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A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer.

ABSTRACT: Detection of human papillomavirus (HPV) in head and neck cancer has therapeutic implications. In situ hybridization and immunohistochemistry for p16 are used by surgical pathologists. We compared the sensitivity and specificity of three popular commercial tests for HPV detection in head and neck squamous cell carcinomas with a 'gold standard' HPV PCR assay. A total of 110 prospectively collected, formalin-fixed tumor specimens were compiled onto tissue microarrays and tested for HPV DNA by in situ hybridization with two probe sets, a biotinylated probe for high-risk (HR) HPV types 16/18 (Dako, CA, USA) and a probe cocktail for 16/18, plus 10 additional HR types (Ventana, AZ, USA). The p16(INK4) expression was also assessed using a Pharmingen immunohistochemistry antibody (BD Biosciences, CA, USA). Tissue microarrays were stained and scored at expert laboratories. HPV DNA was detected by MY09/11-PCR, using Gold AmpliTaq and dot-blot hybridization on matched-fresh frozen specimens in a research laboratory. HPV 16 E6 and E7-RNA expression was also measured using RT-PCR. Test performance was assessed by a receiver operating characteristic analysis. HR-HPV DNA types 16, 18 and 35 were detected by MY-PCR in 28% of tumors, with the majority (97%) testing positive for type 16. Compared with MY-PCR, the sensitivity and specificity for HR-HPV DNA detection with Dako in situ hybridization was 21% (95% confidence interval (CI): 7-42) and 100% (95% CI: 93-100), respectively. Corresponding test results by Ventana in situ hybridization were 59% (95% CI: 39-78) and 58% (95% CI: 45-71), respectively. The p16 immunohistochemistry performed better overall than Dako (P=0.042) and Ventana (P=0.055), with a sensitivity of 52% (95% CI: 32-71) and specificity of 93% (95% CI: 84-98). Compared with a gold standard HPV-PCR assay, HPV detection by in situ hybridization was less accurate for head and neck squamous cell carcinoma on tissue microarrays than p16 immunohistochemistry. Further testing is warranted before these assays should be recommended for clinical HPV detection.

SUBMITTER: Schlecht NF

PROVIDER: S-EPMC3157570 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer.

Schlecht Nicolas F NF Brandwein-Gensler Margaret M Nuovo Gerard J GJ Li Maomi M Dunne Anne A Kawachi Nicole N Smith Richard V RV Burk Robert D RD Prystowsky Michael B MB

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20110513 10

Detection of human papillomavirus (HPV) in head and neck cancer has therapeutic implications. In situ hybridization and immunohistochemistry for p16 are used by surgical pathologists. We compared the sensitivity and specificity of three popular commercial tests for HPV detection in head and neck squamous cell carcinomas with a 'gold standard' HPV PCR assay. A total of 110 prospectively collected, formalin-fixed tumor specimens were compiled onto tissue microarrays and tested for HPV DNA by in si ...[more]

PMID: 21572401

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Project description:BackgroundAlthough the majority of human papillomavirus (HPV) infections are cleared by the immune system, a small percentage of them progress to develop HPV-driven cancers. Cervical cancer studies highlight that HPV persistence and cancer risk are associated with genetic factors, especially at the human leukocyte antigen (HLA) genes. This study was conducted to investigate such associations in head and neck cancer (HNC).MethodsIn all, 192 patients with HNC and 384 controls were genotyped with the Infinium Global Screening Array (Illumina, Inc). HLA variants were imputed with SNP2HLA, and an association analysis was performed by logistic regression.ResultsHPV-positive HNCs were significantly associated with single-nucleotide polymorphisms (SNPs) at DRB1_32660090 (P = 1.728 × 10-6 ) and DRB1_32660116 (P = 1.728 × 10-6 ) and with the amino acid variant DRB1_11_32660115 (P = 1.728 × 10-6 ). None of these associations were observed in the HPV-negative cohort, and this suggested their specificity to convey risk for HPV-associated HNCs. In general, associations observed for HPV-negative HNC were relatively weak, and variants in the HLA-DPA1 region were the strongest among them (P = 4.531 × 10-4 ). Several lead signals reported by previous HNC genome-wide association studies, including SNPs rs3135001 (P = .012), rs1049055 (P = .012), and rs34518860 (P = .029) and allele HLA-DQB1*06 (P = .009), were replicated in the current study. However, these associations were limited to the HPV-positive HNC group. Several cervical cancer-associated HLA variants, including SNPs rs9272143 (P = .002) and rs9271858 (P = .002) and alleles HLA-B-1501 (P = .009) and HLA-B-15 (P = .015), were also exclusively associated with HPV-positive HNC.ConclusionsHPV-positive HNC risk is associated with distinct HLA variants, and some of them are shared by both cervical cancer and HPV-positive HNC. Human papillomavirus (HPV)-positive head and neck cancer (HNC) risk is associated with distinct human leukocyte antigen variants, and some of them are shared by both cervical cancer and HPV-positive HNC.Lay summaryCervical cancer studies highlight that human papillomavirus (HPV)-driven cancer risk is linked with human leukocyte antigen (HLA) polymorphism. Hence, the current study was designed to investigate the HLA associations in HPV-positive and HPV-negative head and neck cancer (HNC) and compare these associations with cervical cancer. Several lead signals reported by previous HNC and cervical genome-wide association studies were replicated in the current study. However, these associations were limited to the HPV-positive HNC group, and this suggests that HPV-positive HNC risk is associated with distinct HLA variants, and some of them are shared by both cervical cancer and HPV-positive HNC.

Project description:Importance:Prospective studies are needed to examine the temporal relationship between oral human papillomavirus (HPV) detection and risk of head and neck squamous cell carcinoma (HNSCC). Moreover, the oral cavity contains a wide spectrum of ?-, ?-, and ?-HPV types, but their association with risk of HNSCC is unknown. Objective:To prospectively examine associations between ?-, ?-, and ?-HPV detection in the oral cavity and incident HNSCC. Design:A nested case-control study was carried out among 96?650 participants, cancer free at baseline, with available mouthwash samples in 2 prospective cohort studies: (1) the American Cancer Society Cancer Prevention Study II Nutrition Cohort and (2) the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Incident cases of HNSCC (n?=?132) were identified during an average 3.9 years of follow-up in both cohorts. Three controls per case (n?=?396) were selected through incidence density sampling and matched on age, sex, race/ethnicity, and time since mouthwash collection. Methods:Through a next-generation sequencing assay, DNA from ?-, ?-, and ?-HPV types were detected. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs, adjusting for smoking history, alcohol consumption, and detection of HPV-16 for ?- and ?-HPVs. Main Outcomes and Measures:Incident HNSCC, which includes cancers of the oropharynx, oral cavity, and larynx. Results:A total of 132 participants developed HNSCC during the follow-up period (103 men and 29 women; average age at baseline, 66.5 years). Oral HPV-16 detection was associated with incident HNSCC (OR, 7.1; 95% CI, 2.2-22.6), with positive association for oropharyngeal SCC (OR, 22.4; 95% CI, 1.8-276.7), but not for oral cavity (OR, 4.5; 95% CI, 0.6-34.7) or laryngeal SCCs (OR, 0.11; 95% CI, 0.01-834.80). Detection of ?1-HPV-5 and ?2-HPV-38 types, as well as ?-11 and ?-12 species, had ORs for HNSCC that ranged from 2.64 to 5.45 (P?<?.01 for all comparisons). Detection of ?1-HPV-5 type was associated with oropharyngeal (OR, 7.42; 95% CI, 0.98-56.82; P?=?.054), oral cavity (OR, 5.34; 95% CI, 1.51-18.80; P?=?.01), and laryngeal SCCs (OR, 2.71; 95% CI, 1.00-7.43; P?=?.05), whereas ?11- and ?12-HPV species were associated with both oral cavity (OR, 7.47; 95% CI, 1.21-46.17; P?=?.03; and OR, 6.71; 95% CI, 1.47-30.75; P?=?.01, respectively) and laryngeal SCCs (OR, 7.49; 95% CI, 1.10-51.04; P?=?.04 and OR, 5.31; 95% CI, 1.13-24.95; P?=?.03, respectively). Conclusions and Relevance:This study demonstrates that HPV-16 detection precedes the incidence of oropharyngeal SCC. Associations of other HPVs, including ?11- and ?12-HPV species and ?1-HPV-5 type suggest a broader role for HPVs in HNSCC etiology.

Dataset Information

A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer.

Publications

A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer.

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