This document summarizes information about anal canal cancer, including: - It accounts for 1-2% of large bowel malignancies and is increasing in incidence. Risk factors include HPV infection and HIV infection. - Screening high-risk groups like HIV+ individuals can detect early anal intraepithelial neoplasia, as HPV vaccines may help prevent cancers. - Most anal canal cancers are squamous cell carcinomas. Clinical staging evaluates tumor extent, node involvement, and distant spread through digital exam, imaging and biopsy.

1. Ca Anal Canal Part -II
By-Dr Satyajeet Rath
Guide-Prof Kamal Sahni
Dr Himanshu Mishra

2. Introduction
• 1% to 2% of all large bowel malignancies
• incidence is steadily increasing
• median age at diagnosis (anal canal, and anorectal cancers )was 60 years
during 2006 to 2010
• Unique amongst gastrointestinal malignancies in that it has a low
propensity for metastatic spread, making local–regional control a
paramount endpoint in the approach to this disease

3. Risk Factors

4. HPV Infection
• High-risk HPV type-16 has been detected in almost 80-90% of cases of
squamous cell carcinoma of the anus. (to a lesser extent, types 18, 31, 33, 35,
and others.)
• Approximately 80% of anal cancers demonstrated more than one HPV
genotype.
• Incidence 15 times higher in homosexual men than in heterosexual men.
• The anal infection with HPV is mostly sexually transmitted, and the risk for
cancer is increased in patients with a history of receptive anal intercourse in
women and homosexual activity in men.
• It is also been shown that women with high-grade cervical or vulvar dysplasia
are more susceptible to develop anal cancer, as cervical or vulvar HPV infection
escalates anal HPV infection risk.
Grulich AE, Poynten IM, Machalek DA, et al. The epidemiology of anal cancer. Sex Health 2012;9:504–508.
Machalek DA, Poynten M, Jin F, et al. : a systematic review and meta-analysis. Lancet Oncol 2012;13:487–500.

5. HIV Infection
• Incidence of anal cancer in patients who are infected with HIV is estimated to be
twice that of HIV-negative patients.
• Highly active antiretroviral therapy (HAART) has resulted in patients with HIV
living longer and the development of related malignancies.
• In contrast to other HIV-associated malignancies, the incidence of anal cancer
has actually risen following implementation of HAART.
• According to the National Cancer Institute (NCI), the rise in anal cancer
incidence rates during 1980 to 2005 was predominantly seen in male patients
with HIV, relative to their female counterparts.
• HIV-positive patients with anal cancer tended to develop earlier recurrences than
HIV-negative patients by 20 months, although the median survival ( around 35
mnths ) were similar.
Shiels MS, Pfeiffer RM, Chaturvedi AK, et al. Impact of the HIV epidemic on the incidence rates of anal cancer in the United States. J Natl
Cancer Inst 2012;104:1591–1598.

6. Other Risk Factors
• According to the American Society of Colon and Rectal
Surgeons (ASCRS), risk factors other than HIV and HPV
infections include:
• Age: 67% >55 years.
• Smoking: risk factor for anal cancer development.
• Benign anal lesions are no longer thought to contribute to the
development of this disease, although anal cancers are frequently
misdiagnosed as these conditions.

7. Immunosuppression
• Solid organ transplant recipients with chronic immunosuppressive
therapy have a six times higher risk to develop anal cancer relative to the
general population.
• A national cohort study in Sweden of 5,931 patients who had undergone
organ transplantation showed a 10-fold excess risk of developing anal
cancer.
* Adami J, Gabel H, Lindelof B, et al. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br J Cancer 2003;89:1221–1227.
* Grulich AE, van Leeuwen MT, Falster MO, et al. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant
recipients: a meta-analysis. Lancet 2007;370:59–67.

8. Screening & Prevention
• No published guidelines that recommend screening of the general population
• There are high-risk groups that may benefit from such, most prominently patients
infected with HIV
• The rationale for screening for SIL is based on the following:
• there is a high incidence of the anal cancer within the proposed screening population
(i.e., HIV-positive patients),
• available screening tests are effective and cost-efficient
• early detection can change the outcome of the disease.
• The initial recommended screening test is an “anal Pap smear” that evaluates cells
in the anal canal for abnormal cytology through swabbing.
• Patients with abnormal cytology should then be evaluated by high-resolution
anoscopy, which facilitates the visualization of abnormal lesions, allowing biopsy
and/or removal.
Gimenez F, Costa-e-Silva IT, Daumas A, et al. Arq Gastroenterol 2011;48:136–145.

9. Role of Vaccination
• A promising strategy for the prevention of anal dysplasia and malignancy is HPV
vaccination.
• Two vaccines (Cervarix and Gardasil) are now approved by the U.S. Food and
Drug Administration and have been shown to protect against cervical cancer in
women.
• The quadrivalent HPV vaccine Gardasil has demonstrated efficacy for prevention
of HPV 6-, 11-, 16-, and 18-related genital warts and has been shown to protect
against cancers of the anus, vagina, and vulva.
* Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 2011;365:1576–1585.

10. Contd..
• In a large, double blind study, (Palefsky et al)
• 602 healthy homosexual men were randomized to receive the quadrivalent HPV
vaccine versus placebo.
• With a 36-month median follow-up for the development of AIN and/or high-
risk HPV infection
• significantly reduced rates of
• high-grade anal dysplasia
• high-risk HPV infection were demonstrated in the vaccinated group.
• With limited availability and suboptimal outcomes of AIN screening
programs, vaccination may reflect the best long-term approach for reducing
anal cancer risk
* Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 2011;365:1576–1585

11. Pathology
• The typical gross
appearance of SCC of the
anal canal consists of a
lesion with rolled edges,
often with central
ulceration, with a
minority consisting of
polypoid lesions.
Histopathological
Classification
• SCC
• Adenocarcionoma
• Neuroendocrine Tumour
• Carcinoid
• Small cell carcinoma
• High Grade NE tumour
• Melanoma
• Sarcoma
• Lymphoma
It should be noted that histology is
generally more important than
location within the anal canal and
usually dictates overall patient
management.

12. Pathology
• The vast majority of anal canal tumors are classified as SCC ( 85-90 %)
• It encompasses tumors previously described as
• Basaloid
• Cloacogenic
• transitional
• mucoepidermoid
• verrucous mucoepidermoid varieties
• From a treatment standpoint, these are all approached as SCC.
• The majority of these are nonkeratinizing, although tumors arising below the
dentate line often display keratinizing properties.
• Most squamous lesions are moderately to poorly differentiated and display
koilocytic changes consistent with HPV infection.
• The remaining 10% to 15% are predominantly adenocarcinomas, most of
which arise from anal glands or within anal fistulae.
• Adenocarcinomas from the rectal-type mucosa in the upper canal are
classified as primary rectal cancers.

13. AIN-multifocal process associated with HPV, analogous to cervical dysplasia.
Scholefield JH, Castle MT, Watson NF. Malignant transformation of high-grade anal intraepithelial neoplasia. Br J Surg 2005;92:1133–1136.

14. • There is a progression from normal epithelium to condyloma and grade I
AIN (associated with mild dysplasia), later progressing to grade II AIN (with
moderate dysplasia), and ultimately grade III AIN with severe dysplasia, as
well as in situ disease.
• Once disease has reached grade III AIN, it rarely regresses.
• It has been estimated that approximately 1% of AIN III patients progress to
invasive malignancy, annually.
• This incidence of progression of AIN III is substantially increased in patients
who are immunocompromised.
• The prevalence of AIN among HIV-negative homosexual men is high
(>36%), and almost universal among HIV-positive homosexual men.
Perez,Principles and Practices of Radiation Oncology,6th edition

15. Clinical Presentation
• Most common presentation - bleeding from the anus.
• Symptoms of anal cancer can be diverse and include
• Pain
• sensation of a mass
• itching
• anal discharge
• Tenesmus
• sense of fullness
• lump in the anal canal.
• More extensive lesions may present with more ominous symptoms such as
incontinence, passage of gas or stool from the vagina, or significant change
in bowel habits.
• 20% of patients are initially asymptomatic.
• Symptoms may often be dismissed as hemorrhoids or other benign causes,
and it is crucial to further evaluate by a physical examination and anoscopy.
• Any mass should be biopsied for a diagnosis.

16. Clinical staging is performed by a combination of clinical,
endoscopic, and radiographic examinations
• Detailed history including an assessment of anal sphincter function as well
as HIV risk factors.
• Digital rectal examination to identify
• Tumor location , fixation & extent
• fixation to the sphincter complex or
• adjacent organs such as the vagina and prostate.
• Proctoscopy provides
• information about the extent of mucosal spread, including the relationship to the dentate
line, and
• facilitates biopsy.
• It may be necessary to examine patients under anesthesia secondary to pain
and sphincter muscle spasms.

17. • Female patients should undergo a gynecologic examination to determine
vaginal involvement and to exclude other HPV-associated cancers, including
evaluation of the cervix.
• Examination of Inguinal nodes
• Of all patients presenting with palpable inguinal lymph nodes, only 50% are
malignant; therefore, fine-needle aspiration is often recommended in
suspected cases, and a positive result may guide radiation field design and
dose.
• Complete blood counts with serum biochemistry including HIV/CD-4 levels
in the presence of risk factors

18. Imaging
• Imaging is used to better delineate the local extent of disease and regional
adenopathy, and to determine the presence of distant metastases.
• CT Scan is valuable in the pre- and posttreatment assessment of the anorectal
musculature and perirectal nodes
• MRI is considered the most accurate method for assessing the primary cancer
and pelvic nodes.
• Thoracic, abdominal, and pelvic CT and pelvic MRI identify liver or lung
metastases or enlarged nodes.
• If the diagnosis is uncertain, image-guided biopsy should be considered.
• EUS under anaesthesia may be useful in assessing the depth of invasion , but it
has not been validated as an imaging tool.

19. • SLN Biopsy
• Some oncologists have suggested a routine sentinel lymph node (SLN)
evaluation as a staging technique.
• A systematic review of 16 published series evaluating the outcome of SLN
biopsy of inguinal nodes included 323 patients, and the success in identifying
the SLN was 86%.
• However, the exact role of SNL in the pretreatment evaluation remains
undetermined.
• PET Scan
• FDG-PET scans with CT scans as part of the staging evaluation, notably for
patients with T2-4N0 disease or those with involved lymph nodes have been
used.
• But the role of SLN Biopsy and PET Scan are as of yet unproven value in the
initial diagnosis of Ca anal canal.
Tehranian S, Treglia G, et al. Sentinel node mapping in anal canal cancer: systematic review and meta-analysis. J Gastrointestin Liver Dis 2013;22:321–328.
Sveistrup J, Loft A, et al. PET/computed tomography in the staging and treatment of anal cancer. Int J Radiat Oncol Biol Phys 2012;83:134–141.

20. Prgnostic Factors - Tumour factors
• most adverse factor for survival is the presence of extrapelvic metastasis.
• size of the primary tumor is the most useful predictor for local control and
preservation of anorectal function and survival(RTOG 98-11 & EORTC 22861)
• Male sex is also an adverse risk factor
• Involvement of regional lymph nodes is an adverse factor for survival
• In a study of 19,199 patients
• Patients with distant metastases had a 5-year survival of 18.7% versus 59.4% for
those without metastases.
• Patients with regional node metastases had a 5-year survival of 37.4% versus 62.9%
in node-negative patients.

21. Patient factors
• Age
• performance status
• Gender
• baseline hemoglobin level
• Patients who continue to smoke tobacco may be at greater risk of local relapse.
• In some series of HIV-positive patients prognostic factors of poor local tumor
control and survival, and, in some series, of impaired tolerance of RT and
chemotherapy.
• high viral load
• low lymphocyte CD4-positive counts
• AIDS have been prognostic of poor local tumor control and survival, and, in some
series, of impaired tolerance of RT and chemotherapy.

22. Biochemical & Molecular factors
• p53
• in anal carcinoma, p53 is overexpressed with a range of 34% to 100%.
• Wong et al. described that increased p53 expression was associated with
worse local–regional control and DFS
• p21
• lack of p21 expression is associated with poor prognosis in patients with
squamous cell carcinoma of the anal canal (SCCA).
• Holm et al. reported that a lack of p21 expression was associated with
reduced OS
• Nilsson et al. reported that absence of the same p21 expression was also
responsible for an increased LRF rate
• Ki-67, nuclear factor kappa B, 5HH, and Gli-1
Devita Onvology,10th edition

23. Biologic characterstics
• Predominantly a loco-regional disease
• Distant mets relatively rare
• Only 5-10 % will have disease that spreads beyond the pelvis at diagnosis
• As no of metastatically involved LN increase so does the risk of distant
metastasis
• The most common sites of distant metastasis is liver .
• followed by lungs,extrapelvic lymph nodes , skin or bones in that order

24. LN Involvement
• Lymphatic invasion occurs relatively early.
• The overall risk of regional nodal involvement at diagnosis is about 25%.
• Pelvic lymph node metastases were found in as many as 30% of patients treated
by abdominoperineal resection.
• Inguinal metastases were detected clinically in up to approximately 20% of
patients at initial diagnosis and were present subclinically in a further 10% to
20%.
• Nodal metastases were associated with 30% of cancers confined to the sphincter
muscles.
Bilimoria KY, Bentrem DJ, Rock CE, et al. Outcomes and prognostic factors for squamous cell carcinoma of the anal canal: Analysis of patients from the National
Cancer Data Base. Dis Colon Rectum 2009;52:624–631.
Ortholan C, Resbeut M, Hannoun-Levi JM, et al. Anal canal cancer: management of inguinal nodes and benefit of prophylactic inguinal irradiation (CORS-03 study). Int
J Radiat Oncol Biol Phys 2012;82(5):1988–1995.

25. AJCC Staging – Anal Canal Cancers
• The definitions of TNM and the stage groupings have not changed from
the sixth edition.
• The classification applies to carcinomas only; melanomas, carcinoid
tumours, and sarcomas are not included.
American Joint Committee on Cancer • 2010 , AJCC 7th edition

26. T Staging
• T X : Primary tumour cant be assessed
• T 1 : No evidence of primary tumour
• T is : Carcinoma in situ (Bowen's disease, high-grade squamous and anal
intraepithelial lesions)
• T 1 : Tumor 2 cm or less in greatest dimension
• T 2 : Tumor more than 2 cm but not more than 5 cm in greatest dimension
2-5 cm

27. • T 3 : Tumor more than 5 cm in greatest dimension
• T 4 : Tumor of any size that invades adjacent organ(s); e.g., vagina, urethra,
bladder*
• *Direct invasion of the rectal wall, perirectal skin, subcutaneous tissue, or the
sphincter muscle(s) is not classified as T4
>5 cm

28. LN Staging
• N X : regional lymph nodes cannot be assessed
• N 0 : no regional lymph node metastasis
• N 1 : metastasis in perirectal lymph node(s)
• N 2 : metastasis in unilateral internal iliac and/or inguinal
lymph node(s)

29. Contd..
• N 3 : metastasis in perirectal and inguinal lymph nodes and/or
bilateral internal iliac and/or inguinal lymph nodes
• M Staging
• M X : Distant metastasis cant be assessed
• M 0 : No distant metastasis
• M 1 : Distant metastasis

30. LN Involvement
• Lymphatic drainage and nodal involvement of anal cancers depend on the location of the
primary tumor.
• Tumors above the dentate line spread primarily to the anorectal, perirectal, and
paravertebral nodes
• Tumors below the dentate line spread primarily to the superficial inguinal nodes.
• The regional lymph nodes are as follows
• Perirectal
• Anorectal
• Perirectal
• Lateral sacral
• Internal iliac (hypogastric)
• Inguinal
• Superficial
• All other nodal groups represent sites of distant metastasis.

31. Staging

32. Perianal skin/Anal margin tumours
• Primary cancers of the perianal skin are similar to cancers of the skin in other
sites.
• Most are squamous cell cancers,
• Occasionally basal cell cancers and skin adnexal adenocarcinomas.
• Generally well differentiated and keratinizing.
• Grow locally & may extend into anal canal
• The ipsilateral inguinal nodes are the most common site of metastasis and are
involved in from 5% to 20% of cases.
• Extrapelvic metastases are uncommon except in locally advanced cancer or
those with nodal metastases.

33. Perianal Skin Tumour Classification
• T X : Primary tumour cant be assessed
• T 1 : No evidence of primary tumour
• T 1 : Tumor 2 cm or less in greatest dimension
• T 2 : Tumor more than 2 cm but not more than 5 cm in greatest
dimension
• T 3 : Tumor more than 5 cm in greatest dimension
• T 4 : Tumour invades deep extradermal structures ( i.e,
cartilage,skeletal muscle or bone)
• Regional Lymph Nodes
• N X : regional lymph nodes cannot be assessed
• N 0 : no regional lymph node metastasis
• N 1 : metastasis in perirectal lymph node(s)

34. • M Staging
• M 0 : No distant metastasis
• M 1 : Distant metastasis
• Staging

35. Thank You