Human papillomavirus infections and upper aero-digestive tract cancers

the ARCAGE study

Devasena Anantharaman, Tarik Gheit, Tim Waterboer, Behnoush Abedi-Ardekani, Christine Carreira, Sandrine McKay-Chopin, Valerie Gaborieau, Manuela Marron, Pagona Lagiou, Wolfgang Ahrens, Ivana Holcátová, Franco Merletti, Kristina Kjaerheim, Renato Talamini, Lorenzo Simonato, Xavier Castellsague, Tatiana MacFarlane, Anne-Marie Biggs, Nalin Thakker, Ariana Znaor & 7 others Peter Thomson, Cristina Canova, David I Conway, Claire M Healy, Massimo Tommasino, Michael Pawlita, Paul Brennan

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Human papillomavirus (HPV) is causally implicated in a subset of cancers of the upper aero-digestive tract (UADT).

METHODS: Associations between type-specific HPV antibodies were examined among 1496 UADT cancer case subjects and 1425 control subjects by estimating odds ratios (ORs) in logistic regression analyses adjusted for potential confounders. The agreement between serology and tumor markers of HPV infection, including presence of HPV DNA and p16 expression, were examined in a subset of tumors.

RESULTS: HPV16 L1 seropositivity was associated with increased risk of oral cavity and oropharyngeal cancer (OR = 1.94, 95% confidence interval [CI] = 1.03 to 3.65; OR = 8.60, 95% CI = 5.21 to 14.20, respectively). HPV16 E6 antibodies were present in 30.2% of oropharyngeal case subjects and only 0.8% of control subjects (OR = 132.0, 95% CI = 65.29 to 266.86). Combined seropositivity to HPV16 E6 and E7 was rare (n = 1 of 1425 control subjects). An agreement of 67% was observed between HPV16 E6 serology and the corresponding presence of an HPV-related cancer: four of six HPV DNA-positive/p16-overexpressing tumors were HPV16 E6 antibody positive. An HPV16 independent association was observed for HPV18 and oropharyngeal cancer (OR = 8.14, 95% CI = 2.21 to 29.99 for HPV18 E6 seropositivity) and HPV6 and laryngeal cancer (OR = 3.25, 95% CI = 1.46 to 7.24 for HPV6 E7 seropositivity).

CONCLUSIONS: These results confirm an important role for HPV16 infection in oropharyngeal cancer. HPV16 E6 antibodies are strongly associated with HPV16-related oropharyngeal cancers. Continuing efforts are needed to consider both HPV serology and p16 staining as biomarkers relevant to the etiology and natural history of HPV16-related oropharyngeal tumors. These results also support a marginal role for HPV18 in oropharyngeal cancer and HPV6 in laryngeal cancer.

Original languageEnglish
Pages (from-to)536-545
Number of pages10
JournalJournal of the National Cancer Institute
Volume105
Issue number8
DOIs
Publication statusPublished - 17 Apr 2013

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Papillomavirus Infections
Oropharyngeal Neoplasms
Gastrointestinal Tract
Odds Ratio
Confidence Intervals
Serology
Neoplasms
Laryngeal Neoplasms
Antibodies
Mouth Neoplasms
DNA
Tumor Biomarkers
Natural History
Mouth
Biomarkers
Logistic Models
Regression Analysis
Staining and Labeling
Infection

Keywords

  • Aged
  • Antibodies, Viral
  • Case-Control Studies
  • DNA, Viral
  • Female
  • Fluorescent Antibody Technique
  • Human papillomavirus 16
  • Humans
  • Laryngeal Neoplasms
  • Logistic Models
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Odds Ratio
  • Oncogene Proteins, Viral
  • Oropharyngeal Neoplasms
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections
  • Polymerase Chain Reaction
  • Repressor Proteins
  • Tumor Markers, Biological
  • Up-Regulation

Cite this

Anantharaman, D., Gheit, T., Waterboer, T., Abedi-Ardekani, B., Carreira, C., McKay-Chopin, S., ... Brennan, P. (2013). Human papillomavirus infections and upper aero-digestive tract cancers: the ARCAGE study. Journal of the National Cancer Institute, 105(8), 536-545. https://doi.org/10.1093/jnci/djt053

Human papillomavirus infections and upper aero-digestive tract cancers : the ARCAGE study. / Anantharaman, Devasena; Gheit, Tarik; Waterboer, Tim; Abedi-Ardekani, Behnoush; Carreira, Christine; McKay-Chopin, Sandrine; Gaborieau, Valerie; Marron, Manuela; Lagiou, Pagona; Ahrens, Wolfgang; Holcátová, Ivana; Merletti, Franco; Kjaerheim, Kristina; Talamini, Renato; Simonato, Lorenzo; Castellsague, Xavier; MacFarlane, Tatiana; Biggs, Anne-Marie; Thakker, Nalin; Znaor, Ariana; Thomson, Peter; Canova, Cristina; Conway, David I; Healy, Claire M; Tommasino, Massimo; Pawlita, Michael; Brennan, Paul.

In: Journal of the National Cancer Institute, Vol. 105, No. 8, 17.04.2013, p. 536-545.

Research output: Contribution to journalArticle

Anantharaman, D, Gheit, T, Waterboer, T, Abedi-Ardekani, B, Carreira, C, McKay-Chopin, S, Gaborieau, V, Marron, M, Lagiou, P, Ahrens, W, Holcátová, I, Merletti, F, Kjaerheim, K, Talamini, R, Simonato, L, Castellsague, X, MacFarlane, T, Biggs, A-M, Thakker, N, Znaor, A, Thomson, P, Canova, C, Conway, DI, Healy, CM, Tommasino, M, Pawlita, M & Brennan, P 2013, 'Human papillomavirus infections and upper aero-digestive tract cancers: the ARCAGE study', Journal of the National Cancer Institute, vol. 105, no. 8, pp. 536-545. https://doi.org/10.1093/jnci/djt053
Anantharaman D, Gheit T, Waterboer T, Abedi-Ardekani B, Carreira C, McKay-Chopin S et al. Human papillomavirus infections and upper aero-digestive tract cancers: the ARCAGE study. Journal of the National Cancer Institute. 2013 Apr 17;105(8):536-545. https://doi.org/10.1093/jnci/djt053
Anantharaman, Devasena ; Gheit, Tarik ; Waterboer, Tim ; Abedi-Ardekani, Behnoush ; Carreira, Christine ; McKay-Chopin, Sandrine ; Gaborieau, Valerie ; Marron, Manuela ; Lagiou, Pagona ; Ahrens, Wolfgang ; Holcátová, Ivana ; Merletti, Franco ; Kjaerheim, Kristina ; Talamini, Renato ; Simonato, Lorenzo ; Castellsague, Xavier ; MacFarlane, Tatiana ; Biggs, Anne-Marie ; Thakker, Nalin ; Znaor, Ariana ; Thomson, Peter ; Canova, Cristina ; Conway, David I ; Healy, Claire M ; Tommasino, Massimo ; Pawlita, Michael ; Brennan, Paul. / Human papillomavirus infections and upper aero-digestive tract cancers : the ARCAGE study. In: Journal of the National Cancer Institute. 2013 ; Vol. 105, No. 8. pp. 536-545.
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title = "Human papillomavirus infections and upper aero-digestive tract cancers: the ARCAGE study",
abstract = "BACKGROUND: Human papillomavirus (HPV) is causally implicated in a subset of cancers of the upper aero-digestive tract (UADT).METHODS: Associations between type-specific HPV antibodies were examined among 1496 UADT cancer case subjects and 1425 control subjects by estimating odds ratios (ORs) in logistic regression analyses adjusted for potential confounders. The agreement between serology and tumor markers of HPV infection, including presence of HPV DNA and p16 expression, were examined in a subset of tumors.RESULTS: HPV16 L1 seropositivity was associated with increased risk of oral cavity and oropharyngeal cancer (OR = 1.94, 95{\%} confidence interval [CI] = 1.03 to 3.65; OR = 8.60, 95{\%} CI = 5.21 to 14.20, respectively). HPV16 E6 antibodies were present in 30.2{\%} of oropharyngeal case subjects and only 0.8{\%} of control subjects (OR = 132.0, 95{\%} CI = 65.29 to 266.86). Combined seropositivity to HPV16 E6 and E7 was rare (n = 1 of 1425 control subjects). An agreement of 67{\%} was observed between HPV16 E6 serology and the corresponding presence of an HPV-related cancer: four of six HPV DNA-positive/p16-overexpressing tumors were HPV16 E6 antibody positive. An HPV16 independent association was observed for HPV18 and oropharyngeal cancer (OR = 8.14, 95{\%} CI = 2.21 to 29.99 for HPV18 E6 seropositivity) and HPV6 and laryngeal cancer (OR = 3.25, 95{\%} CI = 1.46 to 7.24 for HPV6 E7 seropositivity).CONCLUSIONS: These results confirm an important role for HPV16 infection in oropharyngeal cancer. HPV16 E6 antibodies are strongly associated with HPV16-related oropharyngeal cancers. Continuing efforts are needed to consider both HPV serology and p16 staining as biomarkers relevant to the etiology and natural history of HPV16-related oropharyngeal tumors. These results also support a marginal role for HPV18 in oropharyngeal cancer and HPV6 in laryngeal cancer.",
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TY - JOUR

T1 - Human papillomavirus infections and upper aero-digestive tract cancers

T2 - the ARCAGE study

AU - Anantharaman, Devasena

AU - Gheit, Tarik

AU - Waterboer, Tim

AU - Abedi-Ardekani, Behnoush

AU - Carreira, Christine

AU - McKay-Chopin, Sandrine

AU - Gaborieau, Valerie

AU - Marron, Manuela

AU - Lagiou, Pagona

AU - Ahrens, Wolfgang

AU - Holcátová, Ivana

AU - Merletti, Franco

AU - Kjaerheim, Kristina

AU - Talamini, Renato

AU - Simonato, Lorenzo

AU - Castellsague, Xavier

AU - MacFarlane, Tatiana

AU - Biggs, Anne-Marie

AU - Thakker, Nalin

AU - Znaor, Ariana

AU - Thomson, Peter

AU - Canova, Cristina

AU - Conway, David I

AU - Healy, Claire M

AU - Tommasino, Massimo

AU - Pawlita, Michael

AU - Brennan, Paul

PY - 2013/4/17

Y1 - 2013/4/17

N2 - BACKGROUND: Human papillomavirus (HPV) is causally implicated in a subset of cancers of the upper aero-digestive tract (UADT).METHODS: Associations between type-specific HPV antibodies were examined among 1496 UADT cancer case subjects and 1425 control subjects by estimating odds ratios (ORs) in logistic regression analyses adjusted for potential confounders. The agreement between serology and tumor markers of HPV infection, including presence of HPV DNA and p16 expression, were examined in a subset of tumors.RESULTS: HPV16 L1 seropositivity was associated with increased risk of oral cavity and oropharyngeal cancer (OR = 1.94, 95% confidence interval [CI] = 1.03 to 3.65; OR = 8.60, 95% CI = 5.21 to 14.20, respectively). HPV16 E6 antibodies were present in 30.2% of oropharyngeal case subjects and only 0.8% of control subjects (OR = 132.0, 95% CI = 65.29 to 266.86). Combined seropositivity to HPV16 E6 and E7 was rare (n = 1 of 1425 control subjects). An agreement of 67% was observed between HPV16 E6 serology and the corresponding presence of an HPV-related cancer: four of six HPV DNA-positive/p16-overexpressing tumors were HPV16 E6 antibody positive. An HPV16 independent association was observed for HPV18 and oropharyngeal cancer (OR = 8.14, 95% CI = 2.21 to 29.99 for HPV18 E6 seropositivity) and HPV6 and laryngeal cancer (OR = 3.25, 95% CI = 1.46 to 7.24 for HPV6 E7 seropositivity).CONCLUSIONS: These results confirm an important role for HPV16 infection in oropharyngeal cancer. HPV16 E6 antibodies are strongly associated with HPV16-related oropharyngeal cancers. Continuing efforts are needed to consider both HPV serology and p16 staining as biomarkers relevant to the etiology and natural history of HPV16-related oropharyngeal tumors. These results also support a marginal role for HPV18 in oropharyngeal cancer and HPV6 in laryngeal cancer.

AB - BACKGROUND: Human papillomavirus (HPV) is causally implicated in a subset of cancers of the upper aero-digestive tract (UADT).METHODS: Associations between type-specific HPV antibodies were examined among 1496 UADT cancer case subjects and 1425 control subjects by estimating odds ratios (ORs) in logistic regression analyses adjusted for potential confounders. The agreement between serology and tumor markers of HPV infection, including presence of HPV DNA and p16 expression, were examined in a subset of tumors.RESULTS: HPV16 L1 seropositivity was associated with increased risk of oral cavity and oropharyngeal cancer (OR = 1.94, 95% confidence interval [CI] = 1.03 to 3.65; OR = 8.60, 95% CI = 5.21 to 14.20, respectively). HPV16 E6 antibodies were present in 30.2% of oropharyngeal case subjects and only 0.8% of control subjects (OR = 132.0, 95% CI = 65.29 to 266.86). Combined seropositivity to HPV16 E6 and E7 was rare (n = 1 of 1425 control subjects). An agreement of 67% was observed between HPV16 E6 serology and the corresponding presence of an HPV-related cancer: four of six HPV DNA-positive/p16-overexpressing tumors were HPV16 E6 antibody positive. An HPV16 independent association was observed for HPV18 and oropharyngeal cancer (OR = 8.14, 95% CI = 2.21 to 29.99 for HPV18 E6 seropositivity) and HPV6 and laryngeal cancer (OR = 3.25, 95% CI = 1.46 to 7.24 for HPV6 E7 seropositivity).CONCLUSIONS: These results confirm an important role for HPV16 infection in oropharyngeal cancer. HPV16 E6 antibodies are strongly associated with HPV16-related oropharyngeal cancers. Continuing efforts are needed to consider both HPV serology and p16 staining as biomarkers relevant to the etiology and natural history of HPV16-related oropharyngeal tumors. These results also support a marginal role for HPV18 in oropharyngeal cancer and HPV6 in laryngeal cancer.

KW - Aged

KW - Antibodies, Viral

KW - Case-Control Studies

KW - DNA, Viral

KW - Female

KW - Fluorescent Antibody Technique

KW - Human papillomavirus 16

KW - Humans

KW - Laryngeal Neoplasms

KW - Logistic Models

KW - Male

KW - Middle Aged

KW - Neoplasm Staging

KW - Odds Ratio

KW - Oncogene Proteins, Viral

KW - Oropharyngeal Neoplasms

KW - Papillomavirus E7 Proteins

KW - Papillomavirus Infections

KW - Polymerase Chain Reaction

KW - Repressor Proteins

KW - Tumor Markers, Biological

KW - Up-Regulation

U2 - 10.1093/jnci/djt053

DO - 10.1093/jnci/djt053

M3 - Article

VL - 105

SP - 536

EP - 545

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 8

ER -