Squamous cell anal cancer: Management and therapeutic options

Pessia, Beatrice; Romano, Lucia; Giuliani, Antonio; Lazzarin, Gianni; Carlei, Francesco; Schietroma, M

doi:10.1016/j.amsu.2020.04.016

Cited by 37 publications

(51 citation statements)

References 85 publications

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“…Five-year survival estimates are 70–80%, although significant morbidity is associated with post-surgical wound complications. In the 10–20% of patients who present with metastatic disease, 5-year survival decreases to below 20%, emphasizing the importance of early diagnosis and treatment [1, 6, 7, 9, 12].…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…Again, although the dominant aetiology of AC is the HPV infection, it does not confirm the viral presence. Finally, other than the debunking surgery, any other therapy was not available, although the gold standard approach includes chemotherapy plus radiotherapy [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

“…The majority are squamous cell carcinomas, whereas non-squamous include adenocarcinomas and melanomas [ 1 ]. AC risk factors include human papillomavirus (HPV) infection, history of sexually transmitted diseases (STDs) or of vulvar or cervical carcinoma, human immunodeficiency virus (HIV) immunosuppression or other forms of immunosuppression, haematological or immunological disorders and smoking [ 2 ]. It is estimated that 90% of anal squamous cancers are related to HPV and, in particular, HPV-16 is associated with >75% of these cancers [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…AC risk factors include human papillomavirus (HPV) infection, history of sexually transmitted diseases (STDs) or of vulvar or cervical carcinoma, human immunodeficiency virus (HIV) immunosuppression or other forms of immunosuppression, haematological or immunological disorders and smoking [ 2 ]. It is estimated that 90% of anal squamous cancers are related to HPV and, in particular, HPV-16 is associated with >75% of these cancers [ 2 ]. Interestingly, many studies reported a high rate of anal HPV in HIV-infected women with most reporting prevalence rates >70% [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Anal high-grade and late-stage cancer management in low-income setting: a case report

Colangelo

Pizzol²,

Antunes

2020

Journal of Surgical Case Reports

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The burden of cancer is increasing in sub-Saharan Africa due to ageing, common risk factors and population growth. Anal cancer is a human papillomavirus-related rare disease with an incidence rate of 1.8 per 100 000 persons overall with an increasing incidence of by 2% per year in the last three decades. Despite that gold standard management is well described, in low-income countries, there is no possibility for a proper management. We presented a late-stage anal cancer case that reflects the urgent necessity to create the adequate condition for the development of effective oncologic approach including prevention, diagnosis and management.

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“…Rates of ASCC in the general population are low, at less than 2 per 100,000 person years, with slightly higher rates in women compared with men 4 . Incidence has been steadily increasing over the past three decades 5 although, recent data has suggested ASCC in people with HIV have decreased over the past decade (2008–2012), thought to be due to improved HIV treatments 6 .…”

Section: Introductionmentioning

confidence: 87%

Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia

Phillips

Cassells

Garland

et al. 2022

Sci Rep

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Human papillomavirus (HPV) is detected in up to 96% of anal squamous cell cancers, where screening programs needed. However, the best methodology is still undetermined. Host DNA methylation markers CADM1, MAL and miR124 have been identified in cervical disease, but not anal disease. Anal swabs varying by disease grade were assessed for DNA methylation of CADM1, MAL and miR124-2. Each marker was compared across disease grades, stratified by HPV and HIV status. Receiver operating characteristic curves identified the predictive value of significant gene candidates. CADM1 methylation was significantly higher in high-grade squamous intraepithelial lesions (HSIL) compared with low-grade (LSIL) (p = 0.005) or normal (p < 0.001) samples with 67.2% correctly identified as HSIL. MAL methylation was significantly (p = 0.002) increased in HSIL compared with LSIL in HIV positive participants with 79.8% correctly indicated as HSIL. Gene miR124-2, showed no difference between disease grades. Biomarkers with established diagnostic value in cervical disease have limited utility in the prediction of anal disease, with CADM1 identified as a marker with screening potential in a gay and bisexual men (GBM) population and MAL in HIV positive GBM population. New markers specific to the anal mucosa are required to improve triage of high-risk individuals.

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Squamous cell anal cancer: Management and therapeutic options

Cited by 37 publications

References 85 publications

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

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

Anal high-grade and late-stage cancer management in low-income setting: a case report

Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia

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