Study: Anal intraepithelial neoplasia is a precursor lesion for anal squamous cell carcinomas

Oncotarget recently published "PD-1/PD-L1 expression in anal squamous intraepithelial lesions" which reported that the presence and distribution of CD8 lymphocytes and the presence of PD-1 lymphocytes and PD-L1 epithelial cells were assessed.

CD8 lymphocytes were observed more frequently in HSIL versus LSIL in the lamina propria or intra epithelial.

PD-1 lymphocytes were observed more frequently in HSIL versus LSIL.

There was no difference between HSIL and LSIL for PD-L1 epithelial cells.

Anal dysplastic lesions are accompanied by an inflammatory lymphocytic infiltrate expressing CD8 and PD-1, more frequent in high-grade lesions.

Anal intraepithelial neoplasia (AIN) is the precursor lesion for anal squamous cell carcinomas (ASCC)."

Dr. Margot Bucau, Hôpital Bichat-Claude Bernard

Dr. Margot Bucau from The Hôpital Bichat-Claude Bernard said, "Anal intraepithelial neoplasia (AIN) is the precursor lesion for anal squamous cell carcinomas (ASCC).

Since 2012, the Lower Anogenital Squamous Terminology recommended denomination for HPV-associated squamous lesions of the lower anogenital tract as low-grade and high-grade squamous intraepithelial lesion.

Oncogenic HPV infection plays a crucial role in developing both cervical and anal lesions, by the integration of the viral DNA into the epithelial cells and activation of oncogenic early proteins E6 and E7. This causes downregulation of suppressing tumor genes, especially TP53 and Rb, and upregulation of p16.

In the cervix, HPV related cancer often have increased infiltration by immune cell populations, including cytotoxic CD8 T cells, which correlates with better response to chemoradiotherapy and increased survival compared to immune-deprived tumors.

Moreover, p16 positive tumors were shown to present higher tumor-infiltrating lymphocytes density and better recurrence-free survival.

The Bucau Research Team concluded in their Oncotarget Research Paper, "our exploratory study highlights the interest of the PD-1/PD-L1 pathway in anal dysplasia and the importance to further explore the different mechanisms of immune microenvironment in the progression of anal intra epithelial lesion. It suggests the potential role of therapeutic molecules targeting the immune response to slow down the tumor progression in selected patients with HSIL."