Classification and epidemiology of anal cancer

Authors
David P Ryan, MD
Christopher G Willett, MD
Section Editor
Richard M Goldberg, MD
Deputy Editor
Diane MF Savarese, MD
Disclosures: David P Ryan, MD Nothing to disclose. Christopher G Willett, MD Nothing to disclose. Richard M
Goldberg, MD Grant/Research/Clinical Trial Support: Sanofi [Colon cancer (Afibercept)]; Bayer [Colon cancer
(Regorafinib)]; Medimmune [Colon cancer (Experimental agent)]; Merck [Colon cancer (PD-1 inhibitor MK-3475)];
Kanghong [Colon cancer (Experimental drug)]; Biothera [Colon cancer (Data Safety Monitoring Committee Chair for a
phase III trial)]; Baxter [Colon cancer (Experimental drug)]; Taiho [Colon cancer (Experimental drug)]; Lilly [Colon
cancer (Ramicurimab)]. Diane MF Savarese, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed
by vetting through a multi-level review process, and through requirements for references to be provided to support the
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All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jun 2015. | This topic last updated: Jan 18, 2015.
INTRODUCTION Anal cancer is uncommon. It comprises only 2.5 percent of all digestive system
malignancies in the United States; only 7270 new cases are diagnosed annually [1].
The incidence of anal cancer in the general population has increased over the last 30 years, both in
the United States and elsewhere [2-6]. An increased incidence has been associated with 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) [7]. Thus, from an etiologic standpoint, anal cancer is more similar to genital
malignancies than it is to gastrointestinal tract cancers.
Substantial progress has been made in the pathophysiology and treatment of anal cancer [8]. In the
1960s, this malignancy was thought to be due to chronic perianal inflammation and was treated
routinely by abdominoperineal resection, necessitating a permanent colostomy [9]. As a result of
carefully conducted epidemiologic and clinical studies, it is now known that anal cancer is
associated with HPV infection and that cure of anal cancer is possible in the majority of patients
with preservation of the anal sphincter.
The pathology and epidemiology of anal cancer will be reviewed here. The clinical features,
diagnosis, and treatment are discussed separately. (See "Clinical features, staging, and treatment
of anal cancer".)
ANATOMY AND HISTOLOGY The proximal end of the anal canal begins anatomically where the
rectum enters the puborectalis sling at the apex of the anal sphincter complex (palpable as the
anorectal ring on digital rectal examination, and approximately 1 to 2 cm above the dentate line); it
extends distally to the point where the squamous mucosa blends with the perianal skin, which
roughly coincides with the palpable intersphincteric groove or the outermost boundary of the internal
sphincter muscle, a distance of approximately 4 cm (figure 1) [10]. The anal canal is divided by the

dentate line, a macroscopically visible landmark that overlies the transition from glandular to
squamous mucosa; immediately proximal to the dentate line, a narrow zone of transitional mucosa
that is similar to urothelium is variably present.
The proximal region of the anus encompasses mucosa of three different histologic types: glandular,
transitional, and 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. This boundary is indistinct on macroscopic
examination, and, anatomically, its location may vary with the patient's body habitus.
As a result, four distinct categories of tumors arise in the anal region:
Tumors that develop from any of the three types of mucosa lining the anal canal are termed
anal canal cancers. Tumors arising in the transitional or squamous mucosa are squamous cell
cancers (SCCs) and appear to behave similarly, despite their sometimes variable morphologic
appearance. By convention, most series that report outcomes of anal cancer refer
exclusively to these tumors.
Adenocarcinomas arising from glandular elements within the anal canal are rare but appear
to share a similar natural history to rectal adenocarcinomas; they are treated similarly.
(See "Clinical features, staging, and treatment of anal cancer", section on 'Treatment of
localized adenocarcinoma of the anal canal'.)
Tumors arising within the hair-bearing skin at or distal to the squamous mucocutaneous
junction have been referred to as anal margin cancers. However, the preferred term is perianal
skin cancers. (See "Clinical features, staging, and treatment of anal cancer", section on
'Staging' and "Clinical features, staging, and treatment of anal cancer", section on 'Treatment
of perianal skin cancers'.)
Primary rectal SCCs, which are very rare, can be difficult to distinguish from anal cancers,
and they should be treated according to the same approach as anal cancer. (See "Clinical
features, staging, and treatment of anal cancer", section on 'Rectal squamous cell cancers'.)
Histology Several histologic types of malignancy arise within the anus, including SCC, which is
most common; adenocarcinoma; melanoma; and, rarely, sarcoma (table 1) [11]. Due to the variation
in anatomy (particularly the transition zone), the anal canal can be quite short in length in some
individuals, and the anatomical location as determined by a surgeon or endoscopist should not
determine the classification of a tumor. Rather, the histology and location of tumors in the anal
region guide the appropriate diagnosis and treatment.
Anal canal tumors There is no easily identifiable landmark between the rectum and the anus; in
addition, the transition zone has a widely variable histologic appearance. As a result, the pathologic
classification of tumors arising in this area may be difficult.
Squamous cell cancers Tumors arising in the transitional or squamous mucosa are SCCs
and appear to behave similarly, despite their sometimes variable morphologic appearance
[12,13]. By convention, most series that report outcomes of anal cancer refer exclusively to
these tumors. The term anal cancer by common definition refers to SCCs arising within the
mucosa of the anus, and the two terms will be used interchangeably throughout this review.

Basaloid features are identified in approximately 25 percent of SCCs 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. However, these terms have largely
been abandoned because these tumors are now recognized as nonkeratinizing types of SCC.
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.
Determination of the anatomic site of origin of carcinomas that overlap the anorectal junction can be
problematic. For staging purposes, such tumors are classified as rectal cancers if their epicenter is
located more than 2 cm proximal to the dentate line or proximal to the anorectal ring on digital
examination, and as anal canal cancers if their epicenter is 2 cm or less from the dentate line [10].
Perianal skin cancers The clinical distinction between tumors of the anal canal and those that
involve the anal margin or perianal skin can also be difficult. As noted above, SCCs that arise on
any mucosal surface of the anus are treated as anal canal cancers, even if they are located distally
at the perianal margin. In contrast, tumors arising within the hair-bearing skin at or distal to the
squamous mucocutaneous junction have been termed anal margin cancers. However, the preferred
term is perianal skin cancers since, with the exception of melanomas, tumors arising within the
perianal skin behave biologically like skin cancers. Although there are essentially no prospective
data validating this practice, these tumors are classified and staged (table 2) as skin cancers rather
than anal canal cancers [14]. However, the regional nodal drainage (relevant to the N category) is
specific to this anatomic site (table 3) [10].
Most clinicians treat SCC lesions of the perianal skin as anal canal cancers using radiation therapy
(RT) and concurrent chemotherapy. Local treatment, surgery, or local RT (electrons) is used only
when the lesion is very separate from the anal verge and is a discrete skin lesion. However, it can
be very difficult to distinguish between tumors arising on the hair-bearing skin or within
the anus/anal cancer. In practice, the distinction between perianal skin cancers and
anal canal/margin cancers is difficult, and the default management by most clinicians is to assume
that these are anal margin/canal cancers if there is any doubt, and to treat with initial
chemoradiotherapy. Notably, cooperative group trials do not make a distinction between anal
margin and anal canal SCCs in terms of eligibility.
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.
Bowen's disease (SCC in situ) can occur within the perianal skin as it can in other areas of
non sun-exposed skin. (See "Clinical features and diagnosis of cutaneous squamous cell
carcinoma (SCC)".)
Melanomas that arise in either the anal canal or perianal skin should be treated according to
the same principles commonly applied to this tumor at other sites. (See"Initial surgical
management of melanoma of the skin and unusual sites".)

Paget disease of the anus, an intraepithelial adenocarcinoma, 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.
Lymphatic drainage Lymphatic drainage of anal cancers is dependent upon the anatomic site of
origin [15-17]. Tumors originating above the dentate line, similar to rectal cancers, drain to the
perirectal and paravertebral nodes. In contrast, 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 Although it remains an uncommon cancer, the
incidence of anal cancer is increasing in the United States and other countries [2,18-20]. In data
from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer
Institute, between 1973 to 1996 and 1997 to 2009, United States incidence rates for anal squamous
cell cancer (SCC) increased threefold in men (from 1 to 3 per 100,000 person-years) and 1.7-fold in
women (from 1.4 to 2.4 per 100,000 person-years) [21].
In certain populations, such as men who have sex with other men (MSM) and human
immunodeficiency virus (HIV)-infected patients, there is an especially high incidence of anal cancer.
The rate of anal cancer was estimated to be as high as 37 per 100,000 among MSM prior to the
HIV epidemic [22], rendering its incidence in this population similar to that of cervical cancer in
women prior to the introduction of cervical Papanicolaou (Pap) smear screening [13]. The incidence
of anal cancer among HIV-positive MSM has been estimated to be approximately twice that of HIVnegative MSM [23,24].
In contrast to other common malignancies affecting HIV-positive individuals (eg, Kaposi's sarcoma
and non-Hodgkin lymphoma), the incidence of anal cancer has not declined in incidence in the era
of potent antiretroviral therapy (formerly referred to as highly active antiretroviral therapy [HAART])
[25,26]. This was demonstrated in a study in San Francisco County, in which the age-adjusted
incidence of anal cancer in men aged 40 to 64 years of age (regardless of sexual orientation) more
than quadrupled from the pre-HIV period (1973 to 1978) to the present era (1996 to 1999), following
the widespread availability of potent antiretroviral therapy [27]. (See "HIV infection and malignancy:
Management considerations".)
Risk factors In the past, anal cancer was thought to develop in areas of chronic local
inflammation or irritation associated with benign anal and perianal conditions such as hemorrhoids,
fissures, and fistulae [28,29]. Case reports of anal cancer developing in the setting of inflammatory
bowel disease (IBD) led to the conclusion that this tumor resulted from chronic inflammation, in a
manner similar to the development of colorectal neoplasia in patients with underlying IBD [30,31].
(See "Colorectal cancer surveillance in inflammatory bowel disease".)
However, subsequent case-control studies found little to no impact of a history of hemorrhoids,
fistulae, and fissures on the development of anal cancer [32,33]. Furthermore, in a large Danish
series, none of the 1160 patients with IBD developed anal cancer [34].

Sexual activity Initial reports suggesting an increased incidence of the disease in homosexual
men provided a link between sexual activity and the development of anal cancer [22,35]. This
relationship has been confirmed in subsequent reports, as illustrated by the following observations:
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 [32,33,37-39].
A second case-control study in heterosexuals compared 417 patients with anal cancer, 534
patients with rectal cancer, and 554 normal controls [40]. In multivariate analysis, the strongest
risk factors for anal cancer in women were 10 or more lifetime sexual partners (RR 4.5) and a
history of anal warts (RR 11.7), genital warts (RR 4.6), gonorrhea (RR 3.3), cervical dysplasia
(RR 2.3), or sexual partners with a history of a sexually transmitted disease (RR 2.4). A history
of engaging in receptive anal intercourse before the age of 30 and at least two anal
intercourse partners were also significant risk factors in women. Among heterosexual men,
multivariate analysis revealed significantly elevated risks of anal cancer with 10 or more
lifetime sexual partners (RR 2.5), a history of anal warts (RR 4.9), or a history of syphilis or
hepatitis (RR 4.0).
Anal cancer and cervical cancer in women Further support for the role of sexual activity in
the development of anal cancers derives from reports demonstrating a strong relationship
between cervical cancer and anal cancer in women [41-44]. In data from the Danish Cancer
Registry, the odds ratio for developing anal cancer following a diagnosis of cervical cancer
was significantly higher than the risk of developing either stomach or colon cancer [42]. In
addition, women with anal cancer had a greater likelihood of prior vulvar, vaginal, or cervical
cancers [43].
In the SEER database in the United States, the RR of developing anal or vaginal cancer
following a diagnosis of invasive cervical cancer were 4.6 and 5.6, respectively [44].
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
[40,45]. 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 "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 DNA has been isolated from 46 to 100 percent of in situ and invasive SCCs of the anus [40,4648], 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 [49].
HPV16 presence is also associated with a worse prognosis [50].

While a number of 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 [40,48,51,52], and its presence predicts for preinvasive
as well as invasive cancer. In contrast, low grade in situ lesions frequently are associated with other
HPV subtypes [39,52,53].
The premalignant condition of cervical intraepithelial neoplasia associated with HPV infection (CIN
or squamous intraepithelial lesions) also occurs with HPV infections involving the anus (termed anal
intraepithelial neoplasia [AIN], also known as anal squamous intraepithelial lesions [ASIL]). As in
CIN, AIN can be morphologically low grade or high grade. (See "Anal squamous intraepithelial
lesions: Diagnosis, screening, prevention, and treatment".)
HPV infection in the anal canal and perianal region may be subclinical, or clinically apparent as
condylomata. AIN, particularly high-grade AIN, is considered to be the precursor of anal cancer.
Progression of AIN to invasive anal SCC is related to many factors, including HIV seropositivity, a
lower CD4 count, the type of HPV infection, and higher levels of DNA of high-risk HPV types in the
anal canal [54].
The prevalence of HPV infection in MSM, a group at high risk for both AIN and invasive anal cancer,
is higher in the presence of HIV infection [55]. (See 'HIV infection'below.).
A substantial minority of anal cancers are not associated with HPV infection. No difference has
been noted between HPV positive and HPV negative tumors in regards to patient age, the presence
of adjacent dysplasia, ductal differentiation, or prognosis [56].
Vaccines directed against the HPV types associated with cervical and anal neoplasia in women and
anal lesions in males have been developed, and their utility for prevention of anal neoplasia is
beginning to be studied. As an example, in a randomized trial involving 4065 males, a quadrivalent
HPV vaccine was effective in preventing infection with HPV types 6, 11, 16, and 18 and preventing
the development of external genital lesions. (See "Clinical trials of human papillomavirus vaccines",
section on 'Clinical trials of HPV vaccine in males'.)
In a planned substudy of that trial evaluating the impact of the quadrivalent vaccine on the
development of AIN in 602 MSM, there was a 78 percent decrease in the incidence of AIN
associated with HPV types 6, 11, 16, and 18 among men who received all three vaccine doses
compared with placebo [57]. The results of this trial and recommendations for the use of HPV
vaccines are discussed separately. (See "Anal squamous intraepithelial lesions: Diagnosis,
screening, prevention, and treatment", section on 'Prevention' and "Recommendations for the use
of human papillomavirus vaccines".)
HIV infection It is unclear whether HIV infection itself has a direct effect on the development of
anal cancer or if this is mediated through HPV. The data supporting a relationship between HIV,
HPV, and anal cancer include the following observations:
Epidemiologic data indicate that the increasing anal cancer rates in the United States
between 1980 and 2005 were strongly influenced by the HIV epidemic in males but were
independent of HIV infection in females [19]. Among men, the incidence rates increased by 3.4
percent annually overall and by 1.7 percent annually in men without HIV infection. Among

women, incidence rates of anal cancer increased 3.3 percent annually overall and by 3.3
percent annually in those without HIV infection.
There is a markedly higher incidence of AIN and anal cancer in HIV-infected men, particularly
MSM [55,58-61]. In a report of data from 13 cohorts (11 clinic-based, including 34,189 HIVinfected and 114,260 HIV-uninfected individuals) that were included in the North American
AIDS Cohort Collaboration on Research and Design (NA-ACCORD) for the years 1996 to
2007, the unadjusted anal cancer incidence rates per 100,000 person-years were 131 for HIVinfected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men [61].
The incidence of HPV infection and HPV associated preinvasive and invasive malignancy is
increased in HIV-infected patients, regardless of sexual practice [39,62-66].
Among HPV infected individuals, the prevalence of high grade AIN and anal carcinoma is
higher in those with concomitant HIV infection compared with those who are HIV-negative [67].
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 with HIV-negative MSM [55].
Despite these observations, the overall impact of HIV infection on incidence rates of anal cancer
remains unclear since population-based studies have produced conflicting results
[4,19,23,24,68,69]. The following observations illustrate the range of findings:
An increased incidence of anal cancer was noted in some reports during the peak of the
AIDS epidemic [68]. In New York City, for example, there was a 10-fold increase in the
incidence of anal cancer among men aged 20 to 49 from 1979 to 1985, concurrent with the
onset of the AIDS epidemic and a marked rise in Kaposi's sarcoma and non-Hodgkin
lymphoma in this population [68]. In contrast, case-control studies of single men 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's sarcoma and non-Hodgkin lymphoma [38,70,71]. (See "HIV
infection and malignancy: Management considerations" and "HIV infection and malignancy:
Epidemiology and pathogenesis".)
In an American series linking registries reporting both AIDS and cancer, the RR of developing
anal cancer at and after the diagnosis of AIDS was 84 (95% CI 46.4-152) among homosexual
patients compared with the general population and 38 (95% CI 9.4-151) among nonhomosexual patients [23]. However, a second report that linked cancer and AIDS registries
across both the United States and Puerto Rico noted only a nonsignificant trend toward an
increased risk of anal cancer with the acquisition of AIDS [24].
Patients with a longer duration of HIV infection have a substantially higher rate of anal
cancer, but 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 [72,73].
Without controlling for receptive anal intercourse and prior HPV infection, it is difficult to discern the
true effect of HIV on the incidence of anal cancer. It is possible that HIV infection interacts with HPV
to predispose to anal cancer. In a cohort of 346 HIV-infected and 262 HIV-negative homosexual
men, infection with multiple anal HPV types was more common in the HIV-infected patients (73
versus 23 percent) and was associated with significant immunosuppression (CD4 count
below 200/microL) [74]. This finding could reflect increased HPV replication in patients with AIDS,

which would allow 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 [58,75].
(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 AIN to high-grade AIN or invasive cancer [39,54,76]. As an example,
within a nested case-control study in the Swiss HIV cohort study, low CD4 counts were significantly
associated with anal cancer, both at nadir and at the time of cancer diagnosis [76]. 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 14.0, 95% CI 3.85-50.9).
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 [77]. Among renal transplant recipients, for example, the risk of
anogenital cancer may be increased as much as 100-fold; this risk has been associated with
persistent HPV infection [78,79]. Similarly, chronic glucocorticoid therapy for the treatment of
autoimmune disease may predispose to both HPV infection and HPV related invasive anal cancer
[80,81]. (See "Major side effects of systemic glucocorticoids".)
Cigarette smoking Several case-control studies have noted a statistically significant risk of anal
cancer in smokers, especially current smokers [32,44,48,76,82-84]. In one series, compared with
controls without anal cancer, cigarette smoking was associated with a significantly increased risk of
anal cancer (RR 1.9 for 20 pack-years, RR 5.2 for 50 pack-years) [32]. Cigarette smoking is highly
associated with cervical neoplasia and is thought to act as a co-carcinogen [85]. (See "Cervical
cancer screening tests: Techniques for cervical cytology and human papillomavirus testing".)
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Here are the patient education articles that are relevant to this topic. We encourage you to print or
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subjects by searching on patient info and the keyword(s) of interest.)
Basics topic (see "Patient information: Anal cancer (The Basics)")
SUMMARY
Four distinct categories of tumors arise in the anal region: (see 'Anatomy and
histology' above)
Tumors that develop from any of the three types of mucosa lining the anal canal are
termed anal canal cancers. Tumors arising in the transitional or squamous mucosa are
squamous cell cancers (SCCs) and appear to behave similarly, despite their sometimes

variable morphologic appearance. By convention, most series that report outcomes of

anal cancer refer exclusively to these tumors.
Adenocarcinomas arising from glandular elements within the anal canal are rare, but
appear to share a similar natural history to rectal adenocarcinomas; they are treated
similarly. (See "Clinical features, staging, and treatment of anal cancer", section on
'Treatment of localized adenocarcinoma of the anal canal'.)
Primary rectal SCCs, which are very rare, can be difficult to distinguish from anal
cancers, and they should be treated according to the same approach as anal cancer.
(See "Clinical features, staging, and treatment of anal cancer", section on 'Rectal
squamous cell cancers'.)
Tumors arising within the hair-bearing skin at or distal to the squamous mucocutaneous
junction have been referred to as anal margin cancers. However, the preferred term is
perianal skin cancers. (See "Clinical features, staging, and treatment of anal cancer",
section on 'Staging' and "Clinical features, staging, and treatment of anal cancer",
section on 'Treatment of perianal skin cancers'.)
Historically, the medical community has distinguished between tumors arising in the perianal
hair-bearing skin and tumors in the anal canal in terms of treatment. The former are thought to
be biologically similar to squamous cell carcinomas (SCCs) of the skin rather than SCCs of the
aerodigestive tract, and have been staged and treated as skin rather than anal canal cancers.
However, it is not clear that there are any true differences in the natural history or response to
treatment for these two types of SCCs. Most clinicians treat SCC lesions of the perianal skin
as anal canal cancers using radiation therapy (RT) and concurrent chemotherapy. Local
treatment, surgery, or local RT (electrons) is used only when the lesion is very separate from
the anal verge and is a discrete skin lesion. (See 'Perianal skin cancers' above.)
The majority of tumors arising in the transitional or squamous mucosa of the anal canal are
SCCs. The term anal cancer by common definition refers to SCCs arising within the mucosa
of the anal canal. In contrast, adenocarcinomas arising from glandular elements within the
anal canal are rare but appear to share a similar natural history to rectal adenocarcinomas.
They are treated in a manner that is similar to rectal carcinoma rather than anal cancer.
(See 'Anal canal tumors' above.)
Although it remains an uncommon cancer, the incidence of anal cancer is increasing in the
United States and other countries. (See 'Epidemiology and risk factors'above.)
An increased incidence has been associated with female gender, infection with human
papillomavirus (HPV), lifetime number of sexual partners, genital warts, cigarette smoking,
receptive anal intercourse, infection with human immunodeficiency virus (HIV), and other
causes of chronic immunosuppression. Thus, from an etiologic standpoint, anal cancer is
more similar to genital malignancies than it is to gastrointestinal tract cancers. (See 'Risk
factors' above.)
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