HPV-Induced Field Cancerisation: Transformation of Adult Tissue Stem Cell Into Cancer Stem Cell.

Carlotta Olivero,Simone Lanfredini,Cinzia Borgogna,Marisa Gariglio,Girish K Patel

doi:10.3389/fmicb.2018.00546

Carlotta Olivero, Simone Lanfredini + Show 3 more

Open Access

https://doi.org/10.3389/fmicb.2018.00546

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Abstract

Field cancerisation was originally described as a basis for multiple head and neck squamous cell carcinoma (HNSCC) and is a pre-malignant phenomenon that is frequently attributable to oncogenic human papillomavirus (HPV) infection. Our work on β-HPV-induced cutaneous squamous cell carcinomas identified a novel Lrig1+ hair follicle junctional zone keratinocyte stem cell population as the basis for field cancerisation. Herein, we describe the ability for HPV to infect adult tissue stem cells in order to establish persistent infection and induce their proliferation and displacement resulting in field cancerisation. By review of the HPV literature, we reveal how this mechanism is conserved as the basis of field cancerisation across many tissues. New insights have identified the capacity for HPV early region genes to dysregulate adult tissue stem cell self-renewal pathways ensuring that the expanded population preserve its stem cell characteristics beyond the stem cell niche. HPV-infected cells acquire additional transforming mutations that can give rise to intraepithelial neoplasia (IEN), from environmental factors such as sunlight or tobacco induced mutations in skin and oral cavity, respectively. With establishment of IEN, HPV viral replication is sacrificed with loss of the episome, and the tissue is predisposed to multiple cancer stem cell-driven carcinomas.

Highlights

Human papillomavirus (HPV) infection is associated with oropharyngeal and anogenital cancers in both men and women
90% of all cervical cancers are attributed to high-risk alpha-genus HPV (α-HPV) infections, ∼60% of squamous cell carcinomas (SCC) of the vulva, vagina, anus and penis are due to infection of α-HPV (Crow, 2012)
HPV infection is considered to be responsible for the rise in head and neck squamous cell carcinoma (HNSCC), in cancers of the oropharynx and base of tongue (Marur et al, 2010; Leemans et al, 2011)

Summary

INTRODUCTION

Human papillomavirus (HPV) infection is associated with oropharyngeal and anogenital cancers in both men and women. 90% of all cervical cancers are attributed to high-risk alpha-genus HPV (α-HPV) infections, ∼60% of squamous cell carcinomas (SCC) of the vulva, vagina, anus and penis are due to infection of α-HPV (Crow, 2012). HPV infection is considered to be responsible for the rise in head and neck squamous cell carcinoma (HNSCC), in cancers of the oropharynx and base of tongue (Marur et al, 2010; Leemans et al, 2011). Cutaneous HPVs, which are clustered in the evolutionarily distinct β-genus, have been associated with the development of cutaneous SCC, especially in the immunosuppressed setting (Howley and Pfister, 2015; Quint et al, 2015)

HPV and Field Cancerisation

FIELD CANCERISATION

HPV INFECTION AND STEM CELL EXPANSION

HPV INFECTION DRIVEN CANCER STEM CELLS

Findings

CONCLUSION