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© Borgis - Nowa Medycyna 2/2022, s. 49-57 | DOI: 10.25121/NM.2022.29.2.49
Daria Marcinkowska1, *Sławomir Glinkowski1, Michał Spych2
Anal cancer – a multidisciplinary medical challenge. Diagnosis and treatment
Rak odbytu – multidyscyplinarny problem medyczny. Diagnostyka i leczenie
1Department of General and Oncological Surgery, Tomaszów Health Centre
2Nu-Med Specialist Oncology Hospital, Tomaszów Mazowiecki
Streszczenie
Rak odbytu jest nowotworem dość rzadko występującym, jednak obserwowany jest wzrost częstości zachorowań. Wielu autorów uważa, że zwiększona częstość zachorowań związana jest ze wzrostem ilości infekcji wirusem HPV oraz HIV. Występowanie raka odbytu szczególnie związane jest z podtypami 16, 18, 31, 33, 45 wirusa HPV. Podtypy 16 i 18 uważane są za najbardziej onkogenne i wpływają na rozwój wielu innych nowotworów, w tym przede wszystkim raka szyjki macicy. W Polsce szczepienie przeciwko HPV wciąż jest nierefundowane. Symptomatyka raka odbytu często powoduje wydłużenie czasu do wprowadzenia właściwego leczenia. Objawy mogą sugerować inne choroby proktologiczne, w tym krwawienie z kolumn hemoroidalnych. Leczeniem z wyboru jest jednoczasowa chemioradioterapia. Leczenie chirurgiczne stanowi element „leczenia ratunkowego” w przypadkach nawrotów, może stanowić przygotowanie do chemioradioterapii. Jednak najważniejszym zadaniem chirurgii w leczeniu raka odbytu jest właściwa diagnostyka – rozpoznanie choroby oraz pobranie wycinków do badania histopatologicznego celem potwierdzenia diagnozy. Schemat leczenia pozostaje niezmienny od lat, a największe możliwości jego zmiany są związane z nadziejami na wprowadzenie leczenia immunologicznego przypadków nowotworów związanych z wirusem HPV, czyli według piśmiennictwa aż 85% przypadków.
Summary
Although anal cancer is relatively rare, an increase in its incidence has been observed. Many authors attribute this increase to higher rates of human papilloma virus (HPV) and human immunodeficiency virus (HIV) infections. The incidence of anal cancer is particularly associated with HPV subtypes 16, 18, 31, 33, 45. Subtypes 16 and 18 are considered to be the most oncogenic and contribute to the development of many other malignancies, cervical cancer in particular. In Poland, HPV vaccination is still not reimbursed. Symptomatology of anal cancer often delays appropriate treatment. Symptoms may suggest other proctological conditions, including haemorrhoidal bleeding. Concurrent chemoradiotherapy is the treatment of choice. Surgical treatment is used as part of ”salvage treatment” in cases of recurrence, and may be a step to prepare the patient for chemoradiotherapy. However, correct diagnosis of the disease and collection of histopathological biopsies to confirm the diagnosis, is the most important role of surgery in the treatment of anal cancer. The treatment regimen has remained unchanged for years, and the greatest potential for change is in the hopes of introducing immunological treatment for cancers related to HPV, which, according to the literature, accounts for up to 85% of cases.



Introduction
Anal cancer is a rare neoplasm, but there has been a gradual increase in its incidence in recent years. According to the ICD-10 classification, this neoplasm is classified as C21 – malignant neoplasm of anus and anal canal. We present data on anal canal and anal verge cancer, including epidemiology, symptoms, diagnosis and treatment regimen.
Epidemiology
In recent years, there has been a gradual increase in the incidence of anal canal cancer. One hypothesis explaining this phenomenon is the increased incidence of HPV and HIV infections as a result of risky sexual behaviours. Risk factors include homosexual intercourse and an increased number of sexual partners. HIV has a significant negative impact on the body’s immune mechanisms, allowing cancer to develop. According to various sources, anal cancer accounts for ≤ 1% to ≤ 3% of colorectal cancers, with some sources reporting even 5% (1, 2). On average, it is assumed to account for approximately 2% of all colorectal cancers.
According to the National Cancer Registry, 200 cases of this type of cancer were registered in 2011. Increased incidence was recorded in women, i.e. 141 vs. 59 in men. At the same time, 269 deaths from this cancer were registered and here the proportions were reversed, i.e. 143 men vs. 126 women (3). The mean age of onset for this malignancy was estimated at 60-65 years of age. Standardised incidence and mortality rates by sex are shown in table 1.
Tab. 1. Standardised incidence and mortality rates
 Standardised incidence rate [thousand/year]Standardised mortality rate [thousand/year]
Women0.4/1000.3/100
Men0.2/100 0.5/100
Unfortunately, these are the most recent data on anal cancer available on the National Cancer Registry website. More recent information can be found on Onkonet, which reports that 100 and 186 cases of anal cancer were registered among men and women in 2017, respectively (4).
Squamous cell carcinoma (carcinoma planoepitheliale) is the most commonly diagnosed type of cancer (63%). Adenocarcinoma can also occur in the anal canal, but it accounts for approximately 3-10% of cancers in this location. This is due to the anatomy of this area, as anal cancer most often occurs in the transition zone between the squamous epithelium of the anal canal and the glandular epithelium of the rectum. Transitional cell carcinomas that cannot be clearly classified into any of the previous groups account for nearly 20%. If histopathology is indicative of squamous cell carcinoma, then anal cancer is diagnosed. Squamous cell carcinoma of the rectum occurs sporadically and can be only diagnosed if the tumour mass is not connected to the anal canal. Other neoplasms found in the anal canal are extremely rare and include melanoma, basal cell carcinoma, Bowen’s disease and Paget’s disease.
Symptoms
Anal bleeding is the most common first symptom of anal cancer. This non-specific manifestation is unfortunately overinterpreted as a symptom of haemorrhoidal disease. It occurs in approximately 45% of patients with anal cancer (2). It is sometimes underestimated by patients who initially try to self-medicate with over-the-counter drugs. Also, many doctors prescribe treatment recommended for haemorrhoidal disease for patients presenting with anal bleeding without first examining them. In any case of anal bleeding, a thorough history and physical examination, including a rectal examination, is fundamental. Patients should also undergo ano- or rectoscopy to exclude other possible causes of bleeding.
Ulceration, usually diagnosed earlier as it raises patient’s concerns, is another lesion that may raise the suspicion of anal cancer. At a later stage, the patient may experience pain or report a visible or palpable lump. In addition, symptoms such as pruritus, discomfort in the anal area and burning sensation may be present. These are also non-specific and may occur in various anal conditions.
On rectal examination, a thickening, tumour/bump, ulceration or lesion resembling chronic anal canal fissure with thickened, raised edges may be palpable. A tumour of the anal verge may be visible only as an irregular mucosal thickening, sometimes also with surrounding inflammatory reaction. The lesion may also be macroscopically invisible and unpalpable on rectal examination.
The presence of a tumour is found at various stages of the disease, sometimes already at a significantly advanced stage. Lymphadenopathy, especially involving the inguinal lymph nodes, which are easily accessible on examination, may be another alarming symptom. This is due to the anatomical structure of this area and the flow of lymph, which drains from the anal canal area to the inguinal nodes, the perirectal nodes, the external iliac nodes, the internal iliac nodes and the common iliac nodes.
Symptoms of gastrointestinal obstruction, fistulas, and generalised abdominal and pelvic pain are signs of significant disease progression.
Risk factors
Research has identified risk factors that have been proven to have a direct impact on the development of anal canal cancer. HPV infection is the most important risk factor for anal canal cancer. Subtypes 16 and 18 pose the greatest risk, but subtypes 31, 33 and 45 are also risk factors (5). HPV infection is found in 80-85% of anal canal cancer cases (2), with subtypes 16 and 18 being the most common. Anal canal cancer may be preceded by condylomas. Other significant risk factors for anal canal cancer are:
– HIV,
– passive anal intercourse, especially among HIV-positive homosexual men,
– having multiple sexual partners,
– a history of cervical, vaginal or vulvar cancer,
– smoking (especially in women),
– immunosuppressive treatment, autoimmune diseases,
– a history of papillary lesions of the anal or genital area,
– a history of other cancers with HPV aetiology.
A history of proctological diseases, especially chronic ones such as anal fistula, chronic anal fissure, recurrent anal abscesses, is also likely to play a role.
According to the guidelines, coexisting anal fistula at the time of diagnosis of anal cancer occurs in up to 25% of patients (3).
Gender and race are also important in determining the risk of anal canal cancer. This type of malignancy is more common in women and among African-Americans (5).
Conducted research has also found that anal intraepithelial neoplasia (AIN) is likely to be a precursor for anal canal cancer, as is cervical intraepithelial neoplasia (CIN) for cervical cancer.
Diagnosis
The following investigations should be performed in the following order if a patient reports symptoms that arouse oncological vigilance:
1. Collecting a thorough history is always fundamental. It is necessary to determine the duration of symptoms, the coexistence of other diseases, permanent treatments, and family history of cancer.
2. Physical examination, including rectal exam, is another element of the first stage of diagnosis. In women, vaginal examination is also necessary.
3. Ano- or rectoscopy should then be performed in a patient reporting alarming symptoms. This will allow other possible causes of symptoms to be ruled out. During the examination, biopsy specimens should be taken for histopathological examination. In the case of women, a gynaecological examination and cytology are also necessary to exclude metastases or other cancerous foci.
4. The progression of the neoplastic process is assessed using available imaging tools, usually transrectal ultrasound or contrast-enhanced abdominal/pelvic CT scan. Pelvic MRI may also be performed in doubtful cases or for an unambiguous assessment.

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Piśmiennictwo
1. Sudoł-Szopińska I, Szczepkowski M, Jakubowski W: Anal ultrasound in the diagnosis of anal carcinoma. Radiol Oncol 2001; 35(4): 273-276.
2. Rao S, Gurren MG, Khan K et al.: Anal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Onco 2021; 32(9): 1087-1100.
3. Ewerolimus we wskazaniach: nowotwór złośliwy jelita krętego (c17.2), nowotwór złośliwy odbytnicy (C20), nowotwór złośliwy odbytu, umiejscowienie nieokreślone (C21.0). Program leczenia w ramach świadczenia chemioterapii niestandardowej. Raport w sprawie oceny świadczenia opieki zdrowotnej. Raport Nr: AOTM-OT-431-11/2014. https://bipold.aotm.gov.pl/assets/files/zlecenia_mz/2014/078/RPT/078_OT_431_11_Ewerolimus_C17%202_C20_C210.pdf.
4. https://www.onkonet.pl/dl_npp_rakodbytu.php.
5. http://onkologia.org.pl/odbyt-kanal-odbytu/.
6. Nawrocki G: Współczesne metody leczenia raka odbytu. Post Nauk Med 2013; 8: 572-576.
7. Benson AB, Venook AP, Al-Hawary MM et al.: Anal Carinoma. Clinical Practice Guidelines in Oncology. JNCCN 2018; 16(7): 852-871.
8. http://www.onkonet.pl/dp npp rakodbytu.html (dostęp: 29.01.2021).
9. https://szczepienia.pzh.gov.pl/szczepionki/hpv/.
10. Geh I, Gollins S, Renehan A et al.: Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) – Anal Cancer. Colorectal Dis 2017; 19(1): 82-97.
otrzymano: 2022-03-14
zaakceptowano do druku: 2022-04-04

Adres do korespondencji:
*Sławomir Glinkowski
Oddział Chirurgii Ogólnej i Onkologicznej Tomaszowskie Centrum Zdrowia
ul. Jana Pawła II 35, 97-200 Tomaszów Mazowiecki
tel.: +48 608-177-914
drsg@wp.pl

Nowa Medycyna 2/2022
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