European Journal of Gynaecological Oncology. 2026; 47(2): 1-4. doi: 10.22514/ejgo.2026.011
Editorial

HPV & co. in sporadic breast cancer: any connection?

Luca Roncati1,2,*,, Yisheng Chen3

1Department of Life Sciences, Health, and Health Care Professions, School of Medicine and Surgery, Link Campus University, 00165 Rome, Italy

2Department of Women’s Health, European Institute of Dermatology, 20137 Milan, Italy

3Department of Vascular and Interventional Radiology, Municipal Hospital of Ningde Normal University, 352100 Ningde, Fujian, China

*Corresponding Author(s):l.roncati@unilink.it (Luca Roncati)

History Submitted: 25 December 2025 | Accepted: 30 December 2025 | Published: 15 April 2026
Copyright:  ©2026 The Author(s). Published by MRE Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

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Abstract

No abstract available.

Keywords:Breast cancer;Oncoviruses;Human mammary tumor virus (HMTV);Human papillomavirus (HPV);Epstein-Barr virus (EBV);Cytomegalovirus (CMV);Polyomaviruses
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Cite this article

Luca Roncati, Yisheng Chen. HPV & co. in sporadic breast cancer: any connection?. European Journal of Gynaecological Oncology. 2026; 47(2): 1-4. doi: 10.22514/ejgo.2026.011

Breast cancer is the most common malignancy worldwide and the leading cause of cancer death in women [1]. Risk factors include advanced age, hormone replacement therapy, endocrine disruptors, obesity, cigarette smoking, and alcohol abuse; hence the importance of lifestyle, together with pollution and genetic predisposition [2]. Women with mutations in the breast cancer antigen (BRCA) or partner and locator BRCA (PALB) genes have in fact a lifetime risk of developing breast cancer of around 70% and 30%, respectively [3].

Over the years, it has been suspected that some oncovirus may play a role in human sporadic breast cancer, by analogy to what happens in mice, where mouse mammary tumor virus (MMTV) is an established etiological factor [4]. In 2001, the human homologue of MMTV, that is the human mammary tumor virus (HMTV), has been isolated, and this discovery is taken as evidence to support the concept according to which viral origin of specific forms of breast cancer is at least possible also in humans [5].

Today, eight human oncoviruses are widely recognized (Table 1), among which in particular human papillomavirus (HPV), Epstein-Barr virus and cytomegalovirus have been found capable to infect mammary cells [6, 7, 8, 9, 10, 11]. Their presence has been detected more frequently in tumor tissues than in healthy ones [12], and they are often present at the same time [13, 14, 15, 16, 17], even in milk [18, 19]. Some authors have highlighted their co-existence in the triple-negative subtype, the most aggressive and least curable subtype of breast cancer [20, 21, 22, 23].

Table 1.Names, acronyms, and associated cancers of the eight known human oncoviruses to date.
Virus NameAcronymAssociated Cancer
Hepatitis B VirusHBVHepatocellular carcinoma
Hepatitis C VirusHCVHepatocellular carcinoma
Human Herpes Virus 4
Alias Epstein-Barr Virus		HHV4
EBV		Nasopharyngeal carcinoma, lymphoma and leukemia
Human Herpes Virus 5
Alias Cytomegalovirus		HHV5
CMV		Mucoepidermoid carcinoma
Human Herpes Virus 8
Alias Kaposi’s Sarcoma-Associated Herpesvirus		HHV8
KSHV		Kaposi’s sarcoma and lymphoma
Human PapillomavirusHPVSquamous cell carcinoma
Human T-Lymphotropic VirusHTLVLeukemia
Merkel Cell PolyomavirusMCVMerkel cell carcinoma

As regards HPV, similarly to what occurs in the gynecological, anogenital or head and neck districts [24], the strains found are those at high risk, first and foremost HPV16, HPV18 and HPV33 [25, 26, 27]. In vitro, early (E) proteins E6 and E7 of HPV16 promote proliferation and invasion of human breast cancer cell lines, both enhanced by B-cell lymphoma 2 (BCL2) overexpression and BRCA1 and protein 53 downregulation [28, 29, 30]. Furthermore, elevated levels of interleukin-6 has been observed in patients with HPV-positive breast cancer [31].

Case series of possible HPV involvement come from all over the world, from Japan [32], Korea [33], China [27, 29, 34], Taiwan [35], Pakistan [36], Iran [10, 37], Iraq [38], Syria [15, 39], Jordan [13], Egypt [40, 41], Qatar [14], Ethiopia [42], Algeria [22], and Morocco [43], to Mexico [44], Peru [45, 46], Chile [16], and Brazil [47], passing through Italy [23], Spain [48], and the United Kingdom [49]. Interestingly, in a small cohort of Mexican women, HPV has been reported in the metaplastic variant, characterized by the differentiation of the neoplastic epithelium in particular towards squamous cells, the notorious target of the virus [50]. An Italian research group has also identified HPV in the papillary variant of breast cancer, a typical histopathology associated with HPV infection [51]. According to other authors, the presence of koilocytes would indicate a role of HPV in breast cancer [52].

In the English literature, there is only one publication dating back to 2015 conducted in Iran on 100 female patients affected by breast cancer, which evaluated the presence of Merkel cell polyomavirus (MCV) and found it in 3% [53].

Afterwards, attention has shifted to polyomavirus strains other than MCV, particularly the strains BK and JC (from the initials of the two patients—Babikir Kurdi and John Cunningham—from whom they were first isolated) [54]. In 1953, the virologist Ludwik Gross experimented that by inoculating mice with a filterable agent recovered from leukemic extracts, a multiple (poly-) carcinoma (-oma) was induced in the parotid gland; this agent was later traced back to murine polyomavirus [55]. Therefore, the oncogenic power of specific polyomavirus strains even in humans should not be surprising.

Given this complex and piecemeal scenario, a connection between oncoviruses and some subtypes of sporadic breast cancer appears worthy of further investigation, as does the possibility that superimposed viral infections may be a trigger for the transition from an indolent to an aggressive form.

Abbreviations

BRCA, breast cancer antigen; PALB, partner and locator BRCA; MMTV, mouse mammary tumor virus; HMTV, human mammary tumor virus; HPV, human papillomavirus; E, early; BCL2, B-cell lymphoma 2; MCV, Merkel cell polyomavirus; BK, Babikir Kurdi; JC, John Cunningham; EBV, Epstein-Barr virus; CMV, cytomegalovirus.

Availability of Data and Materials

Data sharing is not applicable to this article, as no datasets were generated or analyzed during the current study.

Author contributions

LR—designed the research study; performed the research; analyzed the data; wrote the manuscript. YSC—provided help and advice on validation, editing, and visualization. Both authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Acknowledgment

Not applicable.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest. Luca Roncati is serving as one of the Editorial Board members of this Journal. Full responsibility for the editorial process for this article was delegated to EH.

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