Anal Tumors Research Articles

Mutational analysis of locally advanced rectal cancer and response to neoadjuvant chemoradiation.

449 Background: Preoperative chemoradiation (CRT) is the standard of care for locally advanced rectal adenocarcinoma and leads to pathologic complete response (pCR) rates of 8-20%. pCR has been correlated with improved long term outcomes. Known mutations may contribute to lack of pCR. We retrospectively evaluated our single institution experience to determine rates and potential mutational and clinical predictors of pCR. Methods: With IRB approval, we reviewed 79 consecutive patients with stage II/III rectal adenocarcinoma, diagnosed from 7/2005–6/2010. Patients received preoperative CRT to 50.4 Gy and concurrent 5-FU based chemotherapy prior to total mesorectal excision. Primary endpoint was pCR rate by Dworak tumor regression grade. Mutations were analyzed on pre- and/or post-treatment tissue available for 47 patients with a multiplexed clinical assay on nucleic acid (SNaPshot), which tests for 130 mutations across 15 cancer genes. 32 patients did not have enough tissue for analysis. Other variables including T/N stage, grade, circumferentiality, distance to anal verge, tumor size (continuous, per cm), pre and post-CRT CEA levels, and treatment duration were evaluated using logistic regression analysis. Results: Median age was 58 years and 85% had stage III disease. Among 54% of patients with mutations assessed, the following were present: 37% KRAS, 3% APC, 3% BRAF, 5% NRAS, 4% PIK3CA, 8% TP53. TP53 testing was limited to common mutation sites. In the entire cohort, 20% had a pCR. No patients with BRAF, NRAS or KRAS mutations had a pCR. Patients with a pCR were more likely to have a post-RT CEA ≤ 2.5 (93% vs 62%, p=0.002) and no mutations identified (100% vs 38%, p=0.019). pCR patients had a trend to lower rates of KRAS mutations (0% vs 41%, p=0.1). On UVA, predictors of pCR included: post-RT CEA ≤ 2.5 (OR 8.6, 95% CI 1.03 – 71.9, p=0.047), insufficient tissue to analyze (OR 5.1, CI 1.45-18, p=0.011), and smaller tumor size (OR 0.69, CI 0.48 – 1.0, p=0.05). With a median follow-up of 30 months, there were 3 local and 6 distant recurrences. None with a pCR developed recurrence. Conclusions: Patients with the composite characteristics of being BRAF, KRAS, and NRAS wild type rectal cancer are more likely to have a pCR with preoperative CRT.

Oral cancer, HPV infection and evidence of sexual transmission

The incidence of oropharyngeal cancer and oral cancer is growing worldwide, both in young non-smokers and in young non-drinkers (smoking and drinking are considered the main risk factors). Epidemiologic studies suggest a strong association between the infection by human papillomavirus (HPV), especially types 16 and 18 (high oncological risk) which have already demonstrated their etiological role in anal tumours as well as in cervix cancer. There is clear epidemiologic evidence that both types of tumours relate to changes in sexual behaviour and that both are linked to sexual transmission of HPV. The number of oral and oropharyngeal cancer cases is rising nowadays, especially among young individuals with no typical toxic habits, such as tobacco and/or alcohol. In this review we set out to update the aspects related to the onset of oral cancer, its relationship with HPV infection and whether this association may be due to the sexual transmission of the virus. Key words:Human papillomavirus, oral sex, head and neck cancer, oral cancer, squamous cell carcinoma, oropharyngeal cancer.

20. Utility of human papillomavirus (HPV) 16 E6 and L1 DNA levels for anal cancer screening in HIV-infected individuals

Background In this prospective study we evaluate the sampling performance of HPV16 DNA E6 and L1 levels in detecting anal intraepithelial neoplasm using either a moistened Dacron swab (DS) or cytobrush (CB). Methods: We recruited HIV-infected (n = 57) and organ-transplanted subjects (n = 3) with an abnormal anal Pap smear who presented for high-resolution anoscopy (HRA). Prior to HRA, the first 30 subjects underwent sampling with a moistened DS, and the next 30 with a CB. HRA was then performed in the usual fashion. Samples were tested for HPV16 DNA E6 and L1 DNA using a validated qPCR technique. Anal biopsies were taken as per standard-of-care and categorised as negative, AIN 1/warts, or AIN 2 or 3. Results: 59 of 60 samples had adequate DNA and were evaluated for the comparison of HPV16 E6 and L1 DNA levels. A CB performed better than the DS in detecting low positive and positive levels of HPV16 E6 DNA (P = 0.01). We then further evaluated the correlation of HRA-directed biopsies and HPV16 DNA E6 levels. There was a positive correlation of HRA-directed biopsy results stratified by increasing histological levels with HPV16 E6 DNA (P = 0.018, Kruskal–Wallis test). Conclusions: A CB performed better than DS for molecular HPV testing. If molecular testing is included in anal cancer screening, consideration should be made for co-sampling with both a DS for cytology and CB for HPV testing. Further studies evaluating the sample yields should be performed to assist in implementation of anal cancer screening programs in defined populations of at-risk individuals.

Evaluation of an anal sac adenocarcinoma tumor in a Spitz dog

A 9-year-old emasculated male Spitz with tenesmus and constipation had a subcutaneous mass at the left ventral aspect of the anus with history of polyuria and polydipsia. A complete blood cell count, serum biochemistry panel, and urinalysis (cystocentesis sample) were evaluated. Abnormalities in the serum biochemistry panel included a mildly elevated serum cholesterol concentration (7.28 mmol/L; reference interval, 2.70-5.94 mmol/L), increased serum alkaline phosphatase activity (184 U/L; reference interval, 9-90 U/L), alanine transaminase (122 U/L; reference interval, 5-60 U/L) activity and aspartate aminotransferase (80 U/L; reference interval, 5-55 U/L) activity, severe increased total calcium concentration (16.3 mg/dL; reference interval, 8.2-12.4 mg/dL or 9.3-11.4 mg/dL), and decreased total calcium concentration (3.4 mg/dL, reference interval, 2.5-5.6mg/dL). Furthermore, testing revealed an increased intact parathyroid hormone concentration (38.6 pmol/L; reference interval, 3-17 pmol/L). On cytologic and histopathologic examinations, various types of cells were observed. Most of the cells were oval to polygonal and had elliptical or elongate nuclei and a moderate amount of pale to basophilic cytoplasm. The remaining cells had round to oval nuclei and pale to basophilic cytoplasm. Cells of both types were loosely adhered to each other and were arranged in rosette-like structures. Both neoplastic cell types had fine homogenous chromatin and either a small indistinct nucleolus or no visible nucleolus. Mild anisokaryosis and anisocytosis were observed. Histologically, the mass consists of glandular structures formed by cuboidal cells admixed with bundles of spindle cells. Based on location and histologic features, the final diagnosis was adenocarcinoma of the apocrine gland of the anal sac, which should be included as a cytologic differential diagnosis when spindle cells and typical epithelial cells are observed in masses in the region of the anal sac of dogs.

42. Epigenomic profiling of anal cancer: does size matter? An RTOG 98-11 specimen study

Background Anal cancer accounts for 4% of all lower gastrointestinal tract malignancies in the US. One of the most important predictors of prognosis among anal cancer patients is the size of the primary tumour. Tumours with diameters >5 cm have poorer disease-free survival than those with smaller tumours. Understanding the biological changes associated with tumour growth may provide information to guide therapy and improve patient outcomes. DNA methylation changes are critical epigenetic events in cancer development. Methods: In this study we sought to characterise the epigenomic signatures associated with anal cancer tumour size (≤5 cm vs >5 cm) in FFPE tissues from 121 patients (≤5 cm = 88; >5 cm = 33) who participated in the RTOG 98–11 cooperative group anal cancer clinical trial. Differential methylation, examined at >450 000 CpG loci using the Illumina Human Methylation 450 Array, were compared between the two groups using Mann–Whitney test (significance = P < 0.001 and difference in methylation β-value >0.1). Results: This study included 74 women and 47 men with a median age of 54 years. A total of 86 CpG loci were differentially methylated (78 increased and 8 decreased) in large vs small tumours. Genes harbouring CpG sites that were among the most highly differentially methylated included those associated with WNT signalling (FZD10, WNT9A), microRNAs (MIR200A) and novel methylated targets (PON3). Conclusions: These data provide evidence that epigenetic events likely play a significant role in the progression of anal SCC and may serve as biomarkers of prognosis. Similar epigenomic approaches may be useful at earlier stages of anal neoplastic progression for application in screening and early detection.

Anal Cancer Study Based on Korea Central Cancer Registry Data: One Step Forward in Clinical Research

See Article on Page 182-185 First of all, I would like to congratulate the authors of this work, which focused especially on rare tumors and anal cancer based on National Cancer Registry data. For colorectal surgeons, knowledge of oncologic outcomes for anal cancer is important for making a therapeutic decision. Furthermore, these outcomes should be based on Korean Cancer Registry data. Anal cancer constitutes a relatively small portion of gastrointestinal tract cancers [1]. However, anal cancers are probably underreported because some anal canal tumors are misclassified as rectal tumors. Wide geographical and racial variations in the incidence of cancers are observed around the world. The incidence and the survival rates are generally well publicized for the more common cancers, such as lung, breast, and colorectal tumors; however, little is written regarding the incidence and the survival rates for anal canal cancer. Although some authors have reported clinicopathologic features or prognostic factors for anal cancers [2, 3], the characteristics of and the survival rate for anal cancer in Korea are largely unknown because no population-based study has been performed to address these issues in Korea. For decades, in many countries and regions, registration of cancers has been mandatory. National cancer registration is rooted in public health, helps in the planning of health services, and can be an important tool in clinical research. However, sometimes clinicians are frustrated because the cancer registry cannot provide all the information they need. A limitation in this study based on Korea Central Cancer Registry data is that the database lacks information on interventions such as surgery, radiation, and chemotherapy, on time to any type of recurrence, or on aspects of quality of care for anal canal cancer. The authors compared the survival between males and females by Surveillance, Epidemiology and End Results (SEER) stage and found that survival rates showed a diffference according to sex and age which was related to the distinct features of Korean patients with anal cancer [4]. This study is the largest to date that reports population-based survival data for anal canal cancer in Korea, and it provides an updated picture of anal canal cancer during the past 17 years. Even though the results could be representative of the population in Korea and should be more meaningful than single-institution experiences, this study has some limitations. The study did not analyze oncologic oucomes according to TNM stage, therapeutic modality, or recurrence pattern. In the future, the detailed parameters must be checked before analyzing Korean Cancer Registry database. Additionally, current data needs to be compared with published single-institution anal cancer data. Finally, prospective multicenter studies based using clinical databases on rare cancers need to be done to improve the quality of the data.

Benign anal and perianal polypoid neoplasms and tumor-like lesions

Mesenchymal anal and perianal tumors are relatively uncommon. The majority are malignant. Benign mesenchymal anal tumors are rare. Some are common stromal neoplasms, but with the rare presentation as anal polyps. Other lesions are rare, but unique to the anal/perianal region. Common keratinous cysts might uncommonly present as anal polyps, while other rare cysts are unique to the anogenital region.A retrospective review study of 493 anal and perianal specimens conducted over seven years showed twenty cases (4.0%) of benign anal polypoid lesions. We excluded the usual fibroepithelial polyps, anal tags, papilla, hemorrhoids and warts. We found six cysts, three lipomas, two papillary hidradenomas, two melanocytic nevi, one hamartoma, one xanthogranuloma, one seborrheic keratosis, one hematoma, one fibrous histiocytoma, one granular cell tumor and one lymphangioma. The male to female ratio was 1.5:1. They were found in adults (mean age 37.8years) and in infants (mean age 2.4years). In general, they were smaller than 2cm. They were either asymptomatic or presented with anal pain, bleeding or lumps. Some were clinically confused with the more common non-neoplastic anal tags, hemorrhoids and fibroepithelial polyps/papilla. A variety of common and rare benign lesions might present as anal polyps with important surgical and pathologic challenges and implications.

Anorectal Melanoma Masquerading as Common Hemorrhoids

Introduction: Primary melanoma of the anorectum is a very rare and aggressive malignancy that is found to contribute to 1% of all anorectal malignancies. Usually, it affects women during the fifth and sixth decade of life and patients complain of rectal bleeding that is associated with changes in their bowel habits. Our case report describes a patient with hematochezia who was thought to have benign hemorrhoids but was diagnosed with anorectal melanoma. Case: An 83-year-old Caucasian female with a history of hyperlipidemia and HTN, presented to our office with a chief complaint of intermittent hematochezia for the past 2-3 months. Review of systems was pertinent for vague abdominal discomfort and change in bowel habits on several occasions. On physical exam, vitals were unremarkable; the abdomen was soft with minimal tenderness in the left lower quadrant. There were no masses or enlarged viscera. A digital rectal exam revealed prolapsed internal hemorrhoids. Colonoscopy revealed scattered sigmoid diverticulosis and an equivocal raised, nonpigmented, anorectal lesion that measured 2x1 cm, within the left lateral anal canal. The lesion was thought to be a thrombosed hemorrhoid. Biopsies were taken and results were consistent with malignant melanoma. A CT of chest, abdomen and pelvis demonstrated metastasis to the adrenals, pancreas and kidney. A bone scan performed was negative and an MRCP showed dilatation of pancreatic duct in the tail of pancreas. The patient underwent a transanal excision of anal tumor without any complications. Discussion: Primary melanoma of the rectum is a very rare condition that carries a dismal prognosis. The most common complaint is rectal bleeding but some patients present with anal pain, anal pruritus, tenesmus, and change in bowel habits. Unlike cutaneous melanoma, anal melanoma has no known risk factors. The diagnosis is often delayed and easily confused with common benign hemorrhoids. The median survival rate is 24 months, and a 5-year survival rate of only 15%. Because of the rareness of this condition, there are few guidelines in the approach for treatment depending on the size of the lesion. Radical abdominoperineal resection is effective when the lesion is less than 2 mm wide, whereas wide local excision is applicable with lesions greater than 2 mm. Thus, it is imperative that the diagnosis be made timely so that prompt treatment may be applied. Chemotherapy, radiation therapy, and immune therapy have a limited role. In conclusion, physicians need to be aware of this devastating malignancy that can easily be confused with benign hemorrhoids.

Benign fibrous histiocytoma presenting as anal canal polyp: first case report

Nonepithelial and nonmelanocytic anal neoplasms are uncommon. The majority are mesenchymal tumors, most of which are malignant sarcomas, particularly leiomyosarcomas and gastrointestinal stromal tumors. Benign mesenchymal anal neoplasms are even rarer. The most common reported cases were anal leiomyomas, granular cell tumors, fibroadenomas, and xanthogranulomas. Benign fibrous histiocytomas (BFHs) or dermatofibromas are common mesenchymal cutaneous tumors that occur in different sites and at any age. Review of the literature did not show previous reports of BFH arising in the anal canal region. We report the first case of a solitary BFH, an unexpected occurrence of a common tumor type presenting as a polyp in an unusual site such as the anus. This rare occurrence can present diagnostic challenges for the surgeons and pathologists. Clinically, it can be confused with the usual anal tags, fibroepithelial polyps, or hemorrhoids. Benign fibrous histiocytoma is a neoplasm with a potential of local recurrence and, therefore, carries certain clinical implications for the patients' management and follow-up when compared with the common nonneoplastic causes of anal polyps such as the anal tags of anal fissures, hemorrhoids, or fibroepithelial papilla. Histologically, it should be differentiated from other histiocytic lesions. This can be resolved by the application of certain histologic features with the appropriate immunohistochemical markers taken within the correct clinical context.

Detection of Human Papillomavirus in Small Cell Carcinomas of the Anus and Rectum

Small cell carcinomas represent <1% of colorectal/anal carcinomas and have a poor prognosis. Anorectal squamous cell carcinomas are often associated with high-risk human papillomavirus (HPV) infection, similar to squamous and small cell carcinomas of the uterine cervix. In HPV infection, the oncoprotein E7 inactivates the tumor suppressor Rb, leading to p16 upregulation; however, in small cell carcinomas, the Rb pathway is often blocked by other mechanisms; thus, increased p16 may not indicate HPV infection. P16 immunohistochemistry (IHC) may have a limited role in evaluating small cell carcinomas for HPV infection. Formalin-fixed, paraffin-embedded tissue sections of previously diagnosed small cell carcinomas of the anus (n=5) and rectum (n=11) were subjected to IHC for p16, CDX2, and p63, followed by in situ hybridization for high-risk HPV. All (100%) cases of anal and rectal small cell carcinomas were positive for p16, and 100% of anal and 82% of rectal small cell carcinomas were positive for high-risk HPV. The majority of cases showed low or very low HPV copy numbers. In 6 cases, HPV was detected only by using the HPV-16 genotype-specific assay detecting very low copy numbers (1 to 2 viral copies). The majority of tumors expressed p63, which was more pronounced in the anal tumors. CDX2 expression was observed predominantly in rectal tumors. High-risk HPV can be detected using in situ hybridization in the majority of anorectal small cell carcinomas, which are uniformly p16 positive by IHC. HPV-targeted therapy could result in better control of these aggressive neoplasms.

Basosquamous Cell Carcinoma of the Anus

Cancer of the anus is a rare neoplasm in the general population and accounts for only about 1.2–2 % of gastrointestinal cancers [1–3]. Anal carcinoma usually appears in the fifth and sixth decades of life and shows a female predominance [1–3]. Regarding anatomy, anal carcinomas are divided into those occurring within the anal canal and those occurring at the anal verge [1]. The most common malignant anal tumor is squamous cell carcinoma and its variants whereas other more rare lesions include adenocarcinoma, small cell carcinoma, undifferentiated carcinoma, melanoma, lymphoma sarcoma, and perianal basal cell carcinoma [1–3]. Basal cell carcinoma is a very rare anal tumor of the anal margin representing only 0.2 % of the anorectal tumors [1, 4] and with only a few more than a hundred cases having been reported [5]. Clinically, the cancer presents usually as a slowly growing sharply marginated area with raised edges and central ulceration which can extend into the anal canal to the squamous zone [3–5]. We present a very rare case of basosquamous carcinoma of the anus and emphasize this rare aggressive variant of basal cell carcinoma and its differential diagnosis from basaloid carcinoma an aggressive variant of squamous cell carcinoma.

Double anal canal cancers associated with a long history of perianal Paget’s disease: report of a case

Extramammary Paget's disease (EPD) is rare. We report a case of double anal canal cancers in a patient with a long history of perianal Paget's disease. The patient, a 68-year-old Japanese woman, refused surgery initially and was treated with electron beam therapy, which achieved remission. However, 6 years later, Paget's disease was found to be progressing again and double anal canal tumors were also detected in the proctos and external skin area. We performed abdominoperineal resection (Miles' operation) and lymph node dissection for the Paget's disease with double anal canal tumors. Immunohistochemical staining revealed cytokeratin (CK)-20 expression in the adenocarcinomas and Paget's disease lesion, but not CK-7 or gross cystic disease fluid protein-15 expression. The lesion was joined to the carcinoma by a stalk. The immunohistochemistry results suggested secondary EPD, although it was originally considered to be Paget's carcinoma (primary EPD) based on the clinical history.

Influencing factors related to lymphatic metastasis of T2 rectal carcinoma

To study the risk factors associated with lymphatic metastasis of T2 rectal carcinoma. A consecutive series of 122 patients with T2 rectal cancer who underwent radical surgery in the First Affiliated Hospital of Fujian Medical University from 2006 to 2011 were included for retrospective analysis. Risk factors associated with lymphatic metastasis were investigated. The rate of lymph node metastasis was 21.3% (26/122). Distance to anal verge(P<0.05), morphological type(P<0.05), histological type(P<0.05), tumor differentiation(P<0.05), and depth of invasion(P<0.05) were risk factors for lymph node metastasis in T2 rectal cancer by univariate analysis. The depth of invasion remained statistically significant by multivariate analysis. The rate of lymph node metastasis was 13%(7/54) in patients with shallow muscularis propria involvement, and 28%(19/68) in those with deep muscularis involvement. For T2 rectal cancer with shallow muscularis involvement, the risk of lymph node metastasis is low and transanal excision should be considered.

The burden of hospitalizations for anus and penis neoplasm in Spain (1997–2008)

An epidemiological retrospective study has been performed to assess the burden of hospitalization by anus and penis neoplasm in the general population in Spain. All hospital discharges and deaths related to anal malign neoplasm and penile malign neoplasm from 1997 to 2008 in Spain were obtained. A total of 19,608 hospital admissions were recorded during the study period: 11,965 were related to anal malign neoplasm (4,992 in women and 6,973 in men) and 7,643 to penis malignant neoplasm. This corresponds to a hospitalization rate of 1.97 (CI 95%: 1.91–2.02) hospitalizations per 100,000 women/ year, 2.84 (CI 95%: 2.77–2.91) hospitalizations per 100,000 men/ year and 3.11 (CI 95%: 3.04- 3.18) hospitalizations per 100,000 men/ year, respectively during the study period. The hospitalization rate increased significantly during the study period in all locations. It also increased significantly with age for all locations. Hospitalization and mortality rates in men were 50% higher than in women A total of 530 deaths related to penis malignant neoplasm and 738 deaths related to anus malignant neoplasm in men and 488 in women were reported during the 12-y study period. Although a decrease in smoking prevalence has led to a decrease in the incidence of cancers in the last decade, the hospitalizations due to anal and penile malign neoplasm have not declined in our study. This might be attributed to a high prevalence of HPV infection in these particular genital malign neoplasms.

Variation in gross tumor volume delineation using CT, MRI, and FDG-PET in planning radiotherapy of anal cancer.

652 Background: Radiotherapy (RT) outcome depends on accurate delineation of gross tumor volume (GTV) regarding tumor size and position. CT and MRI are standard image modalities as they provide the necessary structural information. Positron emission tomography with flourodeoxyglucose (FDG-PET) visualizes glucose metabolism in active tumor tissue. The main objective was to explore the intra-observer and inter-modality variation of the GTV delineated on CT, MRI and PET images. Methods: Between November 2006 and July 2009, 22 patients with biopsy-proven anal carcinoma stage T1-T4/N0-3/M0-1 scheduled for curative RT were included in the study. All patients underwent FDG-PET/contrast enhanced CT and MRI. The delineations of GTV were done twice for each imaging modality with a minimum of 3 months in between. Delineations on the CT and MRI were done by routine methods. For the PET part three different cut-off values were used: SUV 2.5, 40% and 50% of maximum SUV. Non-overlap was calculated by subtracting the intersection from the union of two sets both regarding intra-observer variation and inter-modality variation. The GTV were compared for size, intra-observer variation and non-overlap using Wilcoxon rank sum test, where p &lt; 0.05 was considered significant. Results: Volume size: the median GTV-CT was 25.6 cm3 which was significantly larger compared to GTV-MRI (7.2 cm3) and the GTV from the different PET cut offs (6.2 cm3, 10.6 cm3 and 7.0 cm3). Intra-observer variation: the median GTV delineated on CT, MRI and PET did not vary significant between delineation number 1 and 2. Non-overlap: the non-overlapping regions in GTV between delineation 1 and 2 using CT and MRI (20.5% and 22.5%) were significantly different from the PET cut offs (5.5% , 6.4% and 5.8%). Conclusions: Delineation of anal tumors is difficult; CT gives rise to the largest GTV with considerable intra-observer variation. MRI has the same degree of inaccuracy, but smaller GTV. PET-GTVs are the smallest with significant smaller intra-observer uncertainty.

Anal Myolipoma: A New Benign Entity in Patients with an Anal Tumor?

A myolipoma is an extremely rare benign neoplasm, occurring most frequently in adults in the deep soft tissue of the abdomen or retroperitoneum. We experienced a case of an anal myolipoma occurring in a 30-year-old woman, and it was surgically resected. To our knowledge, this is the first reported case of a myolipoma arising from the anus, so such a possibility needs to be considered in the differential diagnosis.

MicroRNA-15b is induced with E2F-controlled genes in HPV-related cancer

Background:MicroRNAs (miRNAs) are important regulators of cellular processes and are found to be deregulated in many cancers. We here analysed the miRNA expression in anal carcinomas. In a previous study, we found that our anal carcinoma tumours were divided into two groups based on the expression of E2F-regulated genes. Therefore, we searched for miRNAs that could reproduce this grouping.Methods:A global screen of the miRNA population was performed using real-time quantitative PCR (RT–qPCR) array methods and differentially expressed miRNAs were identified. Real-time–qPCR was used to verify the expression levels of selected miRNAs and genes in a larger collection of biopsies. A siRNA-mediated knockdown of human papilloma virus (HPV)16 E7 in a cervical cell line was performed to assess the effect of E7 on miR-15b.Results:The grouping of tumours into two groups based on the expression of E2F-controlled genes was confirmed in a larger collection of anal carcinoma tumours. The expression of miR-15b was shown to be highly correlated with that of five selected E2F-induced genes (CCNA2, CCNB1, CCNB2, MSH6 and MCM7). A knockdown of HPV16 E7 resulted in decreased levels of miR-15b in Ca Ski cells.Conclusion:MiR-15b expression correlates with E2F-regulated genes in anal carcinoma and appears to be part of the E2F-regulatory network.

Dominant role of HPV16 E7 in anal carcinogenesis

Ninety percent of anal cancer is associated with human papilloma viruses (HPVs). Using our previously established HPV transgenic mouse model for anal cancer, we tested the role of the individual oncogenes E6 and E7. K14E6 and K14E7 transgenic mice were treated with dimethylbenz[a]anthracene (DMBA) to the anal canal and compared to matched nontransgenic and doubly transgenic K14E6/E7 mice. K14E7 and K14E6/E7 transgenic mice developed anal tumors (papillomas, atypias and carcinomas combined) at significantly higher rates (88% and 100%, respectively) than either K14E6 or NTG mice (18% and 19%, respectively). Likewise, K14E7 and K14E6/E7 transgenic mice developed frank cancer (carcinomas) at significantly higher rates (85% and 85%, respectively) than either K14E6 or NTG mice (18% and 10%, respectively). These findings indicate that E7 is the more potent oncogene in anal cancer caused by HPVs.

Anus neoplasm: study of a case series

Anus neoplasm accounts for 2 to 4% of colorectal tumors, being more prevalent around the seventh and the eighth decades. Females are mostly affected, and the ratio is 3:1. Its increased prevalence amongst the population in the past years is probably related to the higher number of people that are affected by sexually transmitted diseases, mainly human papillomavirus (types 16 and 18, mostly) and/or the human immunodeficiency virus. Diagnosis is based on clinical findings and anatomopathological tests. The treatment of choice is radiochemotherapy, and the rescue surgery with abdominoperineal resection is used for recurrence and persistence cases. A retrospective and prospective longitudinal observational study was performed with 11 patients diagnosed with anal neoplasm from 2004 to 2010. Six (54.5%) were females and five (45.5%) were males. The incidence was higher in the sixth decade, at the mean age of 54.45 years. The most frequent histological type observed was the epidermoid carcinoma, and the most frequent cell differentiation type was the moderately differentiated. Chemotharapy associated with radiotherapy was used in 81.9% of the patients, and abdominoperineal resection was necessary as a rescue surgery in 18.2% of the patients.

Four decades of anal cancer in Tasmania, Australia: what do the case data tell us?

Anal cancer is a rare cancer analogous to cervical cancer, largely caused by exposure to oncogenic human papillomavirus. We have sought to study this disease in the epidemiologically distinct population of Tasmania. Medical records at all tertiary and secondary referral centres in Tasmania were audited for records with corresponding International Classification of Diseases (ICD)-10 codes. Statistical significances of trends were evaluated using Fisher's exact test, logistic regression or linear regression. Of ~1350 screening records, 170 cases of anal cancer were found with patient presentation during 1973-2010, corresponding to 132 patients. This cohort was mostly female (66.7%), with squamous cell histology (81.8%) and anal canal primaries (72.0%). Most cases were detected at Stage II or below and the majority remained disease-free after treatment. Relatively few cases had documentation of typical risk factors for anal cancer, such as HIV seropositivity, a history of cancer or smoking. After 2000, there was a trend towards a lower stage at presentation, correlating with an increased 5-year survival. After 2000, no anal margin tumours presented beyond Stage II; nearly half were detected in situ and none were fatal. For anal canal tumours, there was virtually no change in the mean stage at detection or in survival. This is the first case series of anal cancer in Tasmania. We find that in many ways, including symptoms and pathology at presentation, epidemiology is typical. However, our cohort is distinct in its paucity of known risk groups, including HIV-positive people, those with a history of cancer and smokers.