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Early Detection of Anal Intraepithelial Neoplasia in High-Risk Patients
Detección precoz de la neoplasia intraepitelial anal en pacientes de alto riesgo
C. Ferrándiz-Pulido
Servicio de Dermatología, Hospital Universitario Vall d’Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain
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B, Grade 2 AIN showing a papillomatous pattern with vascular punctation. C, Acetowhite plaque with abnormal vascularization in the upper right and left quadrants in a patient diagnosed with grade 2 AIN. D, Extensive acetowhite plaque with a cobblestone appearance in lower right and left quadrants in a patient with grade 2 AIN. E, Circumscribed acetowhite plaque in the upper left quadrant, corresponding to grade 2 AIN. F, Circumferential acetowhite plaques in a patient with grade 3 AIN. G, Acetowhite plaques and friable mucosa with hemorrhagic, erosive areas in a patient with grade 3 AIN. H, Acetowhite plaque and thick, tortuous vessels in upper quadrants. I, Exudative, hemorrhagic mass in a patient with infiltrating squamous cell carcinoma.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "E. Sendagorta, P. Herranz, H. Guadalajara, F.X. Zamora" "autores" => array:4 [ 0 => array:2 [ "nombre" => "E." "apellidos" => "Sendagorta" ] 1 => array:2 [ "nombre" => "P." 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Ferrándiz-Pulido" "autores" => array:1 [ 0 => array:3 [ "nombre" => "C." "apellidos" => "Ferrándiz-Pulido" "email" => array:1 [ 0 => "40879cfp@comb.cat" ] ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Dermatología, Hospital Universitario Vall d’Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Detección precoz de la neoplasia intraepitelial anal en pacientes de alto riesgo" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Screening tests are applied systematically to an asymptomatic population in order to detect abnormalities, establish an early diagnosis, provide early treatment, and avoid the consequences of delayed diagnosis.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Screening programs are particularly effective in the detection of common cancers for which good, cost-effective tests are available, affordable, acceptable, and accessible to the majority of the at-risk population. Examples are cervical cancer and breast cancer in women. This issue of <span class="elsevierStyleItalic">Actas Dermo-Sifiliográficas</span> includes an article that reviews the need for early detection of anal intraepithelial neoplasia (AIN) in high-risk patients, a topic that has received much attention in the literature in recent years, mainly because of the steadily rising incidence of this disease.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Until the early 1990s anal cancer was not considered a major public health concern because the frequency was low and patients were usually of advanced age; AIN was more common in women and accounted for 5% of cases of gastrointestinal neoplasia.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The incidence began to rise in Europe and North America in the 1990s, however, and interestingly, the prevalence was higher in young men. It soon became clear that most of the patients were homosexuals infected with human immunodeficiency virus (HIV), among whom the incidence was much higher than expected. At present, despite the introduction of highly active antiretroviral therapy, anal cancer is the most common non–AIDS-defining neoplasia in HIV-infected patients and the incidence has increased most in this population.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">To understand the pathophysiology of anal cancer and its similarity to cervical cancer, it is essential to understand the anatomy of the area. The anatomical anal canal extends from the dentate line to the anal verge. The dentate line, at the point where the squamous epithelium and the columnar epithelium of the rectum meet, is the most important macroscopic reference point of the anal mucosa because tumors located above or below it have distinct drainage patterns. Above this line, tumors drain to the perirectal and paravertebral lymph nodes and below it they drain to the femoral and inguinal lymph nodes. The perianal space surrounds the anal canal to a distance of 5<span class="elsevierStyleHsp" style=""></span>cm. Because anal tumors originate in the squamous epithelium of the perianal space or of the anal canal, over 80% of these cancers are of the squamous cell type.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Like cancer of the cervix, penis or vulva, squamous epithelial dysplasia of the anal canal (known as AIN) is considered a carcinoma in situ. Also like cancer of the cervix, penis or vulva, AIN is classified into 3 grades of dysplasia, defined by the degree of the cytologic atypia and the degree of epithelial involvement. AIN grade 1 refers to a low-grade squamous lesion, whereas grades 2 and 3 are high-grade squamous cell or in situ carcinomas.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> These tumors typically occur in the squamous epithelium below the dentate line and their diagnosis always requires a biopsy for pathology.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The pathogenesis and clinical course of anal cancer are also very similar to those of cervical cancer. Both mucosas have a transition zone between the columnar and squamous epithelia. In both cases intraepithelial neoplasia always precedes the appearance of an invasive carcinoma and the transition period may be very long. Furthermore, as occurs in cervical cancer, over 90% of anal cancers are associated with human papillomavirus (HPV) infection, a major oncogenic stimulus; HPV-16 and HPV-18 are the most common genotypes.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> However, we know that AIN progresses much more slowly and less frequently towards invasive anal cancer than cervical intraepithelial neoplasia progresses, suggesting that there are relevant factors in addition to HPV.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The rising incidence of anal cancer has made it necessary to establish early detection programs. Because systematic screening for cervical cancer reduces the risk of invasive cervical cancer, early diagnosis and treatment of AIN should also reduce anal cancer. However, before establishing a program for early diagnosis of anal cancer, we must first determine the target population for screening, the optimal screening intervals, the long-term recurrence rates, and whether we have effective treatments that improve the prognosis. Our current lack of knowledge of the pathogenesis and natural history of anal cancer makes it difficult to answer these questions.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In general, AIN screening programs reveal higher incidences than cervical cancer screening programs do. In principle, AIN screening programs should be applied to groups at risk for this disease. The results of screening programs have shown that groups at high risk include not only HIV-infected men who have sex with men (MSM) but also non-MSM patients who are HIV-infected and MSM who are not HIV-infected; thus, the target population for screening has broadened.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The range of at-risk patients has now been extended to chemically immunosuppressed patients, such as recipients of solid-organ transplants, women infected with HIV, and women not infected with HIV who have a history of genital cancer. In a study in which women with HPV infection in the genital area underwent screening of the anal canal, 12% of biopsies revealed AIN.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The common denominator of these groups is the practice of anoreceptive sex or the extension of the HPV infection from the genital zone to the anal canal because of immunosuppression or a high viral load. However, HIV-infected MSM are very clearly the group with the highest incidence of AIN and should therefore be the main targets for AIN screening programs.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The main objective of AIN screening is to detect anal dysplasia early and to eradicate it, thus preventing progression to invasive lesions such as squamous cell carcinoma. Fortunately, more and better techniques for diagnosing and treating anal dysplasia and anal cancer are emerging and will undoubtedly reduce the morbidity and mortality of this disease. Anal cytology has been proposed as a method for AIN screening in high-risk patients.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The test must be done by an expert, so as to ensure that a sufficient number of cells representing the whole anal canal are obtained and to avoid, as far as possible, contaminants such as fecal remains. It is not necessary to prepare the colon, but the rectal vault must be emptied before the sample is obtained. As explained in an article in this issue of <span class="elsevierStyleItalic">Actas Demo-Sifiliográficas</span>, the cytology brush must be inserted into the anus, advanced 2<span class="elsevierStyleHsp" style=""></span>to 3<span class="elsevierStyleHsp" style=""></span>cm, and then removed with a rotary motion to obtain cells representing the whole anal canal; the sample must be fixed immediately. Several studies have shown good cost-effectiveness in HIV-infected patients screened every year and in HIV-uninfected MSM screened every 2 or 3 years, but there is no clear consensus in international guidelines on whether systematic anal cytology for AIN screening should be recommended in HIV-infected MSM.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> This technique is imperfect, however, because it gives false positives and false negatives. Therefore, molecular techniques for improving the sensitivity and specificity of AIN screening are being tested. Another problem of cytology is that it does not always indicate lesion severity, so in patients with an abnormal cytology, high-resolution anoscopy-guided biopsy should be used to identify dysplastic lesions.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Though anoscopy is similar to colposcopy, specific training is required to become an expert in the technique. At present, the lack of experts in anoscopy limits the creation of new screening programs. In our hospital an anal dysplasia screening department has been functioning for just over a year and in one year it dealt with 200 MSM and HIV-infected patients. During this period we detected 58 patients with condylomata and 11 patients with AIN 2 and 3, who were treated successfully.</p><p id="par0045" class="elsevierStylePara elsevierViewall">What we do have today is excellent primary prevention of HPV infection. All young girls in Spain are currently being vaccinated before their first sexual relations and the US Food and Drug Administration has also approved the use of the tetravalent vaccine in males aged 9 to 26 years in order to reduce the incidence of condyloma acuminata associated with the genotypes covered.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> However, it is not clear what subgroup should be vaccinated because it is best to vaccinate before sexual relations begin and vaccination has not been proven to reduce the incidence of anal cancer.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In some population groups anal carcinoma is a common tumor and it has a premalignant period that can be detected by simple cytology. The cytologic diagnosis has reasonable sensitivity and high specificity, and histologic confirmation by high-resolution anoscopy is easily obtained if trained staff are available. The therapeutic arsenal for treating intraepithelial lesions is large, encompassing topical treatments such as imiquimod and 5-fluorouracil in addition to infrared coagulator, carbon dioxide laser therapy, and surgery. However, no optimal treatment for AIN has been established: the approach should be tailored according to the characteristics of the lesion, the patient, the availability of a treatment center, and its experience with AIN. Having a large therapeutic arsenal usually means that none of the treatments is optimally effective with minimal adverse effects. In my opinion, screening for anal cancer should be managed as screening for cervical cancer is: it should target selected populations, such as HIV-infected MSM. However, many studies are still needed to answer a series of questions. Can AIN screening reduce the incidence and mortality of anal cancer? What patient groups should screening target and how often should tests be done? Should high-resolution anoscopy be performed in all patients with a diagnosis of carcinoma of the cervix, vulva, or vagina? What about transplant patients with genital lesions caused by HPV infection? And what about MSM not infected with HIV? Whatever the answers may be, I think that dermatologists should join multidisciplinary teams specializing in the management and early diagnosis of these patients, so that we can contribute our opinion as experts in skin cancer and venereology.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Ferrándiz-Pulido C. Detección precoz de la neoplasia intraepithelial anal en pacientes de alto riesgo. Actas Dermosifiliogr. 2011;102:754-756.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cancer, nota descriptiva n° 297" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Organización Mundial de la Salud" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2011" "editorial" => "OMS" "editorialLocalizacion" => "Geneve" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L.G. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 8 | 19 |
| 2024 October | 97 | 41 | 138 |
| 2024 September | 133 | 30 | 163 |
| 2024 August | 139 | 59 | 198 |
| 2024 July | 106 | 41 | 147 |
| 2024 June | 115 | 27 | 142 |
| 2024 May | 99 | 46 | 145 |
| 2024 April | 90 | 31 | 121 |
| 2024 March | 94 | 28 | 122 |
| 2024 February | 85 | 29 | 114 |
| 2024 January | 90 | 43 | 133 |
| 2023 December | 118 | 21 | 139 |
| 2023 November | 90 | 26 | 116 |
| 2023 October | 78 | 21 | 99 |
| 2023 September | 70 | 47 | 117 |
| 2023 August | 60 | 17 | 77 |
| 2023 July | 48 | 34 | 82 |
| 2023 June | 49 | 27 | 76 |
| 2023 May | 71 | 28 | 99 |
| 2023 April | 34 | 21 | 55 |
| 2023 March | 54 | 29 | 83 |
| 2023 February | 50 | 18 | 68 |
| 2023 January | 42 | 27 | 69 |
| 2022 December | 83 | 45 | 128 |
| 2022 November | 37 | 35 | 72 |
| 2022 October | 36 | 18 | 54 |
| 2022 September | 39 | 37 | 76 |
| 2022 August | 25 | 32 | 57 |
| 2022 July | 29 | 24 | 53 |
| 2022 June | 28 | 22 | 50 |
| 2022 May | 29 | 31 | 60 |
| 2022 April | 45 | 43 | 88 |
| 2022 March | 62 | 56 | 118 |
| 2022 February | 55 | 33 | 88 |
| 2022 January | 48 | 33 | 81 |
| 2021 December | 46 | 37 | 83 |
| 2021 November | 47 | 34 | 81 |
| 2021 October | 112 | 44 | 156 |
| 2021 September | 34 | 40 | 74 |
| 2021 August | 24 | 41 | 65 |
| 2021 July | 19 | 34 | 53 |
| 2021 June | 29 | 40 | 69 |
| 2021 May | 39 | 51 | 90 |
| 2021 April | 43 | 40 | 83 |
| 2021 March | 49 | 21 | 70 |
| 2021 February | 60 | 27 | 87 |
| 2021 January | 28 | 23 | 51 |
| 2020 December | 19 | 14 | 33 |
| 2020 November | 28 | 16 | 44 |
| 2020 October | 20 | 13 | 33 |
| 2020 September | 40 | 17 | 57 |
| 2020 August | 28 | 18 | 46 |
| 2020 July | 35 | 15 | 50 |
| 2020 June | 40 | 28 | 68 |
| 2020 May | 21 | 23 | 44 |
| 2020 April | 32 | 11 | 43 |
| 2020 March | 31 | 19 | 50 |
| 2020 February | 4 | 1 | 5 |
| 2020 January | 3 | 1 | 4 |
| 2019 December | 10 | 3 | 13 |
| 2019 November | 4 | 3 | 7 |
| 2019 September | 4 | 3 | 7 |
| 2019 August | 4 | 0 | 4 |
| 2019 July | 4 | 3 | 7 |
| 2019 June | 4 | 0 | 4 |
| 2019 May | 7 | 11 | 18 |
| 2019 April | 2 | 6 | 8 |
| 2019 March | 4 | 5 | 9 |
| 2019 February | 0 | 3 | 3 |
| 2019 January | 2 | 0 | 2 |
| 2018 December | 4 | 1 | 5 |
| 2018 November | 2 | 0 | 2 |
| 2018 October | 3 | 1 | 4 |
| 2018 February | 83 | 1 | 84 |
| 2018 January | 46 | 7 | 53 |
| 2017 December | 51 | 6 | 57 |
| 2017 November | 25 | 4 | 29 |
| 2017 October | 27 | 4 | 31 |
| 2017 September | 22 | 6 | 28 |
| 2017 August | 27 | 7 | 34 |
| 2017 July | 24 | 3 | 27 |
| 2017 June | 41 | 11 | 52 |
| 2017 May | 27 | 3 | 30 |
| 2017 April | 27 | 6 | 33 |
| 2017 March | 24 | 17 | 41 |
| 2017 February | 25 | 16 | 41 |
| 2017 January | 23 | 8 | 31 |
| 2016 December | 48 | 1 | 49 |
| 2016 November | 50 | 14 | 64 |
| 2016 October | 59 | 20 | 79 |
| 2016 September | 52 | 10 | 62 |
| 2016 August | 47 | 8 | 55 |
| 2016 July | 50 | 16 | 66 |
| 2016 June | 28 | 5 | 33 |
| 2016 May | 22 | 18 | 40 |
| 2016 April | 9 | 14 | 23 |
| 2016 March | 13 | 0 | 13 |
| 2016 February | 6 | 5 | 11 |
| 2016 January | 18 | 7 | 25 |
| 2015 December | 20 | 7 | 27 |
| 2015 November | 23 | 8 | 31 |
| 2015 October | 26 | 1 | 27 |
| 2015 September | 24 | 11 | 35 |
| 2015 August | 36 | 7 | 43 |
| 2015 July | 237 | 19 | 256 |
| 2015 June | 211 | 16 | 227 |
| 2015 May | 325 | 31 | 356 |
| 2015 April | 231 | 20 | 251 |
| 2015 March | 246 | 21 | 267 |
| 2015 February | 191 | 11 | 202 |
| 2015 January | 142 | 32 | 174 |
| 2014 December | 164 | 20 | 184 |
| 2014 November | 146 | 29 | 175 |
| 2014 October | 179 | 32 | 211 |
| 2014 September | 131 | 30 | 161 |
| 2014 August | 144 | 30 | 174 |
| 2014 July | 150 | 43 | 193 |
| 2014 June | 180 | 41 | 221 |
| 2014 May | 171 | 34 | 205 |
| 2014 April | 118 | 20 | 138 |
| 2014 March | 156 | 41 | 197 |
| 2014 February | 111 | 34 | 145 |
| 2014 January | 133 | 36 | 169 |
| 2013 December | 116 | 31 | 147 |
| 2013 November | 38 | 20 | 58 |
| 2013 October | 25 | 20 | 45 |
| 2013 September | 18 | 32 | 50 |
| 2013 August | 29 | 52 | 81 |
| 2013 July | 14 | 35 | 49 |
| 2013 June | 18 | 59 | 77 |
| 2013 May | 36 | 55 | 91 |
| 2013 April | 12 | 28 | 40 |
| 2013 March | 40 | 22 | 62 |
| 2013 February | 85 | 14 | 99 |
| 2013 January | 29 | 11 | 40 |
| 2012 December | 30 | 12 | 42 |
| 2012 November | 1 | 2 | 3 |
| 2012 October | 2 | 6 | 8 |
| 2012 August | 1 | 0 | 1 |
| 2012 July | 3 | 0 | 3 |
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