Epidemiology and classification of anal cancer

Dr Touqeer A Siddiqui

MBBS MD FICM (MRCP) (UK)

Fellow medical oncology

Prince sultan military medical city

INTRODUCTION

• Anal cancer is uncommon. It comprises only 2.5 percent of all digestive system malignancies

• incidence -- increased over the last 30 years, • female gender, • infection with human papillomavirus (HPV), lifetime

number of sexual partners, • genital warts, cigarette smoking, receptive anal

intercourse, and infection with human immunodeficiency virus (HIV).

• Glandular, • Transitional, • Nonkeratinizing squamous

(proximal to distal, respectively). • Distally, the squamous mucosa

(which is devoid of epidermal appendages such as hair follicles, apocrine glands and sweat glands) merges with the perianal skin (true epidermis).

• This mucocutaneous junction has been referred to as the anal "verge" or margin.

Histology of anal cancer

• The anal canal has short zones covered with different types of epithelium from proximal to distal end.

• Rectal zone with colonic type of mucosa • Transitional zone varying with colonic mucosa and

squamous epithelium • Squamous epithelium zone with non-keratinizing

squamous epithelium • Perianal skin with keratinizing squamous cell

epithelium

• Two categories of tumors arise in the anal region.

• Anal canal cancers • Tumors that develop from mucosa (any of the

three types) . • Perianal or anal margin cancers• arise within the skin at or distal to the

squamous mucocutaneous junction

• Carcinoma in the anal canal generally originate from the squamous epithelium in the distal part of the canal, but can also originate from cylindrical epithelium in the colonic mucosa or perianal glands in the transitional zone.

• Most adenocarcinoma in the proximal zone will be designated as distal carcinomas primary in the rectum.

Anal canal tumors

• Squamous cell cancers — Tumors arising in the transitional or squamous mucosa are squamous cell cancers and appear to behave similarly, despite their sometimes variable morphologic appearance

Basaloid features are identified in approximately 25 percent of squamous cell cancers of the anal canal and must be distinguished from basal cell carcinomas of the perianal skin, which as noted below, are classified as skin cancers.

• Basaloid (also termed junctional or cloacogenic) carcinoma is a variant of SCC that arises from epithelial transitional zone.

• Tumors arising within the anal canal above the dentate line are termed nonkeratinizing SCCs, while those arising within the anal canal distal to the dentate line are termed keratinizing SCCs.

• Adenocarcinomas — Adenocarcinomas arising from glandular elements within the anal canal are rare, but appear to share a similar natural history to rectal adenocarcinomas, and are treated similarly

Perianal skin cancers

• Tumors of the perianal skin are most often SCCs but other types of cutaneous malignancies (eg, basal cell carcinoma, melanoma, Bowen's disease, extramammary Paget disease) can arise within this region

Lymphatic drainage

• Lymphatic drainage of anal cancers is dependent upon the anatomic site of origin

• Tumors originating above the dentate line, similar to rectal cancers, drain to the perirectal and paravertebral nodes.

• Tumors arising below the dentate line spread primarily to the superficial inguinal and femoral nodes, areas that are rarely involved by rectal cancer

EPIDEMIOLOGY AND RISK FACTORS

• Sexual activity

• In a population-based, case control study of anal cancer, women with anal cancer were more likely than controls to have a history of genital warts (relative risk [RR] 32.5), herpes simplex 2 (RR 4.1), or chlamydia trachomatis (RR 2.3), while men with anal cancer were more likely than controls to have never been married (RR 8.6), to have engaged in homosexual sexual activity (RR 50), to have practiced receptive anal intercourse (RR 33), and to have a history of genital warts (RR 27) or gonorrhea (RR 17) [36]. Subsequent studies confirmed the relationship between anal cancer and receptive anal intercourse in men

EPIDEMIOLOGY AND RISK FACTORS • Human papillomavirus infection

• Human papillomavirus (HPV) infection is the most commonly diagnosed sexually transmitted disease in the United States and provides as least part of the link between sexual activity and anal cancer.

• A close association exists between infection by oncogenic HPV strains and many premalignant and malignant lesions of the genital tract, anus, and rectum

Furthermore, HPV infection is the common link that explains the association between index and second primary anogenital cancers and oral cavity/pharyngeal cancers

• HPV DNA has been isolated from 46 to 100 percent of in situ and invasive SCCs of the anus , and epidemiologic studies have shown that up to 93 percent of anal SCCs are associated with HPV infection.

• Women are more likely to have HPV associated anal cancer than are men

• HIV infection

• the overall impact of HIV infection on incidence rates of anal cancer remains unclear since population-based studies have produced conflicting results

• The incidence of HPV infection and HPV associated preinvasive and invasive malignancy is increased in HIV-infected patients, regardless of sexual practice

• In a meta-analysis of 53 studies, the prevalence of both high-risk anal HPV subtypes (74 versus 34 percent) and anal cancer (45.9 versus 5.1 per 100,000 men) was significantly higher among HIV-positive as compared to HIV-negative MSM

• Chronic immunosuppression not due to HIV —

• Other causes of chronic immunosuppression, such as solid organ transplantation, also may be associated with the development of high grade AIN and invasive anal carcinoma.

• Among renal transplant recipients, for example, the risk of

anogenital cancer may be increased as much as 100-fold;

• Risk has been associated with persistent HPV infection . AND chronic glucocorticoid therapy

• Cigarette smoking —

• Several case-control studies have noted a statistically significant risk of anal cancer in smokers

• is thought to act as a co-carcinogen

• THANKS