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

Sep 21, 2026

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Human papillomavirus (HPV) infection has been studied for links to cancer risk at specific sites beyond the anogenital tract and oropharyngeal region, yet results are inconsistent and the evidence quality has not been systematically quantified. An umbrella review of systematic reviews and meta-analyses of observational studies was conducted, assessing methodology with AMSTAR and evidence credibility with GRADE. The review synthesized updated estimates and identified convincing and highly suggestive HPV–cancer associations.

LanguageEnglish

CategoryResearch & Report

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Pages14

Reading Time35 min

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Articles Human papillomavirus infection and the risk of cancer at speciﬁc sites other than anogenital tract and oropharyngeal region: an umbrella review Fan Cao,a,b,c,j Yi-Zi Li,a,b,c,j De-Yu Zhang,d,j Xiao-Ying Wang,d,j Wen-Xiao Chen,e Fang-Hua Liu,a,b,c Yi-Xuan Men,d Song Gao,d Chun-Qing Lin,f,∗∗ Hua-Chun Zou,g,h,∗ Ting-Ting Gong,d,∗∗∗ and Qi-Jun Wua,b,c,d,i,∗∗∗∗ aDepartment of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China bClinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China cKey Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China dDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China eDepartment of Sports Medicine and Joint Surgery, The People’s Hospital of Liaoning Province, Shenyang, China fNational Clinical Research Center for Cancer, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China gSchool of Public Health, Fudan University, Shanghai, China hKirby Institute, University of New South Wales, Sydney, Australia iNHC Key Laboratory of Advanced Reproductive Medicine and Fertility (China Medical University), National Health Commission, Shenyang, China Summary 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. *Corresponding author. School of Public Health, Fudan University, Shanghai, China. **Corresponding author. National Clinical Research Center for Cancer, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. ***Corresponding author. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China. ****Corresponding author. Department of Clinical Epidemiology, Department of Obstetrics and Gynecology, Clinical Research Center, Key Laboratory of P

FAQs

What is the goal of this umbrella review?

To summarize existing evidence on HPV infection and the risk of specific cancers outside the anogenital tract and oropharyngeal region, and to assess the strength and credibility of these associations.

How were the studies selected and evaluated?

Eligible studies included systematic reviews and meta-analyses of observational evidence examining HPV or HPV-associated genotypes and specific cancers; methodology was evaluated with AMSTAR and evidence credibility with GRADE.

Which HPV–cancer associations were rated as most convincing or highly suggestive?

The review found one convincing association: HPV-18 infection increased breast cancer risk. Highly suggestive outcomes included oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, lung cancer, and additional breast cancer signals.

Sep 21, 2026

Uploaded by Eliana