title: Measures of cutaneous human papillomavirus infection in normal tissues as biomarkers of HPV in corresponding nonmelanoma skin cancers.
abstract: Cutaneous human papillomavirus (HPV) may be associated with the development of nonmelanoma skin cancer (NMSC), as suggested by reports of HPV DNA in NMSC tumors. HPV has also been investigated as an NMSC risk factor in epidemiologic studies, although findings vary across studies that used different biomarkers of HPV infection in normal tissues. To identify appropriate biomarkers for use in future epidemiologic studies, we conducted a sampling validation study. NMSC tumor tissue was obtained from 20 patients with pathology-confirmed basal or squamous cell carcinoma of the skin, in addition to several normal tissues, including eyebrow hairs, normal skin swabs obtained using multiple techniques, normal skin punch and shave biopsies, and serum for antibody measurement. Presence of cutaneous HPV DNA in tissues was measured with multiplex PCR using HPV type-specific primers and array primer extension (APEX) for HPV typing. Antibody detection was based on glutathione-S-transferase capture ELISA in combination with fluorescent bead technology. Using HPV DNA in tumor tissues as a gold standard, sensitivity and specificity were calculated for each measure of HPV infection in normal tissues. beta-Papillomavirus DNA was observed in tumor tissues in 60% of patients. The normal skin punch biopsy demonstrated optimal sensitivity (75%) and specificity (75%). Biomarkers obtained using less-invasive techniques demonstrated poor specificity when considered individually, although specificity improved when biomarkers were combined. Based on the current case series, the combinations of antibodies+eyebrow hairs or antibodies+eyebrow hairs+Dacron swabs are the optimal, minimally invasive markers of cutaneous HPV infection for use in epidemiologic studies.
authors: Division of Cancer Prevention and Control, Moffitt Cancer Center, Tampa, FL, USA. dana.rollison@moffitt.org
authors: Dana E
authors: DE
authors: Rollison
authors: Michael
authors: M
authors: Pawlita
authors: Anna R
authors: AR
authors: Giuliano
authors: Michelle R
authors: MR
authors: Iannacone
authors: Vernon K
authors: VK
authors: Sondak
authors: Jane L
authors: JL
authors: Messina
authors: C Wayne
authors: CW
authors: Cruse
authors: Neil Alan
authors: NA
authors: Fenske
authors: Lewis Frank
authors: LF
authors: Glass
authors: Matthew
authors: M
authors: Kienstra
authors: Kristina M
authors: KM
authors: Michael
authors: Tim
authors: T
authors: Waterboer
authors: Tarik
authors: T
authors: Gheit
authors: Massimo
authors: M
authors: Tommasino
mesh_terms: D052686:Betapapillomavirus / Q000302:isolation & purification; D015415:Biomarkers / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000378:metabolism / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D030361:Papillomavirus Infections / Q000378:metabolism / Q000821:virology*; D012307:Risk Factors; D017193:Skin Diseases, Viral / Q000378:metabolism / Q000821:virology*; D012878:Skin Neoplasms / Q000378:metabolism / Q000821:virology*
chemical_list: D015415:Biomarkers