Anal Squamous Cell Cancer Research Articles (Page 1)

Anal squamous cell cancer incidence has risen 2.2% each year over the past decade. Current screening includes anal cytology and high-resolution anoscopy but is burdened with sampling error and patient discomfort. Analyze the T cell microenvironment of normal, premalignant, including low- and high-grade squamous intraepithelial lesions, and cancer. IRB-approved prospective study of patients with anal dysplasia and cancer. Normal, dysplastic and/or cancer tissue are obtained from patients. Tissue is digested to obtain a single cell suspension. Flow cytometry analysis is performed on matched patient samples to evaluate T cell biomarkers. A single tertiary-care academic center. Over the age of 18 and scheduled to undergo high resolution anoscopy, examination under anesthesia, or abdominoperineal resection. Descriptive statistics are utilized to understand differences in the tumor microenvironment of normal, premalignant, and malignant tissue. Twenty patients underwent immunophenotyping. Normal tissue was characterized by the presence of few infiltrating lymphocytes. Anal cancers contained 30-50% regulatory T cells, which were infrequent in dysplasia. In anal cancer, conventional CD4+ T cells expressed high levels of ICOS and PD-1, reflective of tumor antigen recognition. In premalignant lesions, CD4+ conventional T cells also expressed ICOS and PD-1 but lacked coexpression of chronic activation and proliferation markers. CD8+ T cells with a CD103+CD39+ phenotype, indicative of chronic stimulation and tissue residency, were increased in anal cancer. This study is limited by its small sample size. Results may not be generalizable to a larger population. The data demonstrates that T cell infiltrates differ between normal, premalignant, and malignant lesions - with tissue from anal squamous cell cancer containing activated, chronically stimulated T cells. Future clinical diagnostic technology would yield a T cell pathological footprint to differentiate between premalignant and malignant lesions, in addition to the creation of a less invasive serum T cell biomarker test. See Video Abstract.

Conditional overall survival in anal squamous cell cancer: a National Cancer Database analysis.

AimPerineal wound complications are common following salvage surgery in anal cancer. It is not fully known if healing disorders have an impact on oncological outcomes. The aim of this study is to investigate survival in relation to perineal healing status at 3 months after surgery.MethodA retrospective cohort study including all patients with squamous cell anal cancer operated on between January 2005 and June 2020 in Stockholm, Sweden was undertaken. Data collection was by registers and supplemented by chart review. All patients were followed until death or 31 December 2020. Perineal healing status at 3 months was used as a landmark. Association between healing status and recurrence free (RFS) and overall survival (OS) were evaluated using the Cox proportional hazard regression model.ResultsThe final study population comprised 122 patients (78 women). At the landmark date, 73 patients (60%) had a healed perineum and 49 (40%) an unhealed perineum. The R0 resection rate was 92% (112 patients). Follow‐up ranged between 6 and 185 months. Five‐year OS and RFS for all patients was 62% and 56%, respectively. OS was 71% vs. 48% and RFS was 65% vs. 43% for patients with healed versus unhealed wound at the landmark date, respectively. Healing status was significantly associated with OS in univariable analysis (HR 0.52, p = 0.021) and RFS showed a trend (p = 0.054) in the same direction. In a multivariable analysis adjusting for age, gender and T‐stage a statistically significant difference was found concerning OS (HR = 0.47, 95% CI 0.26–0.85) and a trend in the same direction for RFS (HR = 0.60, 95% CI 0.34–1.06).ConclusionThe hypothesis that an unhealed perineal wound following salvage surgery for patients with squamous cell anal carcinoma not only constitutes a surgical but also an oncological problem is strengthened by this study.

e15501 Background: Phase II study have suggested potential benefits of immunotherapy for selected populations based on specific biomarkers in first line therapy. However, there is a clear lack of evidence regarding the efficacy of immunotherapy in subsequent lines of treatment. The objective of this study is to evaluate the benefit of immunotherapy treatment in subsequent lines of therapy for patients with metastatic anal cancer. Methods: Investigators conducted a multicenter, retrospective, observational cohort study involving patients who experienced disease progression after first-line treatment for anal cancer. The study was carried out mainly at the AC Camargo Cancer Center in São Paulo, Brazil, with data collected from January/2007 to June/2024, focusing on patients in subsequent lines of treatment who received either immunotherapy or the phisicyan’s choice chemotherapy. The primary outcomes assessed were Overall Survival (OS) and Progression-Free Survival (PFS). It was considered p value < 0,05 statistically significant. Results: A total of 35 patients were enrolled in the study. Among them, 24 (68.3%) received chemotherapy as their second-line treatment, while 11 (31.4%) were treated with immunotherapy (Pembrolizumab, Nivolumab or Atezolizumab). Of these, six patients (17.1%) were HIV-positive, and 21 (60%) were classified as elderly (over 65 years). Treatment regimens included platinum-based combinations with fluoropyrimidine in 12 patients (34.3%) and taxanes in other 12 patients (34.3%). Median follow-up was 63,5 months (95% CI 54,9 – 72,2). The median overall survival in the immunotherapy group was 30 months (95% CI 12.0 – 47.9), versus 8 months (95% CI 5.2 – 10.7) in the chemotherapy with p value of 0,027. The median progression-free survival for patients receiving second-line treatment was 6.0 months (95% CI 1.6 – 10.3) in the immunotherapy group versus 4.0 months (95% CI 2.1 – 5.8) in the conventional chemotherapy cohort with p value of 0,102. Conclusions: Our findings indicate that immunotherapy significantly improves overall survival in patients with advanced squamous-cell anal cancer who had received one previous line of chemotherapy.

Elective clinical target volume in early squamous cell anal canal cancer: A systematic review and meta-analysis of the risk of recurrence in untreated upper pelvic and external iliac lymph nodes.

ACR Appropriateness Criteria® Staging and Follow-up of Anal Cancer.

Anal cancer is a rare diagnosis, but incidence has been increasing over the past decade. Anal cancer is associated with the human papilloma virus (HPV), specifically the high-risk subtypes of 16 and 18. In addition, the precursor lesion for anal cancer is high-grade squamous intraepithelial lesions (HSILs) and its treatment and surveillance has been emphasized over the last 5 years. The current standard of care for anal cancer includes the Nigro protocol, concurrent chemoradiation, typically radiation with systemic mitomycin and 5-fluorouracil (5-FU). The protocol's efficacy laid the foundation for sphincter preservation and non-operative management. This review will detail the essential clinical trials in the treatment and surveillance of premalignant lesions and anal squamous cell cancer, including alterations in radiation dosing, systemic chemotherapy, and immunotherapy over the last several decades.

Is the omission of the external iliac or upper pelvic lymph nodes from elective irradiation safe in selected anal canal squamous cell cancers?

Co-infection with human immunodeficiency virus (HIV) significantly increases the incidence of human papillomavirus (HPV) infection and HPV-related cancers among men who have sex with men (MSM). Conversely, HPV infection can also influence HIV acquisition rates. HIV-induced immune suppression may affect chromosomal stability, gene expression, protein function and other molecular components in MSM with HPV-related cancers. Additionally, HIV infection also alters cellular mechanisms by compromising immune responses and epithelial integrity. In this review, we reviewed the influence of HIV on specific HPV-related cancers in MSM, including oropharyngeal squamous cell carcinoma, penile cancer, and anal cancer. We integrated epidemiological data from the past five years and discussed diagnosis and treatment strategies. Overall, our review offers crucial insights into the underlying molecular and cellular mechanisms of these co-infection MSM patients. Our review aims to assist future research in developing effective treatment strategies for MSM with HIV/HPV co-infection.

Aim was to compare the efficacy of interventional radiotherapy (IRT) boost vs. external beam radiotherapy (EBRT) boost after chemoradiation (CCRT) in patients with anal cancer (AC). The P.I.C.O. framework was: in patients with AC [P], is IRT boost [I] superior to EBRT boost [C] in terms of local control (LC), cancer specific survival (CSS), overall survival (OS), distant meta-static free Survival (DMFS), colostomy free survival (CFS) and toxicity [O]? 651 patients were analyzed. The median 5-year locoregional control rates was 87.8% in the IRT boost group versus 72.8% in the EBRT boost group. The 5-year cancer-specific survival rate was 91% in the IRT boost group versus 78% in the EBRT boost group. 5-years overall survival was 74.6% in IRT boost versus 67.7% in the EBRT boost. 5-years disease metastasis-free survival rate was 92.9% in IRT boost group vs. 85.6% for the EBRT boost group. Cancer-free survival rate was 76.8% in the IRT group vs. 63.1% in the EBRT boost group. Acute toxicity above grade 2 was less common in the IRT boost group while chronic toxicity was similar between both groups. IRT boost after CCRT could lead to better outcomes than EBRT boost in treating AC.

This study aimed to determine the prognostic significance of length of tumour (mrT stage) and depth of extramural spread (mrEMS) in anal squamous cell cancer(SCC) treated by chemoradiation with curative intent. Locally advanced anal SCC (T3-4 N+) have poorer prognosis, but it is unknown whether the lateral spread of the tumour (extramural spread beyond the bowel wall) also confers poor prognosis in anal SCC, as it does for rectal cancer. T stage and mrEMS can be readily assessed by pelvic magnetic resonance imaging (MRI) routinely undertaken to stage anal SCC. 125 patients were included. Baseline mrT, mrN and mrEMS were assessed with response to chemoradiation and outcomes. Receiver operating curve (ROC) curve was used to determine a binary cut-off for mrEMS according to 3-year progression- free survival (PFS). 43% were mrT3-4 and 38% were mrEMSpoor at baseline. 87% achieved mrCR. 3-year PFS and overall survival (OS) were 70.6% and 82%. On univariate analysis worse 3-year PFS was seen for mrT3-4 (HR 3.105), mrEMSpoor (HR 4.924) and failure to achieve mrCR (HR 20.591). By univariate analysis, worse 3-year OS was seen for mrT3-4 (HR 4.134), mrEMSpoor (HR 10.251) and failure to achieve mrCR (HR 19.289). On multivariate analysis, only mrEMSpoor and failure to achieve mrCR remained prognostic. mrN was not prognostic. MrEMSpoor is a simple prognostic imaging biomarker for poorer survival which can be readily assessed by radiologists on routine imaging. mrEMS should be considered as a future stratification variable to identify high-risk SCC and consider escalation of treatment and surveillance strategies.

We sought to assess the effectiveness and harms of initial treatment strategies for stage I through III anal squamous cell anal cancer. We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between January 1, 2000, and March 2024, for randomized controlled trials and nonrandomized studies of interventions comparing initial treatment strategies. Individual study risk of bias and overall strength of evidence were evaluated for a prespecified outcome list using standardized methods. We identified 33 eligible studies and extracted data. Six were deemed low to moderate risk of bias. Compared with radiation therapy alone, chemoradiation therapy (CRT) with 5-fluorouracil (5-FU) and mitomycin C probably shows a benefit in locoregional failure, disease-specific survival, and colostomy-free survival (moderate strength of evidence) yet may result in greater overall and acute hematological toxicity, with no difference in late harms (low strength of evidence). CRT with 5-FU plus mitomycin C may show a benefit in locoregional failure, disease-specific survival, and colostomy-free survival rates compared with 5-FU alone (low strength of evidence). CRT with 5-FU plus cisplatin vs 5-FU plus mitomycin C probably results in no differences in several effectiveness outcomes or overall acute or late harms and probably increases hematological toxicity with mitomycin C (moderate strength of evidence). Compared with CRT using capecitabine plus mitomycin C, CRT with capecitabine plus mitomycin C and paclitaxel may improve overall survival, disease-specific survival, and colostomy-free survival yet cause more acute harms (low strength of evidence). Evidence was insufficient for remaining comparisons. CRT with 5-FU plus mitomycin C or 5-FU plus cisplatin is likely more effective yet incurs greater acute hematological toxicity than radiation therapy alone or single-agent CRT. Adding paclitaxel to capecitabine plus mitomycin C may increase treatment efficacy and toxicity. Evidence is insufficient comparing posttreatment surveillance strategies and patient-reported outcomes, highlighting research opportunities.

Anal squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has shown high success rates, yet challenges such as treatment resistance and recurrence persist. The present study aimed to investigate the associations between immunohistochemical (IHC) evaluation, treatment response and prognosis in anal SCC. A retrospective cohort analysis included 42 patients with anal SCC treated at a single institution between 2006 and 2022. Human papillomavirus (HPV) status was determined, and the IHC analysis of p16, p53 and PD-L1 expression was conducted using formalin-fixed, paraffin-embedded biopsies. A complete response to RT/CRT was observed in 71.4% of patients. Recurrence occurred in 38.1% of cases, of which 7.1% had local-regional recurrence (LRR), 14.3% had distant recurrence (DR), and 16.7% had both LRR and DR. HPV positivity (71.4%) was significantly associated with p16 positivity. Lack of complete response was associated with HPV-negative status, p16-negative status, increased recurrence and DR. In addition, recurrence was significantly associated with p53-positive status, and p53 positivity was significantly associated with increased LRR. PD-L1 positivity, defined as a combined positive score (CPS) ≥1% was found in 73.8% of the patients, and exhibited significant associations with HPV positivity and p16 positivity. PD-L1 CPS ≥ 1% was also associated with an increased LRR. Univariate analysis revealed that age <65 years, a complete response and HPV positivity were associated with increased 5-year overall survival (OS), while a complete response, HPV positivity and p53-negative status were associated with increased 5-year disease-free survival (DFS). Multivariate analysis identified that age <65 years and HPV positivity are independent prognostic factors for 5-year OS, and a complete response and p53-negative status are independent prognostic factors for 5-year DFS. In conclusion, these findings suggust that the identification of HPV status and poor prognostic biomarkers at diagnosis may be used to guide personalized treatment strategies, with the combination of immunotherapy with standard CRT potentially providing improved outcomes.

Efficacy and Toxicity of (Chemo)Radiation Therapy in HIV+ Patients with Squamous Cell Anal Cancer, a Subgroup Analysis of the National Multicenter Cohort FFCD-ANABASE

Solid organ transplant recipients are at an increased risk for anogenital Human Papillomavirus (HPV)-related disease, including anal high-grade squamous intraepithelial lesions (HSIL) and anal squamous cell cancer (ASCC). Guidelines for ASCC screening in transplant recipients are limited. Our aim was to understand current practice of ASCC screening in adult liver transplant (LT) candidates and recipients at transplant centers across the United States. We surveyed medical directors of 113 LT centers across the United States which had publicly available contact information. The survey evaluated center perceptions on cancer and HPV disease risk in transplant populations, ASCC screening, barriers and facilitators for ASCC screening and HPV vaccination practices. We received 26/113 (23%) responses, of which 24 were complete and included in the analysis. Eleven of 24 (46%) centers reported screening for ASCC and 3/24 (12.5%) centers reported having formal guidelines. Centers who perform ASCC screening were more likely to perform transplants in people living with HIV and were more aware of the burden of HPV disease in transplant populations. All respondents believed that additional data on the impact of screening on ASCC incidence would support screening decisions. Increased access to specialists for screening/high-resolution anoscopy was also perceived as a facilitator. Only 7/24 (29%) centers regularly evaluated HPV vaccination status of their patients. This national survey of LT centers reveals non-standardized ASCC screening practices, and identified data, educational and resource needs to improve prevention of ASCC in this population.

Background Anal Pap smears are imperative to screening for human papillomavirus (HPV)-associated anal squamous cell cancers, particularly in patients living withhuman immunodeficiency virus (HIV) given a higher incidence of disease. Self-collection of specimens may be favored by patients and more feasible to collect, increasing screening. Methods This was a single-center observational cohort study at a single academic medical center Infectious Diseases clinic from October to December 2021. We aimed to improve compliance of anal Pap collection documentation of "self-collected" versus "physician-collected" as well as verify if self-collected specimens (SCS) were adequate for interpretation equivalent to physician-collected specimens (PCS). Additionally, we aimed to evaluate patient and provider satisfaction with self-collected anal Paps. Results Sixty anal Pap smears were available for evaluation. The rate of documentation of the collection method (self-collected vs. physician-collected) was 88% during the intervention. A total of 75% of patients opted for self-collection, and 35/45 (78%) of these samples were adequate for interpretation. There was no difference in the adequacy of specimen (the ability of a cytopathologist to interpret the specimen) between the SCS and PCS. Conclusion Limited prior data suggest self-collected anal Pap specimens are adequate for interpretation only slightly less often than PCS. In our small cohort, there was no statistically significant difference between collection methods. Satisfaction with self-collection of specimens was high for both patients and providers. Additional validation in more diverse/larger clinical settings may be helpful to support this practice.

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan-Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11-47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5-66.5%), 54.5% (95% CI 44.4-66.8%), and 26.8% (95% CI 18.6-38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16-46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99-42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05-6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

Anal squamous cell cancer (ASCC) in early stages (T1-2N0M0) is treated with chemoradiotherapy with a 3-year overall survival (OS) exceeding 90%. In Swedish guidelines, it has been optional to include the external iliac and presacral lymph node (LN) stations in radiotherapy (RT) treatment fields in early ASCC. Two Swedish hospitals treating ASCC (SU: Sahlgrenska University Hospital; UU: Uppsala University Hospital) have chosen different approaches since 2010. This study included consecutive patients with early ASCC (T1-2N0M0) treated between 2010 and 2017 at both sites (SU n = 70; UU n = 46). Data were retrieved from medical records and RT charts. At SU, the external iliac and presacral LN stations were included in elective LN irradiation in 96.8% (n = 60) and 95.2% (n = 59) patients compared to 2.4% (n = 1) and 29.3% (n = 12) at UU. The mean elective LN volume was 2,313 cc (interquartile range [IQR] 1,951-2,627) in the SU cohort compared to 1,317 cc (IQR 1,192-1,528) in the UU cohort, p < 0.0001. No case of regional LN recurrence was seen in either cohort. Disease specific survival (DSS) at 5 years was 95.7% (confidence interval [CI] 90.1-100.0) in the SU cohort and 97.8% (CI 93.2-100.0) in the UU cohort (p 0.55). OS at 5 years was 84.5% (CI 76.1-93.0) in the SU cohort and 82.6% (CI 69.6-89.1) in the UU cohort (p 0.8). We found no differences in regional recurrence, DSS or OS between the cohorts treated with different elective LN volumes. In this population-based study, reduction of RT volume in early ASCC did not lead to inferior outcome.

Abstract Background Fistula cancer is a rare and often devastating diagnosis in patients with perianal fistulising Crohn’s disease (CD). Fistula cancer management is a complex process requiring multi-disciplinary effort. However, given the low incidence and subsequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of fistula cancer. To inform clinical practice, we developed consensus guidelines on fistula cancer in perianal fistulising Crohn’s disease by multidisciplinary experts from the international TOpCLASS consortium. Methods We performed a systematic review of the literature by standard methodology, using the Newcastle-Ottawa quality assessment tool. Data were retrieved from articles according to these domains: epidemiology and risk factors, clinical presentation, diagnostics, staging, and treatment. We developed consensus statements using a Delphi consensus approach. Participants included gastroenterologists, surgeons, radiologists, and pathologists. We performed two rounds of voting: (1) online survey followed by statement edits and (2) hybrid meeting with discussion until over 80% consensus was achieved for each statement. Results Of 550 articles identified, 99 were eligible, and 80 articles were included. The overall quality of evidence was low. Seven statements were accepted in the final consensus (Table 1). Patients with longstanding (&amp;gt;10 years) perianal fistulising CD should be considered at small but increased risk of developing fistula cancer, including anal squamous cell cancer (SCC) and anorectal carcinoma. Risk factors for anal SCC, including human papilloma virus (HPV), should be considered. Clinical signs and symptoms of fistula cancers are non-specific, and several case reports included asymptomatic patients. New or refractory/progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Regarding diagnostics, multiple modalities may be required, including repeated exam under anesthesia with biopsy. Multidisciplinary team efforts were deemed central for the management of fistula cancers. Conclusion Clinicians managing patients with perianal fistulising CD should be aware of the risk of fistula cancers, including anal SCC and anorectal carcinoma. Our expert consensus recommends consideration of patient factors including duration of fistulas, HPV status, and perianal symptoms, and gives guidance on diagnostic modalities and treatment considerations. Multidisciplinary coordination of care is paramount, and more studies in the field are needed.

The current standard for anal cancer treatment is essentially a 'one size fits all' approach where the dose of radiotherapy is similar whether the tumor is very small or very large. Trials are ongoing to evaluate dose de-escalation or escalation in localized disease depending on tumor size. The aim of the study was to assess results of a personalized approach involving dose stratification by stage and boost dose adjusted according to tumor early response. We retrospectively reviewed squamous cell anal cancer (SCAC) patients treated between 2011 and 2021 by long-course intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy (CT); a sequential boost could be administered by IMRT or interventional radiotherapy (IRT) to obtain a total equivalent dose in 2 Gy (EQD2) of 54-60 Gy. We analyzed 110 patients (61% T3-4 stage, 71% node-positive). A total of 68.2% of patients received a sequential boost, mainly by IRT; median total EQD2 to primary site was 59.3 Gy. Acute ≥G3 toxicity rate was 36.4%. Median follow-up (FUP) was 35.4 months. A total of 83% of patients achieved clinical complete response (cCR); locoregional recurrence (LRR) occurred in 20.9% and distant metastases in 6.4% of cases. A total of 12.7% patients underwent salvage surgery. A total of 25.5% of patients reported ≥G2 and 4.5% ≥G3 late toxicity. The estimated 3-year overall survival, disease-free survival and colostomy-free survival were 92%, 72% and 84% respectively; 3-year-LRR was 22%. Nodal stage was associated with poorer cCR probability and higher LRR (p<0.05). Our results on a large cohort of patients with locally advanced SCAC and long FUP time confirmed the efficacy of IMRT; high local control and manageable toxicity also suggest IRT as a promising method in treatment personalization.