Research on Anal Squamous Cell Carcinoma

Anal canal and peri-anal squamous cell carcinomas (ASCCs) are relatively rare cancers that affect approximately 8000 patients per year in the United States [...]

Programmed Death Ligand-1 Expression Is Associated With Poorer Survival in Anal Squamous Cell Carcinoma

Context.— Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in invasive anal squamous cell carcinoma (ASCC). Objective.— To assess PD-L1 expression in patients with ASCC and correlate it with clinicopathologic factors and clinical outcomes. Design.— Fifty-one cases of ASCC were immunostained for PD-L1. PD-L1 expression by combined positive score and tumor proportion score was correlated with age, gender, HIV status, HIV viral load, CD4 count, stage, and outcomes. Kaplan-Meier curves for overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P < .05 was considered statistically significant). Results.— PD-L1 was positive in 24 of 51 cases (47%) by combined positive score and in 18 of 51 (35%) by tumor proportion score. The median cancer-specific survival and 5-year overall survival were significantly lower in PD-L1+ patients. Age, gender, HIV status, HIV viral load, stage, and cancer progression were not significantly different between the two groups. CD4 count of more than 200/μL was significantly higher in PD-L1+ patients. PD-L1+ status remained statistically significant for worse overall survival on multivariate analysis. Conclusions.— PD-L1+ status is an independent adverse prognostic factor for overall survival in ASCC. This study highlights the potential of PD-L1 targeted therapy in better management of ASCC.

Demographics and incidence of anal squamous cell carcinoma in people living in high HIV prevalence geographical areas

ObjectivesAnal squamous cell carcinoma (ASCC) is an uncommon cancer that is rapidly increasing in incidence. HIV is a risk factor in the development of ASCC, and it is thought that the rapidly increasing incidence in men is related to increasing numbers of people living with HIV (PLWH). We undertook a population-based study comparing the demographics and incidence of ASCC in patients residing high HIV prevalence areas in England to patients living in average HIV prevalence areas in England.MethodsThis is a cross-sectional study following the ‘Strengthening the Reporting of Observational Studies in Epidemiology’ statement. Demographic data and incidence rates of ASCC within Clinical Commissioning Groups (CCGs) between 2013 and 2018 were extracted from the Cancer Outcomes and Services Dataset. CCGs were then stratified by HIV prevalence from data given by Public Health England, and high HIV prevalence geographical areas were compared with average HIV geographical areas.ResultsPatients in high HIV areas were more likely to be young and male with higher levels of social deprivation. Incidence rates in men between 2013 and 2017 were higher in high HIV areas than average HIV areas with a rapidly increasing incidence rates in early-stage disease and a 79.1% reduction in incidence of metastatic stage 4 disease.Whereas women in high HIV areas had lower ASCC incidence than the national average and a low incidence of early-stage disease; however, metastatic disease in women had quintupled in incidence in high HIV areas since 2013.ConclusionsPatients presenting with ASCC in high HIV geographical areas have different demographics to patients presenting in average HIV geographical areas. This may be related to screening programmes for PLWH in high HIV areas.

Molecular and genomic characterisation of a panel of human anal cancer cell lines

Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.

The role of haematological parameters in predicting the response to radical chemoradiotherapy in patients with anal squamous cell cancer

Background Historically, the treatment of choice for anal cancer had been abdominoperineal resection (APR). Radical radiotherapy with concurrent 5-fluorouracil plus mitomycin C chemotherapy was later established as standard therapy, although with a failure rate of 20–30%. The aim of this study was to evaluate the outcomes after radical chemoradiotherapy (CRT), prognostic and predictive factors and patterns of failure. Patients and methods This study included 47 patients treated with radical CRT for patohistologicaly confirmed anal squamous cell carcinoma. Analysed haematological parameters included: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and haemoglobin level. The final logistic regression model included treatment break period. Tumour response was assessed at 24 weeks from CRT completion. Follow-up was performed every 3 months during the first two years, and every 6 months thereafter. Results A complete clinical response (CR) was detected in 30 patients (63.8%). Patients who did not achieve a 6-months CR and those who had a CR after 6 months but then relapsed were referred to surgical treatment. With combined CRT and surgical salvage treatment the CR rate was 80.9%. Patients with CR after 6 months had significantly longer disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). A significant effect on the 6-month response was confirmed for PLR (p = 0.03). Conclusions Important prognostic factors associated with CR were baseline haemoglobin level and period of treatment interruptions. Potential haematological prognostic factors could be PLR and NLR, which can be routinely determined by low-cost and minimally invasive methods.

Reactive Cellular Changes in Anal Cytology Smears and Its Relation to Future Dysplastic Changes in HIV+ Subjects

Introduction/Objective The incidence of anal squamous cell carcinoma is increasing in high risk populations. There is no consensus regarding screening for anal squamous cell carcinoma. Anal pap smears are interpreted using the Bethesda System for cervical cytology. Significant challenges exist for anal cytology that do not apply to cervicovaginal cytology. Methods/Case Report We retrospectively reviewed the anal cytology smears performed in our institution between 2012- 2019. The smears with reactive cytology changes (RCCs) were retrieved, and corresponding follow up smears were reviewed. Results (if a Case Study enter NA) A total of 39 cytology smears with positive RCCs with no dysplasia diagnosis were obtained. All were HIV+. 32 cases were male and 7 females. The overall mean age was: 37.77 + 11.94 SD (range: 23-65 years). The mean age for men was 36.53 + 11.51 and 43.43 + 13.13 for women. Although this mean age was higher for women, the age difference was statistically insignificant (p=0.7, alpha=0.05). Four of the women patients had concomitant cervicovaginal cytology all of which were negative. Only 1 female had a follow up study which was negative. Of the 39 cases, 26 cases (25 men and 1 woman or a total of 66.7%) had followed up smears versus 13 (33.3%) cases with no follow up. A total of 7 out of the 26 follow ups were negative for dysplasia (26.92%). Of the 26 follow ups, a total of 18 (69.23%) were found to have progressed to either ASCUS (15 or 57.69%) or LSIL (3 or 11.53%). One ASCUS was diagnosed as possible high grade. The mean time to convert to dysplasia was 2.06 + 1.25 years (range 1-5 years). Half of the dysplastic cases developed in a 1 year period. Conclusion Patients who have reactive changes on anal cytology should be monitored for possible development of anal neoplasia.