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Wessely, Anja; Heppt, Markus V.; Kammerbauer, Claudia; Steeb, Theresa; Kirchner, Thomas; Flaig, Michael J.; French, Lars E.; Berking, Carola; Schmoeckel, Elisa und Reinholz, Markus (2020): Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma. In: Cancers, Bd. 12, Nr. 9, 2516

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Abstract

Simple Summary Anal squamous cell carcinoma (SCC) is a rare cancer often caused by infection with high-risk human papillomavirus (HPV). Immune checkpoint blockade (ICB) targeting PD-1 or PD-L1 is successfully used for the treatment of other cancers as melanoma and lung cancer and might be an option for anal SCC as well. PD-L1 expression is associated with ICB outcome for example in melanoma. Here, we investigated whether infection with HPV affects PD-L1 expression and observed that almost two-thirds of anal SCC patients had PD-L1 positive tumors. Interestingly, these patients had a better median overall survival (OS). Sex, grade of differentiation, and HPV infection status did not influence the median OS. HPV infection status and PD-L1 expression were not correlated. Our findings indicate that PD-L1 is an independent prognostic marker in anal SCC. Besides, ICB targeting PD-1 or PD-L1 might be a therapy option for anal SCC patients irrespective of HPV infection status. Anal squamous cell carcinoma (SCC) is a rare cancer with increasing incidence. Infection with high-risk human papillomavirus (HPV) subtypes is the major cause for its development. We retrospectively analyzed tumor samples from 54 anal SCC patients for infection with a panel of 32 HPV subtypes in a PCR-based approach, determined the PD-L1 expression status, and correlated the findings with the clinical data and the survival of the patients. Forty-two patients (77.8%) were HPV-positive and harbored at least one carcinogenic HPV subtype. HPV16 was the most frequently detected (n = 39, 72.2%). Four patients were infected with multiple HPV subtypes. HPV infection was significantly more often detected in female than in male patients (90.3% vs. 60.9%, p = 0.018). Patients with PD-L1 positive tumors showed a significantly better median overall survival (OS) compared with patients with PD-L1 negative tumors (69.3 vs. 28.3 months, p = 0.006). The median OS was significantly different among the distinct tumor stages (p = 0.029). Sex, grade of differentiation, and HPV infection status did not influence the median OS. Furthermore, HPV infection status and PD-L1 expression were not correlated. A multivariate Cox regression analysis revealed that PD-L1 expression status was an independent prognostic marker for survival (p = 0.012).

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