Version July 2025
INTRODUCTION —
Anal cancer is an uncommon disease, with approximately 11,000 new cases diagnosed annually in the United States [1] and over 50,000 cases diagnosed annually worldwide [2]. However, the incidence of anal cancer is increasing globally.
The anatomy, histopathologic classification, epidemiology, and risk factors for anal cancer are presented here. The clinical presentation and diagnosis and the treatment of anal cancer are discussed separately.
●(See "Clinical presentation, diagnosis, and staging of anal cancer".)
●(See "Treatment of anal cancer".)
ANATOMY AND TERMINOLOGY —
The anus is the distal opening of the lower gastrointestinal (GI) tract [3]. The anus consists of the anal canal and the perianal skin within a 5 cm radius of the anal verge. An understanding of the normal anatomy of the anal canal, the perianal skin, and the associated lymphatic drainage is important to the clinical terminology of anal cancer and perianal skin cancer.
Anal canal
●Normal anatomy of the anal canal – The anal canal is approximately 2.5 to 4 cm long, although the actual length varies between individuals. The anal canal is circumferentially surrounded by the internal and external anal sphincter muscles (figure 1) [3]. The anal canal includes mucosa from three different histologic types: glandular, transitional, and squamous epithelium (proximal to distal, respectively).
The anal canal begins superiorly (proximally) where the rectum enters the puborectalis sling at the apex of the anal sphincter complex; on digital rectal examination, this landmark is palpable as the anorectal ring and is approximately 1 to 2 cm proximal to the dentate (pectinate) line.
The dentate line is a macroscopically visible landmark within the anal canal that marks the transition from glandular to squamous mucosa. The transitional zone, a narrow zone of transitional mucosa (which is similar to urothelium), is variably present immediately proximal to the dentate line. The dentate line also divides the anal canal into proximal and distal portions.
The anal canal ends inferiorly (distally) at the anal verge, which corresponds to the introitus of the anal orifice. The anal verge is the junction where the nonkeratinized stratified squamous mucosa within the anal canal (which is devoid of epidermal appendages such as hair follicles, apocrine glands, and sweat glands) eventually merges with the perianal skin (keratinized stratified squamous epithelium or hair-bearing skin). This anal verge is indistinct on macroscopic examination, and anatomically, its location may vary with the patient's body habitus.
●Clinical definition of anal cancer – An anal cancer is clinically defined as a tumor that develops from any of the three types of mucosae located in the anal region (glandular, transitional, and squamous mucosa) and that cannot be visualized in its entirety while gentle traction is placed on the gluteal cheeks (buttocks) (picture 1) [3]. The histologic subtypes of anal cancer are discussed separately. (See 'Anal canal tumors' below.)
Of note, the anatomic site of origin of anal cancer located at the anorectal junction can be difficult to determine. This is because there is no easily identifiable landmark between the rectum and the anus. Additionally, in some individuals, the rectal mucosa may extend to within 1 to 2 cm of the anal verge.
Perianal skin
●Normal anatomy – The perianal skin is defined as skin that is within a 5 cm radius of the anal verge. The perianal skin is "hair-bearing skin" or keratinized stratified squamous epithelium that is characterized by the presence of epidermal appendages (hair follicles, apocrine glands, and sweat glands).
●Clinical definition of perianal skin cancer – Perianal skin cancers are clinically defined as tumors that arise in the hair-bearing skin within a 5 cm radius of the anal verge that can be seen in their entirety with gentle traction placed on the buttocks [3,4]. The histologic subtypes of perianal skin cancer are discussed separately. (See 'Perianal skin cancers' below.)
Lymphatic drainage — Lymphatic drainage of anal canal and perianal cancers is dependent upon the anatomic site of the primary tumor (figure 1) [5-7]. Tumors originating above the dentate line, like rectal cancers, drain to the mesorectal and internal iliac nodes. In contrast, tumors arising below the dentate line may also spread to the superficial inguinal and external iliac (deep inguinal) nodes.
In patients with anal cancer, nodal (N) staging of the lymph nodes is influenced by the anatomic location of the involved lymph nodes (table 1). Further details are discussed separately. (See "Clinical presentation, diagnosis, and staging of anal cancer", section on 'Staging system'.)
HISTOPATHOLOGY —
The histologic types of malignancies that arise within the anus including anal squamous cell carcinomas (SCCs), adenocarcinomas, and neuroendocrine tumors (table 2).
Anal canal tumors — An anal cancer is clinically defined as a tumor that develops from any of the three types of mucosae located in the anal region (glandular, transitional, and squamous mucosa) and cannot be visualized in its entirety while gentle traction is placed on the gluteal cheeks (buttocks) [3]. The histologic subtype of anal cancer is influenced by its location and the tissue type from which it arises within the anal canal.
●Squamous cell carcinoma – Anal SCCs are the most common histologic type of anal carcinoma. Tumors arising within the anal canal above the dentate line (figure 1), including those involving the transition zone, are classified as nonkeratinizing SCCs, whereas those arising distal to the dentate line are classified as keratinizing SCCs. The pathologic classification of tumors arising within the transition zone may be difficult since the transition zone has a widely variable histologic appearance. Nevertheless, anal SCCs, regardless of whether they arise within transitional or squamous mucosa, appear to behave similarly, despite their sometimes variable morphologic appearance [8,9]. By convention, most studies that report outcomes of "anal cancer" refer exclusively to SCCs arising within the mucosa of the anus.
The terms "basaloid features" and "basaloid (junctional or cloacogenic) carcinoma" are no longer used because these tumors are recognized as nonkeratinizing types of SCC. Basaloid features are identified in approximately 25 percent of anal canal SCCs and must be distinguished from basal cell carcinomas of the perianal skin, which are classified as skin cancers. Basaloid carcinoma was a term previously used to describe a variant of SCC arising from the transitional zone. (See 'Perianal skin cancers' below.)
Of note, primary rectal SCCs, which are very rare, can be difficult to distinguish from anal cancer. These tumors are generally treated according to the same approach as anal SCCs. (See "Treatment of anal cancer", section on 'Rectal squamous cell cancers'.)
●Adenocarcinomas – Adenocarcinomas are rare anal canal tumors that arise from glandular elements within the anal canal. These tumors are treated similarly to rectal adenocarcinomas since they share a similar natural history. (See "Treatment of anal cancer", section on 'Anal adenocarcinoma'.)
●Neuroendocrine tumors – Neuroendocrine tumors of the anal canal are a rare and aggressive malignancy [10]. These tumors are classified and managed using the principles of other neuroendocrine neoplasms. The pathology of neuroendocrine tumors of the anus is discussed separately. (See "Pathology and classification of gastroenteropancreatic neuroendocrine neoplasms".)
Perianal skin cancers — Perianal skin cancers are defined as tumors that arise in the hair-bearing skin within a 5 cm radius of the anal verge that can be seen in their entirety with gentle traction placed on the buttocks [3,4]. These rare tumors behave biologically like skin cancers and, with the exception of melanoma, are staged (table 1) and treated similarly to anal cancers. (See "Clinical presentation, diagnosis, and staging of anal cancer", section on 'Postdiagnostic evaluation' and "Treatment of anal cancer", section on 'True perianal skin cancers'.)
Perianal skin cancers can present as the following histologies:
●SCC – Invasive SCC is the most common tumor found in the perianal skin. The pathology of invasive cutaneous SCC is discussed separately. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis", section on 'Invasive cutaneous squamous cell carcinoma'.)
●Basal cell carcinoma – Perianal basal cell carcinoma is quite rare [11]. The pathology of basal cell carcinoma is discussed separately. (See "Basal cell carcinoma: Epidemiology, pathogenesis, clinical features, and diagnosis", section on 'Pathology'.)
●SCC in situ – SCC in situ (Bowen disease) can rarely occur within the perianal skin as it can in other areas of non-sun-exposed skin. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis", section on 'Cutaneous squamous cell carcinoma in situ'.)
●Melanoma – Malignant melanoma can arise in either the anal canal or perianal skin. Anal and perianal melanoma should be staged and treated using the same approach as melanoma at other sites. (See "Staging work-up and surveillance of cutaneous melanoma" and "Surgical management of primary cutaneous melanoma or melanoma at other unusual sites".)
●Paget disease of the anus – Paget disease of the anus, an intraepithelial adenocarcinoma, can rarely be found in the perianal skin. Paget disease of the anus can be one of two types: a primary cutaneous malignancy, in which the tumor cells show sweat gland differentiation, and a lesion, in which there is involvement of adjacent squamous epithelium by lateral intramucosal/intraepithelial spread from an underlying adenocarcinoma of the rectum or perianal glands.
EPIDEMIOLOGY —
Although anal cancer is an uncommon disease, its incidence is increasing in the United States as well as other countries [12-16].
The incidence and mortality of anal cancer is accelerating in the United States, and it may surpass cervical cancer to become the leading human papillomavirus (HPV)-associated cancer in older adult females. In observational data from the United States Cancer Statistics dataset, incidence rates (IR) for anal squamous cell carcinoma (SCC) increased 2.7 percent per year between 2001 and 2015 [17]. From 2001 to 2019, the most pronounced age-adjusted increases for HPV-associated anal SCC were in females between the ages of 60 and 69 (7.1 cases per 100,000), followed by individuals older than 70 years (6.5 cases per 100,000). In contrast, between 2007 and 2019, IR declined in females between the ages of 40 and 44 years old, as well as males.
Another observational study from the United States evaluated the impact of geographic variation on anal cancer incidence between 2014 to 2018 compared with 2001 to 2005 [12]. In this study, an increase in anal SCC was noted for those older than 50 years old specifically in the Midwestern and Southeastern United States, with a correlation for males with state-level acquired immunodeficiency syndrome (AIDS) prevalence patterns. In contrast, for females, the rise in anal cancer incidence may be associated with tobacco use. Other international observational studies suggest that the incidence of HPV-associated anal SCC in females is the highest in resource-limited countries [13].
The stage distribution and mortality rates for anal cancer have also changed. In an observational study from the United States between 2001 and 2015, the incidence of distant-stage disease tripled (annual percentage change in males and females of 8.6 and 7.5 percent, respectively), and the incidence of regional (nodal [N])-stage disease doubled [14]. Anal cancer mortality also increased over this same time (3.1 percent increase per year), particularly among individuals ages 50 and older.
There is an especially high incidence of anal cancer in certain populations, such as men who have sex with men (MSM) and people living with human immunodeficiency virus (HIV). Further details are discussed separately. (See 'Sexual activity and sexually transmitted infections' below and 'HIV infection' below.)
In contrast to other common malignancies affecting HIV positive individuals (eg, Kaposi sarcoma and non-Hodgkin lymphoma), the incidence of anal cancer has not declined in the era of potent antiretroviral therapy [18,19]. (See "HIV infection and malignancy: Management considerations".)
RISK FACTORS —
Risk factors for the development of anal cancer include human papillomavirus (HPV) infection, HIV infection, lifetime number of sexual partners, receptive anal intercourse, genital warts, and cigarette smoking. From an etiologic standpoint, anal cancer is more similar to genital malignancies than it is to gastrointestinal (GI) tract malignancies.
Certain populations are also known to be at higher-than-average risk for anal cancer. These include people living with HIV (PLWH), men who have sex with men (MSM), females diagnosed with HPV-related gynecologic precursor lesions or cancer, and individuals with chronic immunosuppression.
Sexual activity and sexually transmitted infections — The association between sexual activity and the development of anal cancer has been demonstrated based on data in MSM [20,21] as well as heterosexual individuals [22]. Sexual risk factors that have been identified for anal cancer include receptive anal intercourse [22-28], multiple lifetime sexual partners [22], and sexually transmitted infections (STIs). While HPV and HIV are the STIs most frequently associated with anal cancer, other STIs that have also been observed include anal or genital warts, herpes simplex virus 2 (HSV-2), chlamydia trachomatis, gonorrhea, and syphilis [22,23].
MSM are at a high risk of developing anal cancer [29-31]. The incidence of anal cancer is highest among MSM who are living with HIV (MSMLWH) [29,31,32], which also increases over time [29]. However, MSM who are living without HIV are also still at risk for developing anal cancer. (See 'HIV infection' below.)
As examples:
●In a meta-analysis of anal cancer incidence by risk group, the summary incidence rates (IR; cases per 100,000 person-years) for anal cancer were higher for MSM living with HIV (n = 7 studies, 2,229,234 person-years, IR 85, 95% CI 82-89) but still elevated for MSM living without HIV (n = 2 studies, 48,135 person-years, IR 19, 95% CI 10-36) [31]. Similarly, in a cohort study from the HIV/AIDS Cancer Match Study, the greatest absolute risk factor for anal cancer was in MSM living with HIV [29].
●In the HIV/AIDS Cancer Match Study, among MSM younger than 30 years of age, the cumulative incidence of anal cancer was three times higher between 10 to 20 years following the diagnosis of AIDS relative to the first 10 years following diagnosis of AIDS (1.23 versus 0.35 percent) [29].
Human papillomavirus infection — HPV infection is the most frequently diagnosed STI in the United States and provides at 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 [22,33]. Furthermore, HPV infection is the common link that explains the association between index and second primary anogenital cancers and oral cavity/pharyngeal cancers. (See "Virology of human papillomavirus infections and the link to cancer" and "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer", section on 'Epidemiology' and "Second primary malignancies in patients with head and neck cancers", section on 'Incidence'.)
HPV deoxyribonucleic acid (DNA) has been isolated from 46 to 100 percent of in situ and invasive squamous cell carcinomas (SCCs) of the anus [22,34-36], and epidemiologic studies have shown that up to 93 percent of anal SCCs are associated with HPV infection. Females are more likely to have HPV associated anal cancer than are males [37]. HPV 16 presence is also associated with a better prognosis [38].
While several HPV types can be found in the anogenital tract, only a few have been associated with cancer. The spectrum of HPV types in the anal canal is similar to that described in the cervix and is associated with the same "risk" phenotypes. As in cervical cancer, HPV 16 is the most frequently isolated type in anal malignancies [22,36,39,40], and its presence predicts for preinvasive as well as invasive cancer. HPV 16 associated anal SCC can be identified histologically by immunohistochemical expression of p16 [38]. In contrast, low-grade in situ lesions frequently are associated with other HPV subtypes [28,40,41].
The premalignant condition of cervical intraepithelial neoplasia (CIN or squamous intraepithelial lesions [SIL]) associated with HPV infection of the cervix also occurs with HPV infections involving the anus (termed anal SIL, previously called anal intraepithelial neoplasia [AIN]). Both cervical SIL and anal SIL can be morphologically low grade or high grade. The terminology associated with anal squamous dysplasia is discussed in detail separately. (See "Anal squamous intraepithelial lesions: Epidemiology, clinical presentation, diagnosis, screening, prevention, and treatment", section on 'Histopathology and nomenclature'.)
HPV infection in the anal canal and perianal region may be subclinical or clinically apparent as condylomata. SIL, particularly high-grade SIL, is thought to be the precursor of anal cancer. Progression of high-grade SIL to invasive anal SCC is related to many factors, including HIV seropositivity, a lower cluster of differentiation 4 (CD4) count, the type of HPV infection, and higher levels of DNA of high-risk HPV types in the anal canal [42]. (See "Anal squamous intraepithelial lesions: Epidemiology, clinical presentation, diagnosis, screening, prevention, and treatment", section on 'Natural history'.)
The prevalence of HPV infection in MSM, a group at high risk for both high-grade SIL and invasive anal cancer, is higher in the presence of HIV infection [30]. (See 'HIV infection' below and 'Sexual activity and sexually transmitted infections' above.)
A minority of anal cancers are not associated with HPV infection. Among female patients with anal cancer, no difference in prognosis has been noted between HPV-positive and HPV-negative tumors; but in male patients, HPV-positive tumors are associated with improved overall survival [43]. For locally advanced tumors treated with chemoradiation, HPV-negative tumors with a p53 mutation demonstrated reduced locoregional control and worsened overall survival [44].
Studies are evaluating the utility of HPV vaccines in preventing cervical and anal neoplasia in females and anal lesions in males [45-47]. This 9-valent HPV vaccine targets HPV types 6, 11, 16, and 18 as well as types 31, 33, 45, 52, and 58. Further details of the efficacy of these vaccines in preventing anal disease are discussed separately. (See "Human papillomavirus vaccination", section on 'Anal disease' and "Anal squamous intraepithelial lesions: Epidemiology, clinical presentation, diagnosis, screening, prevention, and treatment", section on 'Prevention'.)
HIV infection — Data are unclear as to the impact of HIV infection on the development of anal cancer. Some studies suggest that HIV or AIDS is strongly associated with the development of anal cancer. In contrast, other studies suggest that anal cancer in PLWH may be mediated through other known risk factors, such as HPV infection, receptive anal intercourse, chronic immunosuppression, or advancing age.
Data supporting an association between HIV and increased incidence of anal cancer include the following:
●The increasing rates of anal cancer in the United States are influenced by HIV infection in males but are independent of HIV infection in females [48,49]. In an analysis of the HIV/AIDS Cancer Match study between 2001 and 2015, among 16,110 cases of anal SCC (6277 in males and 9833 in females), 14.5 percent of all cases occurred in PLWH [49]. In 2013 to 2015, 33 percent of anal cancers among males occurred in PLWH, but only 3 percent occurred among females. The prevalence of anal SCCs among males living with HIV (MLWH) increased between 2001 and 2015 (29.1 versus 34 percent) but remained stable for females living with HIV (2.6 versus 2.3 percent).
●In an observational series of patients living with AIDS and cancer, the relative risk (RR) of developing anal cancer in PLWH was much higher than that in the general population (standardized incidence ratio 19.1, 95% CI 18.1-20) [50]. The incidence of anal cancer was highest among MSM with increased age and in those with AIDS.
The incidence of SIL and anal cancer is higher in MLWH, particularly MSMLWH [30-32,51-54]. For patients older than 35 years living with HIV, treating high-grade anal SIL reduced the risk of invasive anal cancer in a phase III trial (ANCHOR) [55]. Further details of this trial are discussed separately. (See "Anal squamous intraepithelial lesions: Epidemiology, clinical presentation, diagnosis, screening, prevention, and treatment", section on 'Risk of progression to anal cancer'.)
●In a meta-analysis of anal cancer incidence by risk group, the summary IR (cases per 100,000 person-years) for anal cancer were higher for MSMLWH (n = 7 studies, 2,229,234 person-years, IR 85, 95% CI 82-89) compared with MLWH who did not engage in sex with men (n = 5 studies, 1,626,448 person-years, IR 32, 95% CI 30-35) [31].
●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 MSMLWH as compared with MSM without HIV [30].
Other studies have produced conflicting results regarding the impact of HIV infection on the development of anal cancer [48,56-60].
●An increased incidence of anal cancer was noted in some reports during the peak of the AIDS epidemic [59]. In New York City, for example, there was a 10-fold increase in the incidence of anal cancer among males aged 20 to 49 from 1979 to 1985, concurrent with the onset of the AIDS epidemic and a marked rise in Kaposi sarcoma and non-Hodgkin lymphoma in this population [59]. In contrast, case-control studies of single males living in San Francisco did not find a significant rise in the incidence of anal cancer from before the appearance of AIDS in about 1980 to the late 1980s, a period in which there was an increased incidence of both Kaposi sarcoma and non-Hodgkin lymphoma [27,61,62]. (See "HIV infection and malignancy: Management considerations" and "HIV infection and malignancy: Epidemiology and pathogenesis".)
●PLWH who have a longer duration of HIV infection have a substantially higher rate of anal cancer. However, in contrast to other AIDS-associated cancers, the use of potent antiretroviral therapy has not led to a decline in the incidence of anal cancer [18,63].
It is possible that HIV infection interacts with HPV to predispose PLWH to anal cancer. The incidence of HPV infection and HPV associated preinvasive and invasive malignancy is higher in PLWH, regardless of sexual practice [28,64-68]. Infection with multiple types of anal HPV is also more common in MSMLWH and is associated with significant immunosuppression (CD4 count below 200/microL) [69]. This finding could reflect increased HPV replication in patients with AIDS, allowing more HPV types to reach a detectable concentration. Infection with more than one type of HPV is associated with an increased risk of abnormal anal cytology [51,70]. (See "Virology of human papillomavirus infections and the link to cancer".)
Chronic immunosuppression in HIV infection is also associated with a higher risk of anal cancer and of progression from low-grade SIL to high-grade SIL or invasive cancer [28,42,71]. As an example, within a nested case-control study in the Swiss HIV cohort study, low CD4 counts were associated with anal cancer, both at nadir and at the time of cancer diagnosis [71]. The influence of CD4 counts appeared to be strongest six to seven years prior to the diagnosis of anal cancer (odds ratio for <200 versus ≥500 cells/microL 14, 95% CI 3.85-50.9).
As the median age of PLWH continues to increase [72], studies suggest an increased risk of anal cancer in the older adult population living with HIV [29,73]. In a case-cohort study of PLWH older than age 65 years, HIV was associated with an increased incidence of anal cancer (adjusted hazard ratio of 34.2) [73].
Chronic immunosuppression
Solid organ transplant recipients — In patients who undergo solid organ transplantation, chronic immunosuppression from immunosuppressive agents also may be associated with the development of high-grade SIL and invasive anal carcinoma [31,74-76].
●In a meta-analysis of anal cancer incidence by risk group, the summary IR (cases per 100,000 person-years) was 13 (95% CI 12-15) for anal cancer among solid organ transplant recipients (n = 5 studies, 1,946,206 person-years) [31]. By 10 years post-transplant, this IR reached 24.5 for males and 49.6 for females.
●Among kidney transplant recipients, the risk of anogenital cancer may be increased as much as 100-fold; this high risk level has been associated with persistent HPV infection [75,76].
Further details on malignancy after solid organ transplantation are discussed separately. (See "Malignancy after solid organ transplantation".)
Other immunocompromised patients — Autoimmune disease also is a risk factor for subsequent anal cancer, in part related to treatment with chronic glucocorticoids [77,78]. In a meta-analysis of anal cancer incidence by risk group, the summary IR (cases per 100,000 person-years) for anal cancer among individuals with systemic lupus erythematosus was 10 (95% CI 5-19), for ulcerative colitis it was 6 (95% CI 3-11), and for Crohn disease it was 3 (95% CI 2-4). (See "Major adverse effects of systemic glucocorticoids".)
Cigarette smoking — Several case-control studies have noted an increased risk of anal cancer in smokers, especially current smokers [24,36,71,79-82]. In one series, cigarette smoking was associated with an increased risk of anal cancer (RR 1.9 for 20 pack-years, RR 5.2 for 50 pack-years) [24]. Cigarette smoking is highly associated with cervical neoplasia and is thought to act as a cocarcinogen for anogenital SCC [83]. (See "Cervical cancer screening tests: Techniques for cervical cytology and human papillomavirus testing".)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anal cancer".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Anal cancer (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Epidemiology – Although anal cancer is an uncommon disease, its incidence is increasing globally. (See 'Epidemiology' above.)
●Clinical terminology – The anus, the distal opening of the lower gastrointestinal (GI) tract, consists of the anal canal and the perianal skin within a 5 cm radius of the anal verge (figure 1). (See 'Anatomy and terminology' above.)
•Anal cancer – An anal cancer is clinically defined as a tumor that develops from any of the three types of mucosae located in the anal region (glandular, transitional, and squamous mucosa) and cannot be visualized in its entirety while gentle traction is placed on the gluteal cheeks (buttocks). (See 'Anal canal' above.)
•Perianal skin cancer – Perianal skin cancers are clinically defined as tumors that arise in the hair-bearing skin within a 5 cm radius of the anal verge that can be seen in their entirety with gentle traction placed on the buttocks. (See 'Perianal skin' above.)
●Histopathology – The histologic types of anal cancer including anal squamous cell carcinomas (SCCs), adenocarcinomas, and neuroendocrine tumors (table 2). (See 'Anal canal tumors' above.)
Perianal skin cancers present mostly as SCCs, but can also include basal cell carcinoma, SCC in situ, melanoma, and Paget disease of the anus. (See 'Perianal skin cancers' above.)
●Risk factors – Risk factors for the development of anal cancer include human papillomavirus (HPV) infection, HIV infection, lifetime number of sexual partners, receptive anal intercourse, genital warts, and cigarette smoking. Certain populations at higher-than-average risk for anal cancer include people living with HIV (PLWH), men who have sex with men (MSM), females diagnosed with HPV-related gynecologic precursor lesions or cancer, and individuals with chronic immunosuppression. (See 'Risk factors' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges David P Ryan, MD, who contributed to earlier versions of this topic review.
