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Cancer Cytopathology Feb 2011Cervical cancer and anal cancer share many similarities including causation by oncogenic human papillomaviruses; however, significant differences exist in their... (Review)
Review
Cervical cancer and anal cancer share many similarities including causation by oncogenic human papillomaviruses; however, significant differences exist in their epidemiology, risk factors, biologic behavior, management, and treatment. Although rare, the incidence of anal cancer is alarmingly high and continues to increase in high-risk populations, particularly men who have sex with men regardless of their human immunodeficiency virus (HIV) status. There are no national screening guidelines for anal cancer. Using the success of cervical cancer screening as a model, anal cancer screening approaches apply anal cytology, high-resolution anoscopy, and directed biopsy to guide treatment and management strategies. Although much has been learned about the natural history and epidemiology of anal intraepithelial neoplasia (AIN), the rate of progression of high-grade anal intraepithelial neoplasia (HGAIN) to invasive squamous cell carcinomas is not known. The impact of screening and treatment of HGAIN on morbidity and mortality from anal cancer are also unknown. Because the incidence of HGAIN and anal squamous cell carcinoma continue to increase, it is imperative to find pathways for effective screening, early detection, and therapeutic intervention. This article provides an overview of anal cancer screening while highlighting its differences from cervical cancer screening and the remaining obstacles and controversies to implementation of a successful anal cancer screening program.
Topics: Anus Neoplasms; Cytodiagnosis; Diagnosis, Differential; Early Detection of Cancer; Female; Humans; Male; Uterine Cervical Neoplasms
PubMed: 21319310
DOI: 10.1002/cncy.20126 -
In Vivo (Athens, Greece) 2022Chemoradiation is the recommended initial treatment for locally advanced squamous anal cancer. However, there is still no consensus on the course of treatment for anal...
BACKGROUND/AIM
Chemoradiation is the recommended initial treatment for locally advanced squamous anal cancer. However, there is still no consensus on the course of treatment for anal canal cancer with distant metastasis, and the significance of surgical resection of distant metastases is also unclear.
CASE REPORT
A 48-year-old woman presented to the referral hospital complaining of prolonged bleeding for the past 6 months. On examination, a mass was identified in the anal canal and the upper part of the rectum that was diagnosed as squamous cell carcinoma. Liver, ovarian, and right internal iliac lymph node metastases were found on further examination, and the patient was referred to our department for treatment. Systemic chemotherapy was planned, and six courses of modified FOLFOX6 were administered. After chemotherapy, the liver and right internal iliac lymph node metastases tended to shrink, and no new lesions appeared. Therefore, a total posterior pelvic resection and a bilateral lymph node dissection were performed for the primary tumour and ovarian metastases, and a simultaneous laparoscopic right partial hepatectomy was undertaken for the liver metastases. R0 resection was achieved, and the final diagnosis was T3N3M1a(H) stage IV. The patient remains alive 2 years after the surgery without recurrence.
CONCLUSION
We report a rare case of anal canal cancer with distant metastases who achieved R0 resection after modified FOLFOX6 chemotherapy.
Topics: Female; Humans; Middle Aged; Lymphatic Metastasis; Ovary; Anus Neoplasms; Carcinoma, Squamous Cell; Liver
PubMed: 36309369
DOI: 10.21873/invivo.13048 -
Scientific Reports Feb 2021Archival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral... (Observational Study)
Observational Study
Archival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral HPV16-positive metastasis were retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Full length nucleotide sequences of the same HPV16 were identified from the initial and second anal biopsy samples, from plasma sample and from vertebral metastasis biopsy. Remarkably, HPV was episomal in each sample. The HPV genome sequence was closest to the HPV16 Qv18158E variant subtype (A1 lineage) exhibiting base substitutions and deletions in 7 and 2 HPV loci, respectively. In conclusion, the powerful Capt-HPV followed by NGS allows evidencing the detailed cartography of tumoral and circulating HPV DNA, giving rise to a unique and unexpected episomal virus molecular status in a context of aggressive carcinoma, underlying the importance of HPV status and its association with clinical features for further prospective studies.
Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Human papillomavirus 16; Humans; Neoplasm Metastasis; Papillomavirus Infections; Retrospective Studies
PubMed: 33633240
DOI: 10.1038/s41598-021-84110-2 -
Modern Pathology : An Official Journal... May 2021Squamous cell carcinoma (SqCC) is the most common malignancy of the anal canal, where it is strongly associated with HPV infection. Characteristic genomic alterations...
Squamous cell carcinoma (SqCC) is the most common malignancy of the anal canal, where it is strongly associated with HPV infection. Characteristic genomic alterations have been identified in anal SqCC, but their clinical significance and correlation with HPV status, pathologic features, and immunohistochemical markers are not well established. We examined the molecular and clinicopathologic features of 96 HPV-positive and 20 HPV-negative anal SqCC. HPV types included 89 with HPV16, 2 combined HPV16/HPV18, and 5 HPV33. HPV-positive cases demonstrated frequent mutations or amplifications in PIK3CA (30%; p = 0.027) or FBXW7 mutations (10%). HPV-negativity was associated with frequent TP53 (53%; p = 0.00001) and CDKN2A (21%; p = 0.0045) mutations. P16 immunohistochemistry was positive in all HPV-positive cases and 3/20 HPV-negative cases (p < 0.0001; sensitivity: 100%; specificity: 85%) and was associated with basaloid morphology (p = 0.0031). Aberrant p53 immunohistochemical staining was 100% sensitive and specific for TP53 mutation (p < 0.0001). By the Kaplan-Meier method, HPV-negativity, aberrant p53 staining, and TP53 mutation were associated with inferior overall survival (OS) (p < 0.0001, p = 0.0103, p = 0.0103, respectively) and inferior recurrence-free survival (p = 0.133, p = 0.0064, and p = 0.0064, respectively). TP53/p53 status stratified survival probability by HPV status (p = 0.013), with HPV-negative/aberrant p53 staining associated with the worst OS, HPV-positive/wild-type p53 with best OS, and HPV-positive/aberrant p53 or HPV-negative/wild-type p53 with intermediate OS. On multivariate analysis HPV status (p = 0.0063), patient age (p = 0.0054), T stage (p = 0.039), and lymph node involvement (p = 0.044) were independently associated with OS. PD-L1 expression (CPS ≥ 1) was seen in 30% of HPV-positive and 40% of HPV-negative cases, and PD-L1 positivity was associated with a trend toward inferior OS within the HPV-negative group (p = 0.064). Our findings suggest that anal SqCC can be subclassified into clinically, pathologically, and molecularly distinct groups based on HPV and TP53 mutation status, and p16 and p53 immunohistochemistry represent a clinically useful method of predicting these prognostic groups.
Topics: Adult; Anus Neoplasms; Carcinoma, Squamous Cell; DNA Mutational Analysis; Female; High-Throughput Nucleotide Sequencing; Humans; Immunophenotyping; Male; Middle Aged; Mutation; Papillomavirus Infections; Prognosis; Tumor Suppressor Protein p53
PubMed: 33483624
DOI: 10.1038/s41379-020-00729-y -
F1000Research 2018Anal cancer is a rare condition, although its incidence has been increasing over the past several decades, particularly in women. The majority of anal cancers are... (Review)
Review
Anal cancer is a rare condition, although its incidence has been increasing over the past several decades, particularly in women. The majority of anal cancers are squamous cell cancers and are linked with human papilloma virus (HPV) infection. Recent work in HPV basic science has delineated the mechanism by which the virus leads to the development of anal cancer. With widespread availability of an HPV vaccine since 2006, vaccination has become an important strategy for anal cancer prevention. However, in the US, there remain no guidelines for anal cancer screening. Treatment of anal cancer is dictated largely by accurate staging, which is generally accomplished with a combination of physical exam, magnetic resonance imaging, computed tomography, and positron emission tomography. Chemoradiation remains the mainstay of treatment for most patients, with surgery reserved for salvage therapy. Recent trials have identified the optimal use of available chemotherapeutics. Exciting developments in immune therapies targeting HPV oncoproteins as well as therapeutic vaccines may soon dramatically change the way patients with anal cancer are managed.
Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Disease Management; Female; Humans; Male; Neoplasm Staging; Papillomavirus Infections; Papillomavirus Vaccines
PubMed: 30345012
DOI: 10.12688/f1000research.14518.1 -
British Journal of Cancer Jan 2017Squamous cell carcinomas of the anus and anal canal represent a model of a cancer and perhaps the first where level 1 evidence supported primary chemoradiotherapy (CRT)... (Review)
Review
Squamous cell carcinomas of the anus and anal canal represent a model of a cancer and perhaps the first where level 1 evidence supported primary chemoradiotherapy (CRT) in treating locoregional disease with curative intent. The majority of tumours are associated with infection with oncogenic subtypes of human papilloma virus and this plays a significant role in their sensitivity to treatment. However, not all tumours are cured with CRT and there remain opportunities to improve outcomes in terms of oncological control and also reducing late toxicities. Understanding the biology of ASCC promises to allow a more personalised approach to treatment, with the development and validation of a range of biomarkers and associated techniques that are the focus of this review.
Topics: Anus Neoplasms; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Viral; Chemoradiotherapy; Humans; Papillomaviridae
PubMed: 27923035
DOI: 10.1038/bjc.2016.398 -
Current Opinion in HIV and AIDS Jan 2009The incidence of human papillomavirus (HPV)-related cancers has increased among people with HIV infection compared with the general population. This review will describe... (Review)
Review
PURPOSE OF REVIEW
The incidence of human papillomavirus (HPV)-related cancers has increased among people with HIV infection compared with the general population. This review will describe recent findings in HPV-associated cancer incidence since the introduction of antiretroviral therapy, HPV/disease prevalence at sites other than cervix and anus, and recent data on screening and treatment of anal intraepithelial neoplasia.
RECENT FINDINGS
Consistent with high prevalence of anogenital HPV infection, new data on cervical intraepithelial neoplasia and anal intraepithelial neoplasia in HIV-positive men and women show that the incidence of cervical cancer has not declined since the introduction of antiretroviral therapy and that the incidence of anal cancer is rising. Several studies also highlight high rates of HPV infection and HPV-associated disease at sites other than the cervix and anus, including the penis and the mouth. Treatment methods for anal intraepithelial neoplasia have been described and show reasonable efficacy.
SUMMARY
New data imply that the problem of HPV-related cancers will not decline among HIV-positive men and women in the antiretroviral therapy era, highlighting the need to perform studies to determine if screening and treatment of anal intraepithelial neoplasia will prevent development of anal cancer. Recent data show progress in both these areas.
Topics: Anti-Retroviral Agents; Anus Neoplasms; Carcinoma in Situ; Early Detection of Cancer; Female; HIV Infections; Humans; Laser Therapy; Male; Mass Screening; Papillomavirus Infections; Risk Factors; Uterine Cervical Neoplasms
PubMed: 19339939
DOI: 10.1097/COH.0b013e32831a7246 -
Modern Pathology : An Official Journal... Jan 2021Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades...
Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16 status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16 status, cTNM classification as well as both CD3 and CD4 T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.
Topics: Adult; Aged; Algorithms; Anus Neoplasms; Carcinoma, Squamous Cell; Female; Humans; Incidence; Male; Middle Aged; Prognosis; Progression-Free Survival; Treatment Outcome
PubMed: 32728225
DOI: 10.1038/s41379-020-0637-6 -
Cancer Medicine Jul 2022Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi-institutional study was...
Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi-institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above-mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b.
Topics: Adenocarcinoma; Anal Canal; Anus Neoplasms; Carcinoma, Squamous Cell; Humans; Japan; Retrospective Studies
PubMed: 35274487
DOI: 10.1002/cam4.4631 -
European Radiology Aug 2022To assess the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for...
OBJECTIVES
To assess the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for response assessment post curative-intent chemoradiotherapy (CRT) in anal squamous cell carcinoma (ASCC).
METHODS
Consecutive ASCC patients treated with curative-intent CRT at a single centre between January 2018 and April 2020 were retrospectively identified. Clinical meta-data including progression-free survival (PFS) and overall survival (OS) outcomes were collated. Three radiologists evaluated PET-CT and MRI using qualitative response assessment criteria and agreed in consensus. Two-proportion z test was used to compare diagnostic performance metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy). Kaplan-Meier analysis (Mantel-Cox log-rank) was performed.
RESULTS
MRI (accuracy 76%, PPV 44.8%, NPV 95.7%) and PET-CT (accuracy 69.3%, PPV 36.7%, NPV 91.1%) performance metrics were similar; when combined, there were statistically significant improvements (accuracy 94.7%, PPV 78.9%, NPV 100%). Kaplan-Meier analysis demonstrated significant differences in PFS between responders and non-responders at PET-CT (p = 0.007), MRI (p = 0.005), and consensus evaluation (p < 0.001). Cox regression analysis of PFS demonstrated a lower hazard ratio (HR) and narrower 95% confidence intervals for consensus findings (HR = 0.093, p < 0.001). Seventy-five patients, of which 52 (69.3%) were females, with median follow-up of 17.8 months (range 5-32.6) were included. Fifteen of the 75 (20%) had persistent anorectal and/or nodal disease after CRT. Three patients died, median time to death 6.2 months (range 5-18.3).
CONCLUSION
Combined PET-CT and MRI response assessment post-CRT better predicts subsequent outcome than either modality alone. This could have valuable clinical benefits by guiding personalised risk-adapted patient follow-up.
KEY POINTS
• MRI and PET-CT performance metrics for assessing response following chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC) were similar. • Combined MRI and PET-CT treatment response assessment 3 months after CRT in patients with ASCC was demonstrated to be superior to either modality alone. • A combined MRI and PET-CT assessment 3 months after CRT in patients with ASCC has the potential to improve accuracy and guide optimal patient management with a greater ability to predict outcome than either modality alone.
Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Epithelial Cells; Female; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Male; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies
PubMed: 35274187
DOI: 10.1007/s00330-022-08648-z