The High-Risk Human Papillomavirus Type Influences the Tissue Microenvironment in Cervical Intraepithelial Neoplasia Grade 2

High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18)...

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Bibliographic Details
Published in:Viruses 2023-09, Vol.15 (9), p.1953
Main Authors: Saito, Mayumi, Rajesh, Aarthi, Innes, Carrie, van der Griend, Rachael, Fitzgerald, Peter, Simcock, Bryony, Sykes, Peter, Hibma, Merilyn
Format: Article
Language:English
Subjects:
CD4 antigen
CD8 antigen
Cell cycle
Cell division
Cell growth
cervical precancer
Cervix dysplasia
Complications and side effects
Development and progression
Diagnosis
Dioxygenase
Foxp3 protein
high-risk types
Human papillomavirus
Immunization
Infections
Lesions
Lymphocytes
Lymphocytes T
Microenvironments
Papillomavirus infections
Proteins
Risk factors
Stroma
tissue microenvironment
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Summary:High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18) cervical intraepithelial neoplasia grade 2 lesions differed from other high-risk types (HPV ‘other’). Consistent with other studies, we found that progression to higher-grade disease was more frequent in HPV16/18 lesions when compared with HPV ‘other’ lesions. HPV16/18 lesions were significantly more likely to be indoleamine 2,3,-dioxygenase 1 (IDO1)-positive and were associated with reduced CD8 and FoxP3 T cells in the lesion. In the stroma, reduced Tbet- and CD32-positive cells and increased Blimp1-positive cells were significantly associated with HPV16/18 lesions when compared with HPV ‘other’ types. On analysis of the IDO1-positive tissues, lesional IDO1 was associated with significantly decreased numbers of CD4-, CD8-, and FoxP3-positive cells in the stroma compared with IDO1-negative tissues. These data suggest that IDO1 expression may impair infiltration of CD4, CD8, and FoxP3 cells into the stroma beneath the precancer lesion. Increased expression of IDO1 may contribute to immune avoidance and an increased frequency of disease progression in HPV16- and 18-positive lesions.
ISSN:1999-4915
1999-4915
DOI:10.3390/v15091953