Genetic Association Between High‐Risk HPV (HPV16 and HPV18) Infection and Tumor Development: A Mendelian Randomization Analysis

ABSTRACT Background and Aims Observational and experimental studies have provided substantial evidence supporting a link between cervical cancer and human papillomavirus (HPV) infection. Nevertheless, there is uncertainty regarding the association of benign and malignant cancers with HPV infection....

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Main Authors: You Wu, Haiyang Xia, Feng Du, Jian Zhang, Xulin Jiang, Jun Tang, Zhihong Li
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Health Science Reports
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Online Access:https://doi.org/10.1002/hsr2.70704
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author You Wu
Haiyang Xia
Feng Du
Jian Zhang
Xulin Jiang
Jun Tang
Zhihong Li
author_facet You Wu
Haiyang Xia
Feng Du
Jian Zhang
Xulin Jiang
Jun Tang
Zhihong Li
author_sort You Wu
collection DOAJ
description ABSTRACT Background and Aims Observational and experimental studies have provided substantial evidence supporting a link between cervical cancer and human papillomavirus (HPV) infection. Nevertheless, there is uncertainty regarding the association of benign and malignant cancers with HPV infection. Methods The study was divided into two approaches, Mendelian randomization (MR) and multivariate Mendelian randomization (MVMR), to investigate the link between HPV and both benign and malignant cancers. This study employed genetic variants as instrumental variables to mitigate potential biases arising from confounding factors and reverse causality. In 338 cases and 1000 controls in the European ancestry of Germany, independent genetic variations were identified as having a substantial correlation (p < 5 × 10−5) with exposure and HPV infection. The outcome variables data of various carcinomas were acquired from the Genome‐wide association summary data. Meanwhile, benign tumors from the FinnGen and UK Biobank (UKB) consortium were acquired as well. Results Following correction for multiple testing, the MVMR method was employed and the causal association was investigated between genetic liability to HPV infection and various malignancies, including bone and articular cartilage, bladder cancer, secondary malignant neoplasm of the liver, prostate cancer, as well as benign tumors including melanocytic naevi of the lip, brain, bronchus and lung, lip, mouth and pharynx, pancreas, and haemangioma and lymphangioma, and female genitalia. Conclusions From a genetic standpoint, HPV may contributes to the formation of benign and malignant tumors in female genital cancer as well as malignancies in other regions of the body, which should inform public health policy.
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spelling doaj-art-e23536fc2ef84fc5a81e556d51885b442025-08-20T02:11:03ZengWileyHealth Science Reports2398-88352025-04-0184n/an/a10.1002/hsr2.70704Genetic Association Between High‐Risk HPV (HPV16 and HPV18) Infection and Tumor Development: A Mendelian Randomization AnalysisYou Wu0Haiyang Xia1Feng Du2Jian Zhang3Xulin Jiang4Jun Tang5Zhihong Li6Department of Gastrointestinal Surgery Ezhou Central Hospital, Affiliated to Hubei University of Science and Technology Ezhou Hubei People Republic of ChinaDepartment of Gastrointestinal Surgery Ezhou Central Hospital, Affiliated to Hubei University of Science and Technology Ezhou Hubei People Republic of ChinaDepartment of Gastrointestinal Surgery Ezhou Central Hospital, Affiliated to Hubei University of Science and Technology Ezhou Hubei People Republic of ChinaDepartment of Gastrointestinal Surgery Ezhou Central Hospital, Affiliated to Hubei University of Science and Technology Ezhou Hubei People Republic of ChinaDepartment of Gastrointestinal Surgery Ezhou Central Hospital, Affiliated to Hubei University of Science and Technology Ezhou Hubei People Republic of ChinaDepartment of Gastrointestinal Surgery Ezhou Central Hospital, Affiliated to Hubei University of Science and Technology Ezhou Hubei People Republic of ChinaDepartment of Gastrointestinal Surgery Ezhou Central Hospital, Affiliated to Hubei University of Science and Technology Ezhou Hubei People Republic of ChinaABSTRACT Background and Aims Observational and experimental studies have provided substantial evidence supporting a link between cervical cancer and human papillomavirus (HPV) infection. Nevertheless, there is uncertainty regarding the association of benign and malignant cancers with HPV infection. Methods The study was divided into two approaches, Mendelian randomization (MR) and multivariate Mendelian randomization (MVMR), to investigate the link between HPV and both benign and malignant cancers. This study employed genetic variants as instrumental variables to mitigate potential biases arising from confounding factors and reverse causality. In 338 cases and 1000 controls in the European ancestry of Germany, independent genetic variations were identified as having a substantial correlation (p < 5 × 10−5) with exposure and HPV infection. The outcome variables data of various carcinomas were acquired from the Genome‐wide association summary data. Meanwhile, benign tumors from the FinnGen and UK Biobank (UKB) consortium were acquired as well. Results Following correction for multiple testing, the MVMR method was employed and the causal association was investigated between genetic liability to HPV infection and various malignancies, including bone and articular cartilage, bladder cancer, secondary malignant neoplasm of the liver, prostate cancer, as well as benign tumors including melanocytic naevi of the lip, brain, bronchus and lung, lip, mouth and pharynx, pancreas, and haemangioma and lymphangioma, and female genitalia. Conclusions From a genetic standpoint, HPV may contributes to the formation of benign and malignant tumors in female genital cancer as well as malignancies in other regions of the body, which should inform public health policy.https://doi.org/10.1002/hsr2.70704cancersHPVhuman papillomavirusMendelian randomizationneoplasms
spellingShingle You Wu
Haiyang Xia
Feng Du
Jian Zhang
Xulin Jiang
Jun Tang
Zhihong Li
Genetic Association Between High‐Risk HPV (HPV16 and HPV18) Infection and Tumor Development: A Mendelian Randomization Analysis
Health Science Reports
cancers
HPV
human papillomavirus
Mendelian randomization
neoplasms
title Genetic Association Between High‐Risk HPV (HPV16 and HPV18) Infection and Tumor Development: A Mendelian Randomization Analysis
title_full Genetic Association Between High‐Risk HPV (HPV16 and HPV18) Infection and Tumor Development: A Mendelian Randomization Analysis
title_fullStr Genetic Association Between High‐Risk HPV (HPV16 and HPV18) Infection and Tumor Development: A Mendelian Randomization Analysis
title_full_unstemmed Genetic Association Between High‐Risk HPV (HPV16 and HPV18) Infection and Tumor Development: A Mendelian Randomization Analysis
title_short Genetic Association Between High‐Risk HPV (HPV16 and HPV18) Infection and Tumor Development: A Mendelian Randomization Analysis
title_sort genetic association between high risk hpv hpv16 and hpv18 infection and tumor development a mendelian randomization analysis
topic cancers
HPV
human papillomavirus
Mendelian randomization
neoplasms
url https://doi.org/10.1002/hsr2.70704
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