HPV-positive cancers at uncommon sites - a narrative review

Sep 22, 2026

Uploaded by Rhys

Human papillomavirus (HPV) is a common sexually transmitted infection that primarily targets anogenital and oropharyngeal mucosa, most notably the uterine cervix. Beyond these typical locations, HPV-positive cancers can arise in less common sites such as the vagina, vulva, anus, and penis, and HPV is sometimes detected in other malignancies with unclear clinical significance. This narrative review synthesizes evidence on these uncommon HPV-positive cancers, highlighting HPV genotype distribution and key methodological pitfalls.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

HPV carcinogenicity

TYPE Review PUBLISHED 11 March 2026 DOI 10.3389/or.2026.1737332 OPEN ACCESS EDITED BY Maria Isaguliants, Riga Stradiņš University, Latvia REVIEWED BY Elena V. Kashuba, National Academy of Sciences of Ukraine (NAN Ukraine), Ukraine Alina Sultanova, Riga Stradiņš University, Latvia Daria Avdoshina, Chumakov Federal Scientific Center for Research and Development of Immuneand-Biological Products (RAS), Russia *CORRESPONDENCE Lorenzo Agoni, [lorenzo.agoni@poliambulanza.it](lorenzo.agoni@poliambulanza.it) RECEIVED 01 November 2025 REVISED 06 February 2026 ACCEPTED 17 February 2026 PUBLISHED 11 March 2026 CITATION Agoni L, Spahiu O and Blakaj DM (2026) HPV-positive cancers at uncommon sites: a narrative review. Oncol. Rev. 20:1737332 . doi: 10.3389/or.2026.1737332 COPYRIGHT © 2026 Agoni, Spahiu and Blakaj. 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. HPV-positive cancers at uncommon sites: a narrative review Lorenzo Agoni 1*, Orges Spahiu 2 and Dukagjin M. Blakaj 3 1Unit of Obstetrics and Gynecology, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy, 2Radiation Therapy Unit, Mother Teresa University Hospital Center, Tirana, Albania, 3Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States Human papillomavirus (HPV) usually infects the anogenital and the oropharyngeal areas. HPV may lead to cancer at these sites, most notably at the uterine cervix. Less frequently, vaginal, vulvar, anal and penile cancers may also arise. HPV maybe also found, sometimes, in other cancers, such as lung, breast, bladder, esophageal cancers and others, which are not typical sites for HPV-related cancers. HPV spreads easily throughout the body and it has an intrinsic carcinogenic potential, which it may operate on organs which are distant from the genital area, although with a limited incidence of disease. It has been debated whether such occurrence has a casual or causative significance. In this systematic review we summarize the evidence and the pitfalls of these uncommon HPVpositive cancers, with particular emphasis on HPV genotypes distribution. KEYWORDS cancer, genotypes, HPV, papillomavirus (HPV), uncommon sites 1 Introduction Human papillomavirus (HPV) infection, which is the most common sexually transmitted infection worldwide, usually targets organs at the anogenital area and organs of the head and neck area, which are those involved in sexual intercourse and where mucous epithelia, which are the target of the virus, are found. The actual incidence of the infection is unknown, but it is estimated that approximately 80%–90% ofpeople get infected by HPV at least once within the 45 years of age ( 1). The prevalence of the infection accounts to an average of 11,7% worldwide but may vary according to country and age groups, ranging from approximately 1% in some regions of Asia to over 30% in some regions of Africa (2). HPV is a well-known carcinogenic agent and it’s the major determinant of cervical cancer. Likely, 98%–100% of cervical cancers depend on HPV infection. According to the“Human Papillomavirus and related diseases Report” (2) issued by IARC in 2023, approximately 600,000 new cases of cervical cancer are diagnosed every year globally. Also, HPV may cause cancer in other organs of the anogenital and head and neck areas. While we can count 280,000 oral cavity cancers, 180,000 laryngeal cancers, 140,000 oropharyngeal cancers, 44,000 vulvar cancers, 34,000 penile cancers, 29,000 anal cancers, 18,000 vaginal can

FAQs

Which cancer sites are considered typical for HPV-related malignancy?

HPV usually infects the anogenital and oropharyngeal areas, with uterine cervix cancer as the most notable outcome.

Why is the significance of HPV found in other cancers still debated?

The review notes debate over whether HPV presence in non-typical cancers has causal significance, as incidence is limited and relationships are not fully elucidated.

What genotype groups are mentioned for HPV carcinogenicity?

The text reports IARC classification: carcinogenic Group 1 genotypes, probably carcinogenic Group 2A, and possible carcinogenic Group 2B, with other genotypes generally considered not carcinogenic.

Sep 22, 2026

Uploaded by Rhys