Dataset Information

Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer.

ABSTRACT:

Purpose

Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.

Methods

We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.

Results

HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.

Conclusion

HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.

SUBMITTER: Kreimer AR

PROVIDER: S-EPMC3709056 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer.

Kreimer Aimée R AR Johansson Mattias M Waterboer Tim T Kaaks Rudolf R Chang-Claude Jenny J Drogen Dagmar D Tjønneland Anne A Overvad Kim K Quirós J Ramón JR González Carlos A CA Sánchez Maria José MJ Larrañaga Nerea N Navarro Carmen C Barricarte Aurelio A Travis Ruth C RC Khaw Kay-Tee KT Wareham Nick N Trichopoulou Antonia A Lagiou Pagona P Trichopoulos Dimitrios D Peeters Petra H M PH Panico Salvatore S Masala Giovanna G Grioni Sara S Tumino Rosario R Vineis Paolo P Bueno-de-Mesquita H Bas HB Laurell Göran G Hallmans Göran G Manjer Jonas J Ekström Johanna J Skeie Guri G Lund Eiliv E Weiderpass Elisabete E Ferrari Pietro P Byrnes Graham G Romieu Isabelle I Riboli Elio E Hildesheim Allan A Boeing Heiner H Pawlita Michael M Brennan Paul P

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20130617 21

<h4>Purpose</h4>Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.<h4>Methods</h4>We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophage ...[more]

PMID: 23775966

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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.

Project description: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.

Dataset Information

Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer.

Purpose

Methods

Results

Conclusion

Publications

Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer.

Similar Datasets

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