HPV in breast cancer: prevalence and comparison with healthy tissue-a systematic review and meta-analysis
Clinical Snapshot
PICO Framework
| P — Population | Women with histologically confirmed breast cancer (BC) tissue samples, compared with women with healthy/non-cancerous breast tissue controls |
| I — Intervention | Detection of Human Papillomavirus (HPV) in breast cancer tissue specimens using molecular or immunohistochemical methods |
| C — Comparator | Healthy breast tissue controls (non-cancerous specimens) |
| O — Outcomes | Primary: prevalence of HPV in BC tissue; Secondary: odds ratio (OR) of HPV detection in BC versus healthy controls, stratified by continent, income classification, and BC molecular subtype |
Bottom Line
This meta-analysis of 82 studies and 7,683 breast cancer tissue samples estimates an overall HPV prevalence of 23% in BC specimens, with a fivefold increased odds of HPV detection in cancer versus healthy breast tissue (OR 5.06, P < 0.001). The association is statistically robust across both case-control and cross-sectional study designs and is most pronounced in South American studies (OR 11.66). The luminal B subtype showed the highest HPV positivity rate at 44%. However, several critical methodological limitations temper these findings: no GRADE certainty assessment was applied, risk of bias tools are not described, prediction intervals are absent, and publication bias assessment is not reported. Crucially, the extreme variability in HPV detection methods across primary studies (PCR, IHC, ISH) represents a fundamental source of heterogeneity that likely inflates and distorts pooled estimates. Causality cannot be established from observational prevalence data. These findings are hypothesis-generating and do not support any change to current breast cancer screening, prevention, or treatment protocols. Australian clinicians should note that HPV testing in breast tissue has no current TGA-approved indication, PBS listing, or RACGP guideline endorsement. Well-designed prospective studies with standardised HPV detection methodology are needed before clinical translation can be considered.
Key Findings
P Value: Overall OR P < 0.001; case-control OR P < 0.001; cross-sectional OR P < 0.001; South America OR P = 0.005
Effect Size: OR 5.06 for HPV detection in BC versus healthy breast tissue controls; case-control subgroup OR 6.34; cross-sectional subgroup OR 2.83; South America subgroup OR 11.66; Luminal B BC subtype HPV prevalence 44% (95% CI: 27%–61%); Oceania highest regional prevalence at 38%; Low-income countries prevalence 34% (95% CI: 9%–73%)
Primary Outcome: Overall HPV prevalence in breast cancer tissue samples: 23% (95% CI: 19%–28%) across 82 studies and 7,683 BC specimens
Nnt Or Sensitivity: Not applicable for this prevalence/association meta-analysis. No NNT calculable. Sensitivity/specificity of HPV detection methods not pooled. The OR of 5.06 suggests women with BC are approximately 5 times more likely to have HPV detected in tissue compared with healthy controls, though causality is not established.
Confidence Interval: Overall prevalence 95% CI: 19%–28%; OR overall 95% CI not explicitly stated in abstract; low-income subgroup 95% CI: 9%–73% (very wide, indicating high imprecision)
Clinical Application
At present, HPV testing in breast cancer tissue is not part of standard clinical workup and has no established diagnostic, prognostic, or therapeutic utility. Implementation of routine HPV testing in BC would require standardised, validated detection protocols — which this meta-analysis highlights as currently lacking. The findings are hypothesis-generating only. In Australia, breast cancer is the most commonly diagnosed cancer in women, with approximately 20,640 new cases estimated in 2024 (AIHW). Australia has one of the world's most successful HPV vaccination programs (National Immunisation Program, Gardasil 9, funded since 2007 for females and 2013 for males), achieving high population coverage. The relevance of HPV vaccination to BC prevention cannot be inferred from this meta-analysis. The TGA has not approved any HPV-related indication for BC diagnosis or treatment. RACGP guidelines do not currently recommend HPV testing in BC workup. The Oceania subgroup showing the highest regional HPV prevalence (38%) is noteworthy for Australian clinicians, though this likely reflects study-level heterogeneity rather than a true population signal. PBS-listed treatments for BC (e.g., trastuzumab, pertuzumab, CDK4/6 inhibitors) are unaffected by these findings. This evidence does not support any change to current Australian BC screening (BreastScreen Australia) or management pathways. Women with breast cancer across diverse geographic and socioeconomic settings. Subgroup findings are most relevant to clinicians in South America and Oceania where regional HPV-BC associations appear strongest. The luminal B subtype finding (44% HPV prevalence) may be of particular interest to breast oncologists managing hormone receptor-positive/HER2-positive disease.
Abstract
INTRODUCTION: Breast cancer (BC) is the most common cancer among women worldwide, with over 2.3 million new cases annually. Recent studies suggest that Human Papillomavirus (HPV), a known oncogenic virus, may be involved in BC development. This study investigates HPV prevalence in BC samples and its potential role in tumorigenesis. METHODS: Random-effects meta-analyses were conducted to estimate raw proportions and odds ratio (OR), with 95% confidence intervals (CIs). Heterogeneity was assessed using I2. Statistical significance was set at p < 0.05. Analyses were performed in R 4.5.0 RESULTS: Our meta-analysis encompassed 82 studies and evaluated 7,683 breast cancer (BC) tissue samples to assess the presence of HPV. The overall prevalence of HPV in BC specimens was estimated at 23% (95%CI: 19%-28%). When stratified by continent, Oceania exhibited the highest regional prevalence at 38%. Comparative analysis between BC tissues and healthy controls revealed a significantly increased likelihood of HPV detection in the cancer group (OR 5.06; P < 0.001). This association remained statistically robust in both case-control (OR 6.34; P < 0.001) and cross-sectional designs (OR 2.83; P < 0.001). Among continents, South America demonstrated the most pronounced association (OR 11.66; P = 0.005). Subgroup analysis based on economic classification indicated that countries with low-income settings had the highest HPV prevalence (34%; 95%CI: 9%-73%). Evaluation by BC subtype revealed that luminal B had the highest HPV-positive rate (44%; 95%CI: 27%-61%). CONCLUSION: This meta-analysis reveals a global presence of HPV in BC and suggests a possible link. Further well-designed studies are needed to confirm its role in tumorigenesis.
References
- 1.de Souza Wagner, P. H., Matheus, G. T. F. U., Menegat, B. L. R. S., Menegat, A. L. R. S., Ribeiro, D. M., & de Moraes, F. C. A. (2026). HPV in breast cancer: prevalence and comparison with healthy tissue-a systematic review and meta-analysis. Cancer Causes & Control. https://doi.org/10.1002/cncr.30007
This content is for educational purposes for healthcare professionals only and does not constitute clinical advice. Clinical decisions should be based on individual patient assessment, current guidelines, and appropriate specialist consultation. Editorial Standards · Privacy Policy · Terms of Service