Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review

Fan Cao; Yi-Zi Li; De-Yu Zhang; Xiao-Ying Wang; Wen-Xiao Chen; Fang-Hua Liu; Yi-Xuan Men; Song Gao; Chun-Qing Lin; Hua-Chun Zou; Ting-Ting Gong; Qi-Jun Wu

doi:10.1016/j.ebiom.2024.105155

Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review

EBioMedicine. 2024 May 13:104:105155. doi: 10.1016/j.ebiom.2024.105155. Online ahead of print.

Authors

Fan Cao¹, Yi-Zi Li¹, De-Yu Zhang², Xiao-Ying Wang², Wen-Xiao Chen³, Fang-Hua Liu¹, Yi-Xuan Men², Song Gao², Chun-Qing Lin⁴, Hua-Chun Zou⁵, Ting-Ting Gong⁶, Qi-Jun Wu⁷

Affiliations

¹ Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China.
² Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
³ Department of Sports Medicine and Joint Surgery, The People's Hospital of Liaoning Province, Shenyang, China.
⁴ National Clinical Research Center for Cancer, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: lincq@cicams.ac.cn.
⁵ School of Public Health, Fudan University, Shanghai, China; Kirby Institute, University of New South Wales, Sydney, Australia. Electronic address: zouhuachun@fudan.edu.cn.
⁶ Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China. Electronic address: gongtt@sj-hospital.org.
⁷ Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Advanced Reproductive Medicine and Fertility (China Medical University), National Health Commission, Shenyang, China. Electronic address: wuqj@sj-hospital.org.

Abstract

Background: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations.

Methods: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070).

Findings: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer.

Interpretation: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease.

Funding: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

Keywords: Cancer; Human papillomavirus; Observational study; Risk; Umbrella review.