Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer

Ferreiro-Iglesias, Aida; McKay, James; Brenner, Nicole; Virani, Shama; Lesseur, Corina; Gaborieau, Valérie; Ness, Andy R; Hung, Rayjean J.; Liu, Geoffrey; Diergaarde, Brenda; Olshan, Andrew F.; Hayes, Nancy S.; Weissler, Mark C.; Schroeder, Lea; Bender, Noemi; Pawlita, Michael; Thomas, Steve; Pring, Miranda; Dudding, Tom; Kanterewicz, Beatriz; Ferris, Robert L.; Thomas, Sera; Brhane, Yonathan; Díez-Obrero, Virginia; Milojevic, Maja; Smith-Byrne, Karl; Mariosa, Daniela; Herrero, Rolando; Boccia, Stefania; Cadoni, Gabriella; Lacko, Martin; Holcátová, Ivana; Ahrens, Wolfgang; Λάγιου, Παγώνα; Lagiou, Areti; Polesel, Jerry; Simonato, Lorenzo; Merletti, Franco; Healy, Claire M.; Hansen, Bo T.; Nygård, Mari; Conway, David I.; Wright, Sylvia; Macfarlane, Tatiana V.; Robinson, Max; Alemany, Laia; Agudo, Antonio; Znaor, Ariana; Amos, Christopher I.; Waterboer, Tim

doi:10.1038/s41467-021-26151-9

Cited by 13 publications

(9 citation statements)

References 52 publications

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“…Participants were considered HPV seropositive if either of these two criteria was met. 30 HPV serology was performed at the German Cancer Research Center (DKFZ, Heidelberg, Germany), and laboratory personnel was blinded to the disease status. For controls that were not assayed, we imputed their serostatus by random binomial draw with the overall probability of seropositivity (0.86%) estimated from controls who were assayed.…”

Section: Hpv Serology Assay and Genotypingmentioning

confidence: 99%

“…18 We computed a polygenic risk score (PRS) for head and neck cancer overall and separately for oral cavity cancer and oropharyngeal cancer. The PRS was estimated as the sum of the number of risk alleles one carries weighted by the log odds ratio derived from the GWAS studies reported to date except for eight variants in the HLA region that were identified using HPV-positive oropharyngeal cancer cases, 30 where the weights were calculated based on the present study participants.…”

Section: Hpv Serology Assay and Genotypingmentioning

confidence: 99%

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A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers

Budhathoki

Diergaarde

Liu

et al. 2023

Intl Journal of Cancer

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Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold‐out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92‐0.95 in men and AUC = 0.92, 95% CI = 0.88‐0.95 in women). The 5‐year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.

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Section: Hpv Serology Assay and Genotypingmentioning

confidence: 99%

Section: Hpv Serology Assay and Genotypingmentioning

confidence: 99%

A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers

Budhathoki

Diergaarde

Liu

et al. 2023

Intl Journal of Cancer

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“…While this gene has not previously been associated with head and neck cancer risk, germline variation in ARID5B has been implicated in acute lymphoblastic leukemia (ALL) [ 47 ], as well as treatment resistance and higher rates of relapse [ 48 ]. Genetic variants in ARID5B have also been linked to autoimmune diseases [ 49 , 50 ], suggesting that immune dysregulation may be a plausible pleiotropic mechanism at this locus, especially given the infectious etiology of oropharyngeal carcinoma [ 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of genetic susceptibility to multiple primary cancers through whole-exome sequencing in two large multi-ancestry studies

Cavazos

Kachuri²,

Graff³

et al. 2022

BMC Med

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Background Up to one of every six individuals diagnosed with one cancer will be diagnosed with a second primary cancer in their lifetime. Genetic factors contributing to the development of multiple primary cancers, beyond known cancer syndromes, have been underexplored. Methods To characterize genetic susceptibility to multiple cancers, we conducted a pan-cancer, whole-exome sequencing study of individuals drawn from two large multi-ancestry populations (6429 cases, 165,853 controls). We created two groupings of individuals diagnosed with multiple primary cancers: (1) an overall combined set with at least two cancers across any of 36 organ sites and (2) cancer-specific sets defined by an index cancer at one of 16 organ sites with at least 50 cases from each study population. We then investigated whether variants identified from exome sequencing were associated with these sets of multiple cancer cases in comparison to individuals with one and, separately, no cancers. Results We identified 22 variant-phenotype associations, 10 of which have not been previously discovered and were significantly overrepresented among individuals with multiple cancers, compared to those with a single cancer. Conclusions Overall, we describe variants and genes that may play a fundamental role in the development of multiple primary cancers and improve our understanding of shared mechanisms underlying carcinogenesis.

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“…HPV has emerged as a risk factor for HNSCC [ 100 ]. HPV-16 is the main pathogenic group in over 200 types of HPVs [ 101 ]. HPV-16 is an 8 kb virus, which consists of seven early genes (E1-E7) and two late genes (L1 and L2).…”

Section: The Interaction Of Various Components In Hnsccmentioning

confidence: 99%

The tumor ecosystem in head and neck squamous cell carcinoma and advances in ecotherapy

Gong

Bao

et al. 2023

Mol Cancer

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The development of head and neck squamous cell carcinoma (HNSCC) is a multi-step process, and its survival depends on a complex tumor ecosystem, which not only promotes tumor growth but also helps to protect tumor cells from immune surveillance. With the advances of existing technologies and emerging models for ecosystem research, the evidence for cell-cell interplay is increasing. Herein, we discuss the recent advances in understanding the interaction between tumor cells, the major components of the HNSCC tumor ecosystem, and summarize the mechanisms of how biological and abiotic factors affect the tumor ecosystem. In addition, we review the emerging ecological treatment strategy for HNSCC based on existing studies.

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Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer

Cited by 13 publications

References 52 publications

A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers

A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers

Assessment of genetic susceptibility to multiple primary cancers through whole-exome sequencing in two large multi-ancestry studies

The tumor ecosystem in head and neck squamous cell carcinoma and advances in ecotherapy

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