Opinion Articles
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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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 12 | 8 | 20 |
| 2024 Octubre | 97 | 41 | 138 |
| 2024 Septiembre | 133 | 30 | 163 |
| 2024 Agosto | 139 | 59 | 198 |
| 2024 Julio | 106 | 41 | 147 |
| 2024 Junio | 115 | 27 | 142 |
| 2024 Mayo | 99 | 46 | 145 |
| 2024 Abril | 90 | 31 | 121 |
| 2024 Marzo | 94 | 28 | 122 |
| 2024 Febrero | 85 | 29 | 114 |
| 2024 Enero | 90 | 43 | 133 |
| 2023 Diciembre | 118 | 21 | 139 |
| 2023 Noviembre | 90 | 26 | 116 |
| 2023 Octubre | 78 | 21 | 99 |
| 2023 Septiembre | 70 | 47 | 117 |
| 2023 Agosto | 60 | 17 | 77 |
| 2023 Julio | 48 | 34 | 82 |
| 2023 Junio | 49 | 27 | 76 |
| 2023 Mayo | 71 | 28 | 99 |
| 2023 Abril | 34 | 21 | 55 |
| 2023 Marzo | 54 | 29 | 83 |
| 2023 Febrero | 50 | 18 | 68 |
| 2023 Enero | 42 | 27 | 69 |
| 2022 Diciembre | 83 | 45 | 128 |
| 2022 Noviembre | 37 | 35 | 72 |
| 2022 Octubre | 36 | 18 | 54 |
| 2022 Septiembre | 39 | 37 | 76 |
| 2022 Agosto | 25 | 32 | 57 |
| 2022 Julio | 29 | 24 | 53 |
| 2022 Junio | 28 | 22 | 50 |
| 2022 Mayo | 29 | 31 | 60 |
| 2022 Abril | 45 | 43 | 88 |
| 2022 Marzo | 62 | 56 | 118 |
| 2022 Febrero | 55 | 33 | 88 |
| 2022 Enero | 48 | 33 | 81 |
| 2021 Diciembre | 46 | 37 | 83 |
| 2021 Noviembre | 47 | 34 | 81 |
| 2021 Octubre | 112 | 44 | 156 |
| 2021 Septiembre | 34 | 40 | 74 |
| 2021 Agosto | 24 | 41 | 65 |
| 2021 Julio | 19 | 34 | 53 |
| 2021 Junio | 29 | 40 | 69 |
| 2021 Mayo | 39 | 51 | 90 |
| 2021 Abril | 43 | 40 | 83 |
| 2021 Marzo | 49 | 21 | 70 |
| 2021 Febrero | 60 | 27 | 87 |
| 2021 Enero | 28 | 23 | 51 |
| 2020 Diciembre | 19 | 14 | 33 |
| 2020 Noviembre | 28 | 16 | 44 |
| 2020 Octubre | 20 | 13 | 33 |
| 2020 Septiembre | 40 | 17 | 57 |
| 2020 Agosto | 28 | 18 | 46 |
| 2020 Julio | 35 | 15 | 50 |
| 2020 Junio | 40 | 28 | 68 |
| 2020 Mayo | 21 | 23 | 44 |
| 2020 Abril | 32 | 11 | 43 |
| 2020 Marzo | 31 | 19 | 50 |
| 2020 Febrero | 4 | 1 | 5 |
| 2020 Enero | 3 | 1 | 4 |
| 2019 Diciembre | 10 | 3 | 13 |
| 2019 Noviembre | 4 | 3 | 7 |
| 2019 Septiembre | 4 | 3 | 7 |
| 2019 Agosto | 4 | 0 | 4 |
| 2019 Julio | 4 | 3 | 7 |
| 2019 Junio | 4 | 0 | 4 |
| 2019 Mayo | 7 | 11 | 18 |
| 2019 Abril | 2 | 6 | 8 |
| 2019 Marzo | 4 | 5 | 9 |
| 2019 Febrero | 0 | 3 | 3 |
| 2019 Enero | 2 | 0 | 2 |
| 2018 Diciembre | 4 | 1 | 5 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 3 | 1 | 4 |
| 2018 Febrero | 83 | 1 | 84 |
| 2018 Enero | 46 | 7 | 53 |
| 2017 Diciembre | 51 | 6 | 57 |
| 2017 Noviembre | 25 | 4 | 29 |
| 2017 Octubre | 27 | 4 | 31 |
| 2017 Septiembre | 22 | 6 | 28 |
| 2017 Agosto | 27 | 7 | 34 |
| 2017 Julio | 24 | 3 | 27 |
| 2017 Junio | 41 | 11 | 52 |
| 2017 Mayo | 27 | 3 | 30 |
| 2017 Abril | 27 | 6 | 33 |
| 2017 Marzo | 24 | 17 | 41 |
| 2017 Febrero | 25 | 16 | 41 |
| 2017 Enero | 23 | 8 | 31 |
| 2016 Diciembre | 48 | 1 | 49 |
| 2016 Noviembre | 50 | 14 | 64 |
| 2016 Octubre | 59 | 20 | 79 |
| 2016 Septiembre | 52 | 10 | 62 |
| 2016 Agosto | 47 | 8 | 55 |
| 2016 Julio | 50 | 16 | 66 |
| 2016 Junio | 28 | 5 | 33 |
| 2016 Mayo | 22 | 18 | 40 |
| 2016 Abril | 9 | 14 | 23 |
| 2016 Marzo | 13 | 0 | 13 |
| 2016 Febrero | 6 | 5 | 11 |
| 2016 Enero | 18 | 7 | 25 |
| 2015 Diciembre | 20 | 7 | 27 |
| 2015 Noviembre | 23 | 8 | 31 |
| 2015 Octubre | 26 | 1 | 27 |
| 2015 Septiembre | 24 | 11 | 35 |
| 2015 Agosto | 36 | 7 | 43 |
| 2015 Julio | 237 | 19 | 256 |
| 2015 Junio | 211 | 16 | 227 |
| 2015 Mayo | 325 | 31 | 356 |
| 2015 Abril | 231 | 20 | 251 |
| 2015 Marzo | 246 | 21 | 267 |
| 2015 Febrero | 191 | 11 | 202 |
| 2015 Enero | 142 | 32 | 174 |
| 2014 Diciembre | 164 | 20 | 184 |
| 2014 Noviembre | 146 | 29 | 175 |
| 2014 Octubre | 179 | 32 | 211 |
| 2014 Septiembre | 131 | 30 | 161 |
| 2014 Agosto | 144 | 30 | 174 |
| 2014 Julio | 150 | 43 | 193 |
| 2014 Junio | 180 | 41 | 221 |
| 2014 Mayo | 171 | 34 | 205 |
| 2014 Abril | 118 | 20 | 138 |
| 2014 Marzo | 156 | 41 | 197 |
| 2014 Febrero | 111 | 34 | 145 |
| 2014 Enero | 133 | 36 | 169 |
| 2013 Diciembre | 116 | 31 | 147 |
| 2013 Noviembre | 38 | 20 | 58 |
| 2013 Octubre | 25 | 20 | 45 |
| 2013 Septiembre | 18 | 32 | 50 |
| 2013 Agosto | 29 | 52 | 81 |
| 2013 Julio | 14 | 35 | 49 |
| 2013 Junio | 18 | 59 | 77 |
| 2013 Mayo | 36 | 55 | 91 |
| 2013 Abril | 12 | 28 | 40 |
| 2013 Marzo | 40 | 22 | 62 |
| 2013 Febrero | 85 | 14 | 99 |
| 2013 Enero | 29 | 11 | 40 |
| 2012 Diciembre | 30 | 12 | 42 |
| 2012 Noviembre | 1 | 2 | 3 |
| 2012 Octubre | 2 | 6 | 8 |
| 2012 Agosto | 1 | 0 | 1 |
| 2012 Julio | 3 | 0 | 3 |
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