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. 2025 Mar-Apr;39(2):1134-1147.
doi: 10.21873/invivo.13918.

An Unexpected Relationship Between Human Papillomavirus and Head and Neck Squamous Cell Carcinoma: A Mendelian Randomization Study

Yong Feng #  1   2 , Juan Zhai #  1   3 , Tobias Vollkommer  4 , Martin Gosau  4 , Ralf Smeets  4   5 , Rico Rutkowski  4 , Jieheng Wu  6 , Liyuan Xiao  7 , Reinhard E Friedrich  4
Affiliations

An Unexpected Relationship Between Human Papillomavirus and Head and Neck Squamous Cell Carcinoma: A Mendelian Randomization Study

Yong Feng et al. In Vivo. 2025 Mar-Apr.

Abstract

Background/aim: Head and neck cancer (HNC) is the sixth most common type of cancer worldwide. While it is widely accepted that human papillomavirus (HPV) infection is a crucial risk factor for the development of this type of cancer, there is still a lack of support from large-scale studies. This article addresses this gap by comprehensively analyzing the causal relationship between HPV infection and head and neck cancer using Mendelian randomization methods.

Patients and methods: The HPV database was utilized to identify instrumental variables via the most enormous GWAS database search tool. The study examined five cancer groups of data of interest from the UK Biobank and three groups of cancer data from the GAME-ON network, all obtained from public databases. The causal relationship was estimated using various approaches, including IVW, weighted median, MR-Egger, simple mode, and weighted mode.

Results: The results indicated no causal relationship between HPV16/18 E7 proteins and head and neck cancer, oral cancer, oropharyngeal cancer, and laryngeal cancer, including UKB database and GEME-ON network. Furthermore, there was no heterogeneity or horizontal pleiotropy in the data.

Conclusion: The analysis does not support a causal relationship between HPV infection and HNC, as indicated by the lack of evidence linking HPV16/18 E7 proteins to the development of this cancer.

Keywords: Head and neck cancer; Mendelian randomization; causal effect; human papillomaviruses.

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Conflict of interest statement

The Authors declare no conflicts of interest in relation to this study.

Figures

Figure 1
Figure 1
The flowchart of the current two-sample MR study. HPV: Human Papillomavirus; GWAS: genome-wide association study; MR: Mendelian randomization.
Figure 2
Figure 2
Scatter plots for the causal association between HPV16 infection and head and neck cancer (HNC). A) HNC from UK Biobank; B) LC from UK Biobank; C) Oral and oropharyngeal cancer from UK Biobank; D) Oral cavity cancer from UK Biobank; E) Oropharyngeal cancer from UK Biobank; F) Oral and oropharyngeal cancer from GAME-ON; G) Oral cavity cancer from GAME-ON; H) Oropharyngeal cancer from GAME-ON.
Figure 2
Figure 2
Scatter plots for the causal association between HPV16 infection and head and neck cancer (HNC). A) HNC from UK Biobank; B) LC from UK Biobank; C) Oral and oropharyngeal cancer from UK Biobank; D) Oral cavity cancer from UK Biobank; E) Oropharyngeal cancer from UK Biobank; F) Oral and oropharyngeal cancer from GAME-ON; G) Oral cavity cancer from GAME-ON; H) Oropharyngeal cancer from GAME-ON.
Figure 3
Figure 3
Scatter plots for the causal association between HPV18 infection and head and neck cancer (HNC). A) HNC from UK Biobank; B) LC from UK Biobank; C) Oral and oropharyngeal cancer from UK Biobank; D) Oral cavity cancer from UK Biobank; E) Oropharyngeal cancer from UK Biobank; F) Oral and oropharyngeal cancer from GAME-ON; G) Oral cavity cancer from GAME-ON; H) Oropharyngeal cancer from GAME-ON.
Figure 3
Figure 3
Scatter plots for the causal association between HPV18 infection and head and neck cancer (HNC). A) HNC from UK Biobank; B) LC from UK Biobank; C) Oral and oropharyngeal cancer from UK Biobank; D) Oral cavity cancer from UK Biobank; E) Oropharyngeal cancer from UK Biobank; F) Oral and oropharyngeal cancer from GAME-ON; G) Oral cavity cancer from GAME-ON; H) Oropharyngeal cancer from GAME-ON.
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References

    1. Machiels JP, René Leemans C, Golusinski W, Grau C, Licitra L, Gregoire V, EHNS Executive Board, ESMO Guidelines Committee, ESTRO Executive Board Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS–ESMO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(11):1462–1475. doi: 10.1016/j.annonc.2020.07.011. - DOI - PubMed
    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Marur S, Forastiere AA. Head and neck cancer: Changing epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008;83(4):489–501. doi: 10.4065/83.4.489. - DOI - PubMed
    1. Lacas B, Carmel A, Landais C, Wong SJ, Licitra L, Tobias JS, Burtness B, Ghi MG, Cohen EEW, Grau C, Wolf G, Hitt R, Corvò R, Budach V, Kumar S, Laskar SG, Mazeron JJ, Zhong LP, Dobrowsky W, Ghadjar P, Fallai C, Zakotnik B, Sharma A, Bensadoun RJ, Ruo Redda MG, Racadot S, Fountzilas G, Brizel D, Rovea P, Argiris A, Nagy ZT, Lee JW, Fortpied C, Harris J, Bourhis J, Aupérin A, Blanchard P, Pignon JP, MACH-NC Collaborative Group Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiother Oncol. 2021;156:281–293. doi: 10.1016/j.radonc.2021.01.013. - DOI - PMC - PubMed
    1. Chung CH, Ely K, McGavran L, Varella-Garcia M, Parker J, Parker N, Jarrett C, Carter J, Murphy BA, Netterville J, Burkey BB, Sinard R, Cmelak A, Levy S, Yarbrough WG, Slebos RJ, Hirsch FR. Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol. 2006;24(25):4170–4176. doi: 10.1200/JCO.2006.07.2587. - DOI - PubMed

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