Anal Squamous Cell Cancer Research Articles

Anal human papillomavirus and anal squamous cell cancer in people living with HIV/AIDS: implications for southern africa

Southern Africa has the largest burden of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in the world. Highly active antiretroviral therapy (HAART) is increasingly being made available in the region. The disease has shifted from being a death sentence to that of a chronic disorder with the availability of HAART. The morbidity and mortality in people living with HIV/AIDS (PLWHA) in the developed world seems to be shifting from that of opportunistic infection to malignancy, particularly non-AIDS-defining cancer. A similar trend may be imminent in the developing world owing to the availability of HAART. Squamous cell cancer of the anus is a cancer with a seemingly increasing incidence in PLWHA. This review explores the possible impact that a rise in the incidence of squamous cell cancer of the anus would have on the region, and strategies that may be employed to identify and counteract this escalation.

The Effect of the UK Coordinating Centre for Cancer Research Anal Cancer Trial (ACT1) on Population-based Treatment and Survival for Squamous Cell Cancer of the Anus

Between 1987 and 1994, three randomised phase III trials showed that chemoradiotherapy with mitomycin C and 5-fluorouracil was superior to radiotherapy alone (ACT1, European Organization for Research and Treatment of Cancer) or radiotherapy with 5-fluorouracil (Radiation Therapy Oncology Group 87-04, Eastern Cooperative Oncology Group 1289) for squamous cell carcinoma of the anus. We explored the population-based changes in England before, during and after the UK-based ACT1 trial. Information was extracted from the National Cancer Data Repository on patients diagnosed with squamous cell anal cancer in England between 1981 and 2010 (n = 11 743). Robust treatment information was available for the Yorkshire region (n = 1065). Changes in treatment patterns and 3 year survival were investigated in 7 year cohorts before, during and after the ACT1 trial. In Yorkshire, the proportion of patients receiving surgery alone fell from 61.6% before, 29.8% during and 12.5% after ACT1; the proportion of patients receiving primary chemoradiotherapy rose from 6.5% before, 17.7% during and 58.8% after ACT1 and continued to rise to 70.3% in the subsequent period. Three year survival improved during the study period from 59.5% (95% confidence interval 56.6–62.2) before ACT1 to 73.6% (95% confidence interval 71.9–75.2) after the trial. Survival in Yorkshire was comparable with that in England. The treatment for squamous cell carcinoma of the anus changed dramatically during the study period. The predominant use of surgery before ACT1, a transition phase during the trial and a dramatic increase in the use of chemoradiotherapy after ACT1 provide strong evidence of the effect of the trial on population-based practice. Survival continued to increase during this period.

PTU-192 Management of anal intraepithelial neoplasia (AIN): a multicentre audit

Introduction Anal intraepithelial neoplasia (AIN) although rare is a precursor to anal squamous cell cancer (SCC). There is little evidence on the effectiveness of follow-up protocols. This audit aimed to assess the compliance with follow-up guidelines from The Association of Coloproctology of Great Britain and Ireland (ACPGBI). Method A retrospective multicentre audit was performed, all patients with histologically confirmed AIN from 1 Jan 2008 were identified from the cancer network pathology database with a centralised anal MDT. Assessment, follow-up, and outcomes were obtained from the hospitals clinical results reporting system and compared to the ACPGBI published guidelines on AIN. Results There were a total of 24 patients, 37.5% male (n = 9), with AIN. Mean age 58 (range 20–94). Mean follow-up time 24 months (range 2–65). 16.6% had AIN1 (n = 4), 16.6% had AIN2 (n = 4), 66.6% had AIN3 (n = 16). Of the patients diagnosed with AIN3, 75% (n = 14) were discussed at anal MDT, 100% (n = 16) had guideline compliant follow-up. Of the 8 patients with AIN1 or AIN2, 62.5% (n = 5) had at least 6 monthly follow-up, 43.7% (n = 7) of patients with AIN3 had a re-biopsy of the site of lesion. 1 (6.5%) patient with AIN3 progressed within 1 year to squamous cell carcinoma. 75% of female patients with AIN were managed with a gynaecologist. Conclusion This study showed that, once diagnosed with AIN, there is good compliance with guideline focused follow-up, and the majority of patients are discussed in a centralised anal MDT. Progression to anal cancer was in keeping with that seen in other studies. Disclosure of interest None Declared.

Considering Standards of Care for Anal Cancer.

High-resolution anoscopy (HRA) has become a term that induces fear and trepidation in thehearts ofmost colorectal surgeons. There is a certain sinking feeling when one considers thetimeandeffort thatwillbe expended, with little return, when the standardof carebecomes the routineuseofHRA for all human immunodeficiencyvirus–positivepatients. This timeandeffortare fora0.131%riskofanalcancer in thehighestrisk group—men having sex with men who have human immunodeficiency virus. In fact, colorectal surgeons observe most of these individuals ona regular basis in theoffice if they have condylomaor symptomsof anal disease.Anoscopywithouthighresolutionactually revealsmostanal lesions thatcause symptoms. The time spent performing HRA compared with routine anoscopy may discourage most health care professionals from using HRA, except those focused on high-grade squamous intraepithelial lesions (HSIL) andhuman immunodeficiency as a specialty. The study reported byHicks et al1 in this issue emphasizes some of the controversies surrounding the overall problem of HSIL.Asusual, therearemorequestions thananswers.Can the authors tell us how many patients without symptoms, never havingHRA but observed closely, will develop anal squamous cell cancer? Is there a reliable correlation between the presence of an anal lesion and anal pain andHSIL? Can routine follow-upwith anoscopy and destruction of obvious anal lesions have the same protective effect as HRA on anal cancer? Can asymptomatic high-risk individuals beobserveduntil theydeveloponeof the symptomsassociatedwithHSIL?What are the “findings consistent with dysplasia,” as mentioned by the authors?Only 29%of thepatients referredhad cytologic findings onanalPapanicolaou tests showinghigh-gradedysplasia.How helpful is the Papanicolaou test, if the test andHRAwere consistent in only 66% of cases? Finally, if only 30% of the group referredbyprimarycarephysiciansfor risingconcernaboutanal cancer hadHSIL and none had anal cancer, why not start with follow-up routine regular anoscopy instead of HRA?

Chemoradiotherapy of squamous cell anal cancer

Squamous cell carcinoma of the anal canal is a rare disease and is no more than 1.7-2% of the annual cancer incidence. Chemoradiation therapy - the standard modern treatment of squamous cell anal cancer. Short-term recurrence-free period of the new approaches to the treatment of anal cancer, in particular to the new regimes chemoradiotherapy.

Long Survival (Cure) to Cisplatin/Infusional 5-Flurouracil in Metastatic Squamous Cell Anal Cancer with Extensive Liver and Lung Metastases

Background: Metastatic anal Squamous Cell Carcinoma (SCC) is a relatively uncommon malignancy that is usually treated with palliative platinum based chemotherapy. Response rates are modest and complete responses are rare. Case Report: Here we report on a case of advanced SCC with the extensive visceral metastatic disease that has possibly been cured with chemotherapy alone. The patient has received 6 cycles of Cisplatin and 5FU and has remained in complete remission for over 7 years. Conclusion: This is the first report of a case of metastatic anal SCC that has been cured with chemotherapy and highlights the need to remain optimistic when treating patients with “palliative” chemotherapy.

Anal human papillomavirus (HPV) prevalences and factors associated with abnormal anal cytology in HIV-infected women in an urban cohort from Rio de Janeiro, Brazil.

Identifying factors, including human papillomavirus (HPV) genotypes, associated with abnormal anal cytology in HIV-infected women have implications for anal squamous cell cancer (SCC) prevention in HIV-infected women. Anal and cervical samples were collected for cytology, and tested for high-(HR-HPV) and low-risk HPV (LR-HPV) genotypes in a cross-sectional analysis of the IPEC Women's HIV Cohort (Rio de Janeiro, Brazil). Multivariate log-binomial regression models estimated prevalence ratios for factors associated with abnormal anal cytology [≥ atypical squamous cells of undetermined significance, (ASC-US)]. Characteristics of the 863 participants included: median age 42 years, 57% non-white, 79% current CD4+ T-cell count >350 cells/mm(3), 53% HIV-1 viral load <50 copies/mL, median ART duration 5.8 years. Fifty-one percent of anal specimens contained ≥ 1 HR-HPV genotype; 31% had abnormal anal cytology [14% ASC-US, 11% low-grade squamous intra-epithelial lesion, (LSIL); 2% atypical squamous cells-cannot exclude high-grade SIL (ASC-H); 4% high-grade SIL/cancer (HSIL+)]. In multivariate analysis, cervical LSIL+, nadir CD4+ T-cell count ≤ 50 cells/mm(3), HIV-1 viral load ≥ 50 copies/mL, and anal HPV 6, 11, 16, 18, 33, 45, 52, 56, and 58 were associated with ≥ anal ASC-US (p<0.05). Abnormal anal cytology and HR-HPV prevalences were high. HIV-infected women with cervical LSIL+, low nadir CD4+ counts, or detectable HIV-1 viral loads should be a particular focus for enhanced anal SCC screening efforts.

254. A novel chemoradiotherapy regimen for squamous-cell anal cancer

The aim of this trial was to investigate safety and efficacy of anal cancer chemoradiotherapy with cisplatin, bleomycin and local hyperthermia.

Smaller pelvic volume is associated with postoperative infection after pelvic salvage surgery for recurrent malignancy

BackgroundPatients with recurrent pelvic malignancy have few treatment options, and surgery is fraught with complications. We sought to characterize the relationship between radiographic pelvic volume and postoperative complications after pelvic salvage surgery. MethodsA retrospective chart review of all patients undergoing pelvic exenteration or abdominoperineal resection for recurrent malignancy between 1998 and 2013 was performed. Preoperative computed tomography was used to determine pelvic volume. ResultsForty-two patients underwent surgery for recurrent rectal (26, 62%), prostate (8, 19%), or anal squamous cell cancer (8, 19%). Thirty-eight patients (90%) suffered complications and there was one (2%) perioperative death. Decreasing pelvic volume was associated with deep or organ space infections (P = .01), sepsis (P = .03), and fistula (P = .05) on univariate analysis. Infections remained significant on multivariate analysis (odds ratio, 1.01; P = .02). ConclusionsPelvic salvage surgery for recurrent malignancy is associated with a high complication rate yet low mortality. Decreasing pelvic volume is associated with increasing risk of deep or organ space infections.

Clinical experience of SIB-IMRT in anal cancer and selective literature review.

PurposeTo evaluate feasibility and outcome of our institutional SIB-IMRT schedule in patients with anal cancer and to selectively review the literature on different SIB-IMRT schedules.Patients and methodsBetween 01/08-06/13 25 patients with biopsy proven squamous cell anal cancer were treated in our institution with IMRT. Radiotherapy was delivered in two series using a SIB-IMRT schedule of 45 Gy/1.8 Gy to the primary tumor and adjacent pelvic lymph nodes and 38 Gy/1.52 Gy to elective nodes followed by an IMRT boost of 7×2 Gy = 14 Gy to the primary tumor and involved nodes (cumulative prescription dose: 59 Gy).ResultsMean follow-up was 20 months (range: 4-68). The 2-year-local control, colostomy-free survival, distant metastases-free survival and overall survival rates were 92%, 92%, 92%, and 88%, respectively. Grade 3 acute skin toxicity was observed in 6 patients (24%). No high grade gastrointestinal or urinary acute toxicity occurred. Four patients required more than one day of treatment interruption due to acute toxicity. No grade 3 or higher late sequelae were observed.ConclusionWe present our institutional SIB-IMRT experience treating patients with anal cancer in two series using moderate single doses from 1.5-2.0 Gy. Our results, in terms of loco-regional outcome and toxicity, were comparable to other studies. The incidence of treatment interruptions was very low. Therefore this schedule appears to be safe for clinical use.

740P - Prognostic Factors for Local Recurrence, Distant Metastases and Survival in Anal Carcinoma

ABSTRACT Aim: Recent literature has sought prognostic factors for survival outcomes in anal cancer patients. Similarly, our study aims to determine prognostic factors for local disease recurrence, distant metastases and survival from patients treated with standardized radical chemo-radiotherapy at the Rosemere Cancer Centre, Lancashire, UK. Methods: Patients treated with radical concurrent chemoradiation for non-metastatic squamous cell anal cancer from September 2000 to January 2013 were retrospectively studied. Kaplan-Meier and Cox Regression proportional hazards methods were used to assess prognostic value of age, sex, tumour size, anal canal circumference involved (ACCI), nodal disease, tumour location and pre-treatment haemoglobin. Results: A total of 148 patients (95 females, 53 males) with a mean age of 63 were studied. From the sample population 15% of patients suffered local disease recurrence and 10% developed distant metastases. The estimated five-year overall survival and cancer specific survival was 84% and 86% respectively. Predictors of local recurrence were tumour size greater than 5cm and over two-thirds ACCI (p Conclusions: Tumour size, nodal disease, over two thirds ACCI and low pre-treatment haemoglobin confer poorer prognostic and survival outcomes. Future use of intensity modulated radiation therapy (IMRT) can decrease patient morbidity, which may allow increase of radiation doses for locally advanced anal cancers and thus improve local control and survival outcomes. Disclosure: All authors have declared no conflicts of interest.

HPV and anal cancer in HIV-infected individuals: a review.

HIV infection is one of the strongest risk factors for anal squamous cell cancer (ASCC). Most ASCC are caused by HPV, and most HPV-associated ASCC are caused by HPV-16. Anal HPV infections are very common in men who have sex with men (MSM), and nearly universal among HIV-infected MSM. High-grade anal intraepithelial neoplasia (HGAIN), the precursor for ASCC, is present in about 30 % of HIV+ MSM, but neither the progression rate to ASCC nor the regression rate are known. The incidence rate of ASCC among HIV-infected people has risen in the first decade after cART became available, but appears to be plateauing recently. Anal cytology has poor sensitivity and specificity. High resolution anoscopy (HRA) is advocated by some as a screening tool in high-risk groups, but is cumbersome and time-consuming and it is unknown whether HRA followed by treatment of HGAIN prevents ASCC. More research is needed on progression and regression rates of HGAIN, on effective therapy of HGAIN, and on biomarkers that predict HGAIN or anal cancer. HPV vaccination and earlier start of cART may prevent most anal cancers in the long run.

Prognostic factors for squamous cell anal canal cancer.

e15000 Background: Tumour size, nodal involvement and sex are recognized prognostic factors in squamous cell anal cancer. Our study aims to evaluate survival and potential prognostic factors amongs...

Anal Squamous Cell Cancer in African Americans With and Without HIV: A Comparative Study

1.1 Background: The incidence of anal carcinoma has increased over the last few decades especially in African Americans (AA) despite the use of highly active anti-retroviral therapy (HAART). Here, we retrospectively review oncologic outcomes of AA patients with anal squamous cell carcinoma (SCC) with and without HIV to further examine the cause of this trend. Materials and Methods: All adult AA patients diagnosed with anal SCC from 2000 to 2007 who met inclusion were examined. All patients were staged according to the American Joint Committee on Carcinoma (AJCC) sixth edition staging classification. Patients were divided into two cohorts: HIV (-) and HIV (+). Demographics, comorbidities, and oncologic outcomes were analyzed. Results: Twenty-two AA patients with anal SCC were analyzed. Fifteen (68.%) were HIV (+) and seven (32%) were negative. Seventy-four percent of HIV (+) patients were on HAART therapy at the time of diagnosis. The HIV (+) cohort was significantly younger, mostly male, and had more comorbidities compared to the negative cohort. There was no difference in tumor, nodal or metastasis (TNM) stage for both cohorts. HIV (+) patients were more likely to receive non-operative therapy. The 5-year survival rate for HIV negative and positive patients was 57% and 58%, respectively. AJCC stage was the only factor predictive of survival after performing Cox hazard proportional regression analysis, HR: 1.96 (95% CI, 0.987 to 3.881). Conclusions: In the HAART era, HIV (+) AA patients are at high risk of developing anal SCC. However, the prognosis of HIV (+) AA with anal SSC is similar to that of their HIV (-) counterparts. Carcinoma stage is the only factor predictive of survival.

Anal Invasive Squamous Cell Cancer and Human Papillomavirus Distribution in HIV-Infected and Non-HIV-Infected Individuals

Invasive-squamous-cell-cancer (ISCC) of the anal canal is an uncommon disease. Human papillomavirus (HPV) is the etiological agent of most of types of ISCC. The incidence of ISCC has been increasing in HIV-infected individuals, even after the introduction of highly active antiretroviral therapy. The aim of this study was to analyze biopsy specimens from patients diagnosed with ISCC at a tertiary hospital from 1983 to 2012 in order to detect HPV-DNA. Methods: Formaldehyde-fixed, paraffin-embedded specimens from patients with ISCC underwent HPV-DNA genotyping using multiplex PCR assay. Results: A total of 31 cases were collected; 10 were HIV-infected (9 men, 1 woman) and 21 non-HIV-infected (11 men, 10 women). HPV infection was detected in 87.5% (7/8) of the HIV-infected patients (DNA from 2 biopsies was degraded) and 76.2% (16/21) of non-HIV-infected individuals. Multiple-type infections were only found in 28.6% (2/7) of the HIV-infected patients (no multiple-type infections in non-HIV-infected individuals). The most prevalent type was HPV-16: 50% (4/8) in the HIV-infected group (57% [4/7] of the HPV-positive samples) and 66.7% (14/21) in the non-HIV-infected group (87.5% (14/16) of the HPV-positive samples). Remarkably, 37.5% (3/8) of the HIV-infected group had high-risk HPV types not included in the vaccines (HPV-33, 51, 52, and 66) compared with 4.8% in the non-HIV-infected group (1/21, HPV-52). All cases of anal ISCC in HIV-infected patients were recorded in the highly active antiretroviral therapy era. Conclusion: HIV-infected patients presented anal ISCC with a higher proportion of high-risk HPV types not covered by the conventional vaccines than non-HIV-infected individuals.

EGFR, KRAS, BRAF, and PIK3CA characterization in squamous cell anal cancer.

Combined chemoradiation therapy is the gold standard in the treatment of squamous cell anal cancer (SCAC). However, even if the response rate is very high, many patients eventually relapse or experience a reccurrence, thus requiring an invasive surgical procedure that has severe side effects. Most SCAC tumors overexpress epidermal growth factor receptor (EGFR); therefore, it is reasonable to consider anti-EGFR drugs as a new treatment option, as demonstrated by anecdotal reports. Promising results obtained in other solid tumors, both squamous and non-squamous, have revealed that an increase in the EGFR gene copy number may predict the efficacy of anti-EGFR therapies, while the presence of mutations in downstream members of the EGFR pathway may confer resistance. These markers have been only sporadically considered in SCAC. We investigated the status of the EGFR gene using FISH and examined KRAS, BRAF, and PIK3CA hot-spots mutations using sequencing analysis in a cohort of 84 patients affected by SCAC. Twenty-eight patients (34%) showed an increase in EGFR gene copy number due to amplification (4%) or to polysomy (30%). KRAS and PIK3CA gene mutations were found in 4 (5%) and 13 patients (16%), respectively. No mutations were found in the BRAF gene. The characterization of the EGFR pathway may help in identifying different subgroups of SCAC that have specific molecular features, which may have implications in what targeted therapies are used to treat each patient.

Inhibition of mTOR reduces anal carcinogenesis in transgenic mouse model.

The molecular mechanism of human anal squamous cell carcinoma (ASCC) is unclear, and the accumulating evidence indicate association of ASCC with the activation of the Akt/mTOR pathway. Here we describe a mouse model with spontaneous anal squamous cell cancer, wherein a combined deletion of Tgfbr1 and Pten in stratified squamous epithelia was induced using inducible K14-Cre. Histopathologic analyses confirmed that 33.3% of the mice showed increased susceptibility to ASCC and precancerous lesions. Biomarker analyses demonstrated that the activation of the Akt pathway in ASCC of the Tgfbr1 and Pten double knockout (2cKO) mouse was similar to that observed in human anal cancer. Chemopreventive experiments using mTOR inhibitor-rapamycin treatment significantly delayed the onset of the ASCC tumors and reduced the tumor burden in 2cKO mice by decreasing the phosphorylation of Akt and S6. This is the first conditional knockout mouse model used for investigating the contributions of viral and cellular factors in anal carcinogenesis without carcinogen-mediated induction, and it would provide a platform for assessing new therapeutic modalities for treating and/or preventing this type of cancer.

Progression of anal high‐grade squamous intraepithelial lesions to invasive anal cancer among HIV‐infected men who have sex with men

The incidence of anal cancer is elevated in human immunodeficiency virus (HIV)-infected men-who-have-sex-with-men (MSM) compared to the general population. Anal high-grade squamous intraepithelial lesions (HSIL) are common in HIV-infected MSM and the presumed precursors to anal squamous cell cancer; however, direct progression of HSIL to anal cancer has not been previously demonstrated. The medical records were reviewed of 138 HIV-infected MSM followed up at the University of California, San Francisco, who developed anal canal or perianal squamous cancer between 1997 and 2011. Men were followed up regularly with digital anorectal examination (DARE), high-resolution anoscopy (HRA) and HRA-guided biopsy. Although treatment for HSIL and follow-up were recommended, not all were treated and some were lost to follow-up. Prevalent cancer was found in 66 men. Seventy-two HIV-infected MSM developed anal cancer while under observation. In 27 men, anal cancer developed at a previously biopsied site of HSIL. An additional 45 men were not analyzed in this analysis due to inadequate documentation of HSIL in relation to cancer location. Of the 27 men with documented progression to cancer at the site of biopsy-proven HSIL, 20 men progressed from prevalent HSIL identified when first examined and seven men from incident HSIL. Prevalent HSIL progressed to cancer over an average of 57 months compared to 64 months for incident HSIL. Most men were asymptomatic, and cancers were detected by DARE. Anal HSIL has clear potential to progress to anal cancer in HIV-infected MSM. Early diagnosis is facilitated by careful follow-up. Carefully controlled studies evaluating efficacy of screening for and treatment of HSIL to prevent anal cancer are needed.

Anal intraepithelial neoplasia and squamous cell carcinoma in HIV‐infected adults

Anal cancer is one of the most common non-AIDS-defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV-infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV-related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV-infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV-infected adults.

Recommandations pour la délinéation des aires ganglionnaires pelviennes dans le cancer du canal anal

Squamous cell anal cancer is a rare malignancy, its incidence increases due to higher exposure of the young adults to risk factors. The current management is based on chemoradiotherapy, which is highly effective and achieves locoregional control but causes important morbidity. Improvement of radiation technique such as intensity modulated radiation therapy has led to reduce acute toxicities, but also requires an accurate delineation of the target volumes in order not to underestimate potential and pathological sites resulting in an increase of the locoregional failures. PET scanner has an important place in the pretreatment work-up for staging and targeting the delineation of the volumes, allowing to select patients with localized disease, avoid geographic miss and appropriately boost nodal disease. The study of recurrences sites has not yet provided a real mapping of the recurrences depending on the treatment volumes. Different radiation oncologist cooperative groups have published guidelines and tools for delineation, in order to provide homogeneity but also customize the management of anal carcinoma.