Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Wessely, Anja; Heppt, Markus V.; Kammerbauer, Claudia; Steeb, Theresa; Kirchner, Thomas; Flaig, Michael J.; French, Lars E.; Berking, Carola; Schmoeckel, Elisa; Reinholz, Markus

doi:10.3390/cancers12092516

Cited by 24 publications

(20 citation statements)

References 40 publications

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“…The high prevalence of HPV infection and HPV-16 genotype in our non-metastatic ASCC cohort are in agreement with previously reported studies [ 14 , [24] , [25] , [26] , [27] ]. A very low frequency of other high-risk (HPV-45, -18, -33) and low-risk (HPV-6/11) HPV genotypes were also described in other ASCC series [ 14 , 24 , 27 ]. HPV-6 and -11 were detected in three samples, confirming that low-risk HPV genotypes might be occasionally associated with anal cancer, as observed in a laser capture microdissection study [28] .…”

Section: Resultssupporting

confidence: 93%

“…4 b). These results showed that PD-L1 was a strong predictive and prognostic biomarker for ASCC in agreement with previous studies [ 27 , 34 ], and suggest that immune checkpoints inhibitors may be considered as molecular targeted therapy for non-metastatic ASCC cases. Finally, When HER2/Neu immunodetection was assessed, a single case of expression was detected in a patient without residual tumor after definitive CRT (1 out 79 cases) (Supplementary Fig.…”

Section: Resultssupporting

confidence: 92%

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A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma

Iseas¹,

Golubicki²,

Robbio³

et al. 2021

Translational Oncology

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Highlights High-risk HPV infection is less frequently detected in HIV-positive non-metastatic ASCC compared with HIV-negative cases. Mutational profile identified in the non-metastatic ASCC cohort revealed expected similarities with metastatic ASCC. High PD-L1 expression levels are associated with high CD3 and CD8 TIL density, complete response to treatment, and good survival outcome of ASCC patients. PD-L1 is a reliable predictive and prognostic biomarker that allows the stratification in low- vs. high-risk ASCC patients at their initial therapeutic approach.

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Section: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 92%

A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma

Iseas¹,

Golubicki²,

Robbio³

et al. 2021

Translational Oncology

View full text Add to dashboard Cite

show abstract

“…The current literature is mixed regarding the significance of the PD-1/PD-L1 axis in HPV-associated anal SCC. PD-L1 expression in anal SCC has been linked with increased disease recurrence and decreased survival [119, 120]. Similarly, PD-L1 expression has been linked to the progression of precancerous lesions [121].…”

Section: The Effect Of Hiv Coinfection On Antitumor Responsementioning

confidence: 99%

Human Immunodeficiency Virus Infection Promotes Human Papillomavirus-Mediated Anal Squamous Carcinogenesis: An Immunologic and Pathobiologic Review

et al. 2021

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Background: Anal squamous cell carcinoma (SCC) is a rare gastrointestinal malignancy with rising incidence, both in the United States and internationally. The primary risk factor for anal SCC is human papillomavirus (HPV) infection. However, there is a growing burden of disease in patients with human immunodeficiency virus (HIV) and HPV coinfection, with the incidence of anal SCC significantly increasing in this population. This is particularly true in HIV-infected men. The epidemiologic correlation between HIV-HPV coinfection and anal SCC is established; however, the immunologic mechanisms underlying this relationship are not well understood. Summary: HIV-related immunosuppression due to low circulating CD4+ T cells is one component of increased risk, but other mechanisms, such as the effect of HIV on CD8+ T lymphocyte tumor infiltration and the PD-1/PD-L1 axis in antitumor and antiviral response, is emerging as significant contributors. The goal of this article is to review existing research on HIV-HPV coinfected anal SCC and precancerous lesions, propose explanations for the detrimental synergy of HIV and HPV on the pathogenesis and immunologic response to HPV-associated cancers, and discuss implications for future treatments and immunotherapies in HIV-positive patients with HPV-mediated anal SCC. Key Messages: The incidence of anal squamous cell carcinoma is increased in human immunodeficiency virus (HIV)-infected patients, even in patients on highly active antiretroviral therapy. Locoregional HIV infection may enhance human papillomavirus oncogenicity. Chronic inflammation due to HIV infection may contribute to CD8+ T lymphocyte exhaustion by upregulating PD-1 expression, thereby blunting cytotoxic antitumor response.

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“…However, there is some inconsistency regarding the association between the PD-1/PD-L1 axis and anal SCC in HPV-infected patients. Some studies have reported that upregulated expression of PD-L1 is associated with the progression of precancerous lesions and, in the case of anal SCC, a reduced survival rate [ 54 , 55 ]. In contrast, it has been observed that PD-L1 expression is associated with improved outcome [ 14 ].…”

Section: The Role Of Pd-1/pd-l1 Axis In Hpv and Hiv Coinfectionmentioning

confidence: 99%

The Role of Inflammation in Anal Cancer

et al. 2022

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The aim of this article was to present a summary of the current resources available in the literature regarding the role of inflammation in anal cancer development. Anal cancer is relatively uncommon, accounting for about 2.7% of all reported gastrointestinal cancers in the United States. However, the importance of understanding the pathogenesis and risk factors for anal cancer has been recognized over the last several decades due to a noticed increase in incidence worldwide. Infections, autoimmune diseases, and inflammatory diseases of unknown etiology cause chronic inflammation that promotes tumorigenesis. The association between chronic inflammation and cancer development is widely accepted. It is based on different pathophysiological mechanisms that lead to cellular transformation and changes in immunological response, allowing tumor cells to avoid apoptosis and immune surveillance. However, there are still many molecular and cellular mechanisms that remain largely unexplored. Further studies on this topic could be of tremendous significance in elucidating anal cancer pathogenesis and developing immunotherapeutic approaches for its treatment.

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Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Cited by 24 publications

References 40 publications

A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma

A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma

Human Immunodeficiency Virus Infection Promotes Human Papillomavirus-Mediated Anal Squamous Carcinogenesis: An Immunologic and Pathobiologic Review

The Role of Inflammation in Anal Cancer

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