Associations of oral α-, β-, and γ-human papillomavirus types with risk of incident head and neck cancer

Ilir Agalliu, Susan Gapstur, Zigui Chen, Tao Wang, Rebecca L. Anderson, Lauren Teras, Aimee R. Kreimer, Richard B. Hayes, Neal D. Freedman, Robert D. Burk

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Abstract

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 α-, β-, and γ-HPV types, but their association with risk of HNSCC is unknown. OBJECTIVE To prospectively examine associations between α-, β-, and γ-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 α-, β-, and γ-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 β- and γ-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 β1-HPV-5 and β2-HPV-38 types, as well as γ-11 and γ-12 species, had ORs for HNSCC that ranged from 2.64 to 5.45 (P < .01 for all comparisons). Detection of β1-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 γ11- and γ12-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 γ11- and γ12-HPV species and β1-HPV-5 type suggest a broader role for HPVs in HNSCC etiology.

Original languageEnglish (US)
Pages (from-to)599-606
Number of pages8
JournalJAMA oncology
Volume2
Issue number5
DOIs
StatePublished - May 1 2016

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Head and Neck Neoplasms
Odds Ratio
Mouth
Human papillomavirus 16
Mouthwashes
Human papillomavirus 11
Logistic Models
Prospective Studies
Oropharyngeal Neoplasms
Carcinoma, squamous cell of head and neck
Mouth Neoplasms
Incidence
Larynx
DNA Sequence Analysis
Early Detection of Cancer
Alcohol Drinking
Ovarian Neoplasms
Case-Control Studies
Colorectal Neoplasms
Lung Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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Associations of oral α-, β-, and γ-human papillomavirus types with risk of incident head and neck cancer. / Agalliu, Ilir; Gapstur, Susan; Chen, Zigui; Wang, Tao; Anderson, Rebecca L.; Teras, Lauren; Kreimer, Aimee R.; Hayes, Richard B.; Freedman, Neal D.; Burk, Robert D.

In: JAMA oncology, Vol. 2, No. 5, 01.05.2016, p. 599-606.

Research output: Contribution to journalArticle

Agalliu, Ilir ; Gapstur, Susan ; Chen, Zigui ; Wang, Tao ; Anderson, Rebecca L. ; Teras, Lauren ; Kreimer, Aimee R. ; Hayes, Richard B. ; Freedman, Neal D. ; Burk, Robert D. / Associations of oral α-, β-, and γ-human papillomavirus types with risk of incident head and neck cancer. In: JAMA oncology. 2016 ; Vol. 2, No. 5. pp. 599-606.
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abstract = "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 α-, β-, and γ-HPV types, but their association with risk of HNSCC is unknown. OBJECTIVE To prospectively examine associations between α-, β-, and γ-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 α-, β-, and γ-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 β- and γ-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 β1-HPV-5 and β2-HPV-38 types, as well as γ-11 and γ-12 species, had ORs for HNSCC that ranged from 2.64 to 5.45 (P < .01 for all comparisons). Detection of β1-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 γ11- and γ12-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 γ11- and γ12-HPV species and β1-HPV-5 type suggest a broader role for HPVs in HNSCC etiology.",
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TY - JOUR

T1 - Associations of oral α-, β-, and γ-human papillomavirus types with risk of incident head and neck cancer

AU - Agalliu, Ilir

AU - Gapstur, Susan

AU - Chen, Zigui

AU - Wang, Tao

AU - Anderson, Rebecca L.

AU - Teras, Lauren

AU - Kreimer, Aimee R.

AU - Hayes, Richard B.

AU - Freedman, Neal D.

AU - Burk, Robert D.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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 α-, β-, and γ-HPV types, but their association with risk of HNSCC is unknown. OBJECTIVE To prospectively examine associations between α-, β-, and γ-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 α-, β-, and γ-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 β- and γ-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 β1-HPV-5 and β2-HPV-38 types, as well as γ-11 and γ-12 species, had ORs for HNSCC that ranged from 2.64 to 5.45 (P < .01 for all comparisons). Detection of β1-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 γ11- and γ12-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 γ11- and γ12-HPV species and β1-HPV-5 type suggest a broader role for HPVs in HNSCC etiology.

AB - 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 α-, β-, and γ-HPV types, but their association with risk of HNSCC is unknown. OBJECTIVE To prospectively examine associations between α-, β-, and γ-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 α-, β-, and γ-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 β- and γ-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 β1-HPV-5 and β2-HPV-38 types, as well as γ-11 and γ-12 species, had ORs for HNSCC that ranged from 2.64 to 5.45 (P < .01 for all comparisons). Detection of β1-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 γ11- and γ12-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 γ11- and γ12-HPV species and β1-HPV-5 type suggest a broader role for HPVs in HNSCC etiology.

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