papillomaviruses, human polyomaviruses, Epstein-Barr virus, and Helicobacter pylori Cohen's κ statistic was used to measure agreement on seropositivity status between samples exposed to standard and nonstandard clinical practice conditions.Results: For samples processed without delay, κ was not associated with storage-temperature (P value range 0.23 to 0.95) or vacutainer type (P value range, 0.35-0.89). Kappa did not significantly decline with increasing delays in processing for any vacutainer-type storage temperature combination (P slope range, 0.06-1.00).Conclusions: Antibodies to epitopes from various pathogenic infectious agents can be measured reliably from samples stored in SST, EDTA, ACD, or LH vacutainers at either room temperature or 4°C for up to 6 days before processing.Impact: Serologic testing is robust to several preanalytic options. These findings are particularly important for epidemiologic studies recruiting participants from remote settings where sample exposure to preanalytic conditions can vary considerably. Cancer Epidemiol Biomarkers Prev; 26(8); 1337-44. ©2017 AACR.

Early Life UV and Risk of Basal and Squamous Cell Carcinoma in New South Wales, Australia.

Sun exposure is the main cause of squamous (SCC) and basal cell carcinoma (BCC) although pattern and amount differ by cancer type, and sun sensitivity is the major host risk factor. Our study investigated risk factors and residential ambient UV in a population-based sample of Australian 45 and Up Study participants: 916 BCC cases, 433 SCC cases, 1224 controls. Unconditional logistic regression models adjusting for key covariates demonstrated 60% increased BCC risk and two-fold increased SCC risk with sun sensitivity, and three- and four-fold increased risk, respectively, with solar keratoses. BCC but not SCC risk increased with higher early-life residential UV in all participants (odds ratio (OR) = 1.54; 95% CI 1.22-1.96 for intermediate; OR = 1.31; 95% CI 1.03-1.68 for high UV at birthplace) and similarly in Australian-born participants (P-values < 0.05). Risk of SCC but not BCC increased with long-term cumulative sun exposure assessed by self-reported outdoor work (OR 1.74, 95% CI 1.21-2.49). In conclusion, sun sensitivity is important for both cancers, early-life UV but not cumulative UV appears to increase BCC risk, the former an apparently novel finding, and SCC risk appears only to be related to long-term cumulative sun exposure.

Assays for Qualification and Quality Stratification of Clinical Biospecimens Used in Research: A Technical Report from the ISBER Biospecimen Science Working Group.

This technical report presents quality control (QC) assays that can be performed in order to qualify clinical biospecimens that have been biobanked for use in research. Some QC assays are specific to a disease area. Some QC assays are specific to a particular downstream analytical platform. When such a qualification is not possible, QC assays are presented that can be performed to stratify clinical biospecimens according to their biomolecular quality.