The immune microenvironment of HPV-associated cancers: from viral oncogenesis to immunotherapy response

Sep 22, 2026

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Human papillomavirus (HPV) is an oncogenic DNA virus whose persistent high-risk infections drive malignant transformation across multiple tissues, producing distinct HPV-associated cancers. This review analyzes the tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC) and squamous cell carcinoma of the uterine cervix (CESC). It describes immune-cell composition and functional states, links immune features to prognosis, compares similarities and differences between HNSCC and CESC TME, and summarizes current and emerging therapeutic strategies for HPV-associated tumors.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

HPV infection and carcinogenesis

Prognostic impact of immune cell populations in HPV-associated HNSCC

TYPE Review PUBLISHED 01 May 2026 DOI 10.3389/fimmu.2026.1813400 OPEN ACCESS EDITED BY Shaheen Mowla, University of Cape Town, South Africa REVIEWED BY Chen Feng, Shandong University, China Maaweya Awadalla, King Fahd Medical City, Saudi Arabia *CORRESPONDENCE Kl´ara Plaˇckov´a [plackova@sotio.com](plackova@sotio.com) RECEIVED 18 February 2026 REVISED 12 April 2026 ACCEPTED 14 April 2026 PUBLISHED 01 May 2026 CITATION Plaˇckov´a K and Fialov´a A (2026) The immune microenvironment of HPV-associated cancers: from viral oncogenesis to immunotherapy response. Front. Immunol. 17:1813400 . doi: 10.3389/fimmu.2026.1813400 COPYRIGHT © 2026 Plaˇckov´a and Fialov´a . This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The immune microenvironment of HPV-associated cancers: from viral oncogenesis to immunotherapy response Kl´ara Plaˇckov´a1,2* and Anna Fialov´a1 1Sotio Biotech a.s., Prague, Czechia, 2 Department of Otorhinolaryngology, Head and Neck Surgery, First Faculty of Medicine, Charles University and University Hospital Motol and Homolka, Prague, Czechia Human papillomavirus (HPV) is a DNA virus with oncogenic potential. Persistent infections with high-risk HPV genotypes can drive malignant transformation in multiple tissues, resulting in distinct HPV-associated cancers. This review providesan analysis of the tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC) and squamous cell carcinoma of uterine cervix (CESC) . First, we brieﬂy introduce the key aspects of HPV biology and the mechanisms of carcinogenesis. We focus on the composition and functional states of immune cells within tumor tissues, highlighting how speciﬁc immune cells inﬂuence disease progression and clinical outcomes. By linking immunological features to patient prognosis, we outline the similarities and differences between the TME of HNSCC and CESC. Additionally, this review summarizes the current standards of care and emerging therapeutic strategies for patients with HPV-associated tumors. Altogether, by providing recent advances in the understanding of theTME of HPV-associated tumors, this review highlights the potential of targeting immune components within the tumor microenvironment for therapeutic beneﬁt. KEYWORDS cervical cancer, head and neck cancer, HPV, immune cells, tumor microenvironment 1 Introduction Human papillomavirus (HPV) is an epitheliotropic virus associated with several malignancies, including cervical squamous cell carcinoma (CESC) and head and necksquamous cell carcinoma (HNSCC) . CESC remains the fourth most common cancer in women worldwide, with over 600,000 new cases and approximately 300,000 deaths annually. Despite the availability of highly effective prophylactic polyvalent HPV vaccines, mortality remains high in low- and middle-income countries owing to limited access to vaccination and healthcare. HNSCC affects both men and women, with an estimated 800,000 new cases annually, 30% of which are HPV-positive. HPV-associated HNSCC originates mostly in the tonsils and base of the tongue. Compared with HNSCC of other etiologies, patients with HPV-induced carcinomas have a better prognosis, which is signiﬁcantly associated with a favorable immune landscape of the tumor. This review focuses on the tumor microenvironment (TME) of HPV-driven CESC and HNSCC, Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) highlighting differences in immune cell populations, their composition, and their distribution within the tumor stroma and epithelium, and exp

FAQs

What is the main focus of this review?

The review focuses on the tumor microenvironment (TME) in HPV-associated cancers, especially head and neck squamous cell carcinoma (HNSCC) and uterine cervical squamous cell carcinoma (CESC), linking immune-cell features to progression and outcomes.

How does HPV infection relate to cancer development described in the document?

HPV preferentially infects basal epithelial stem cells, and its life cycle is tightly linked to cell differentiation, with persistent high-risk HPV infection enabling malignant transformation in multiple tissues.

Which cancer types are compared for TME similarities and differences?

The document compares the TME of HNSCC and CESC, emphasizing differences in immune cell populations, their distribution in tumor stroma and epithelium, and prognostic significance.

Sep 22, 2026

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