Giant Perianal Tumour Arising from Condyloma Acuminatum in a Patient Living with HIV-1

Giant Perianal Tumour Arising from Condyloma Acuminatum in a Patient Living with HIV-1 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Giant Perianal Tumour Arising from Condyloma Acuminatum in a Patient Living with HIV-1 Xiang Liu, Xueling Zhu, Zhikai Wan, Guanjing Lang, Ying Huang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1916215/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Background Perianal cancer is a relatively rare disease, but it is prevalent in men who have sex with men and in patients who are positive for human immunodeficiency virus (HIV). Here, we report a case of a massive anal squamous cell carcinoma that measured 19 cm in length and 10 cm in diameter in a male patient living with HIV. Case presentation A 28-year-old man with a 5-year history of peri-anal condyloma acuminatum developed a rapidly enlarging mass in the anal region since the past few months. He had both HIV and syphilis infection, but never sought further treatment. Pathological analysis and immunohistochemistry confirmed squamous cell carcinoma with high-risk HPV infection. After multi-disciplinary treatment, albumin-paclitaxel combined with anti-programmed cell death protein 1 therapy and simultaneous antiretroviral therapy was initiated. The mass began to shrink after chemotherapy, but this did not prevent tumor progression. He eventually died from tumor-cachexia. Conclusion Early screening and treatment of perianal disease can help prevent progression to invasive anal carcinoma in high-risk groups such as men who have sex with men and immunosuppressed patients. perianal cancers squamous cell carcinoma Human immunodeficiency virus Giant Figures Figure 1 Figure 2 Figure 3 Background Malignant perianal lesions account for only < 3% of all gastrointestinal tumors and are therefore considered quite rare[ 1 ]. Its most common histologic variant is squamous cell carcinoma (SCC). The most important causative factor for anal SCC (aSCC) is human papillomavirus (HPV) infection. Other high-risk factors include human immunodeficiency virus (HIV) infection and men who have sex with men (MSM)[ 2 , 3 ]. The incidence of anal cancer is higher in HIV-infected than non-HIV-infected patients[ 4 ]. Studies have demonstrated that the larger the tumor, the worse the prognosis of aSCC[ 5 ]. Tumors > 5 cm in size were classified as T3. To our knowledge, no relevant literature has reported aSCC with a tumor size > 15 cm. Here, we report a case of a giant 19-cm-long aSCC in a male patient who had both HIV and syphilis infection but never received any anti-infective treatment. Case Presentation A 28-year-old homosexual man sought medical attention for a 5-year history of peri-anal condyloma acuminatum that had been rapidly increasing in size for the last several months. He had a 3-year history of HIV infection and syphilis but did not receive combination antiretroviral therapy (cART) and the treatment for syphilis. The patient appeared emaciated and had low-grade fever with fatigue at the time of presentation. Physical examination revealed a large, irregular, cauliflower-like, ulcerated mass (19 cm × 10 cm) and foul-smelling exudate; the mass covered almost the entire perineum (Fig. 1 A). Given the exceptionally large size of the tumor and the associated bleeding risk, the patient was unable to maintain a sitting or supine position. Moreover, rectal examination and proctoscopy could not be carried out. Laboratory examination revealed CD4 + T-cell count was 84 cells/mm 3 , and hemoglobin was 61 g/L. The patient also showed hypoalbuminemia (20 g/L) and hypocholesterolemia (1.92 mmol/L); however, there was no evidence that he was involved in opportunistic infections. Positron-emission tomography–computed tomography showed that the lesion had invaded and destroyed the surrounding structures of the anorectum and pelvis, and multiple enlarged lymph nodes were found in the groin region (Fig. 2 ). Pathological analysis and immunohistochemistry indicated SCC with diffuse P16 and Ki-67 expression, and P53 (10%), P40 (+), and P63 (+) (Fig. 3 ). HPV 31-DNA was detected in the tumor tissue. Chemotherapy combined with radiation therapy was identified as the final treatment scheme after multi-disciplinary treatment (MDT). Albumin-paclitaxel combined with anti-programmed cell death protein 1 (PD-1) therapy and simultaneous antiretroviral therapy was initiated. The lesion began to shrink after the first cycle of chemotherapy (Fig. 1 B). After the fifth cycle, local necrosis and hemorrhage of lesions were relieved, and the tumor size finally decreased to 9 cm (length) by 5 cm (base diameter) (Fig. 1 C). The tumor was temporally controlled by our therapy. Unfortunately, the growth of cancer cells have lost control once again 10 months after diagnosis, and he eventually died from tumor-cachexia at the time of writing this report. Despite the ultimate outcome of this patient would be expected, we believed our treatment successfully extended his lifespan. Discussion And Conclusion We report a case of SSC from perianal condyloma in a patient who had both HIV and syphilis infection but had never received any anti-infective treatment. We believe that this is the largest perianal mass reported to date. As the tumor was extensively invasive at the time of the patient’s presentation, it could not be surgically resected and could only be palliatively treated with chemotherapy combined with radiotherapy. With our treatment, the patient’s condition gradually improved, as evidenced by a significant reduction in tumor size, significant relief from hypothermia and fatigue, gradual progress in clinical indicators, and significant enhancement in the quality of life. However, it can be presumed that the patient's overall prognosis is poor. Such a large tumor is reminiscent of Buschke–Löwenstein tumor or giant condyloma acuminatum, which presents as a large verrucous tumor in the genital area with expansive and destructive growth[ 6 ]. Only 40–45% of reported cases are diagnosed as simple condyloma acuminatum without invasion, whereas 50–55% cases show malignant transformation to SCC (verrucous carcinoma variant)[ 7 ]. It is possible that there is a pathological transformation of the condyloma acuminatum to a malignant invasive squamous carcinoma in the presence of high-risk HPV and other risk factors [ 8 ]. A local pathological biopsy suggested SCC and high-risk HPV infection (P16+) in our patient with history of condyloma acuminatum, which appears to reveal this pathological transformation. Anal SCC accounts for 90% of all anal tumors, and the incidence of anal margin SCC is 4–5 times lower than that of anal canal SCC[ 8 , 9 ]. The incidence of anal cancer is increasing in certain specific populations such as HIV-infected patients, MSM, women with genital tumors, and patients with condyloma acuminatum or inflammatory bowel disease[ 10 ]. A long-term follow-up study in France confirmed that the risk of anal cancer was highest in HIV-positive and MSM populations, but the risk of anal cancer decreased in the cART era, suggesting the importance of cART in reducing the incidence of non-AIDS-defining tumors[ 11 ]. HPV infection is the most important risk factor for the development of aSCC. Numerous serotypes of HPV are known, with serotypes 16, 18, 31, 33, and 35 being the most associated with tumors, and serotypes 6 and 11 being the most associated with condyloma acuminata[ 12 ]. Our patient had many risk factors for cancer, such as MSM, untreated HIV infection, untreated condyloma acuminata, and HPV 31 positivity. According to the NCCN Clinical Practice Guidelines in Oncology, version 1.2022, the main treatment for aSCC is chemoradiotherapy (CRT), and the first-line treatment is 5-fluorouracil (5-FU) and mitomycin C (MMC)combined with radiotherapy[ 13 ]. When multiple metastases are present in the tumor, platinum combined with paclitaxel is recommended for chemotherapy and, if necessary, anti-PD-1/programmed death ligand 1 (PD-L1) immunotherapy[ 1 ]. HIV-positive aSCC patients with adequate immune reconstitution and virologic suppression can receive a standard CRT regimen, but patients who have uncontrolled HIV-related complications before the diagnosis of aSCC should receive a reduced dose of CRT[ 13 , 14 ]. Studies suggest that survival in HIV-positive aSCC patients in the cART era is similar to that of HIV-negative aSCC patients, but there is no evidence to suggest that cART improves survival in HIV-positive aSCC patients[ 15 ]. In addition, stage T1N0M0 aSCC < 2 cm in size without lymph node metastases and distant metastases can be surgically resected[ 13 ]. Compared to aSCC, there are no guidelines for the optimal treatment of rectal squamous cell carcinoma( rSCC). Many reports currently support the use of the same CRT approach for rSCC as for aSCC[ 16 ]. In this case, the patient's perianal mass was extremely large and had invaded the rectal and surrounding tissues. After MDT discussion, the patient was treated with albumin paclitaxel combined with anti-PD-1 immunotherapy, and the perianal mass shrank significantly and the clinical indices gradually improved, suggesting that the treatment was effective. The overall 5-year survival rate was approximately 69% for aSCC and 49% for rSCC[ 16 ]. However, tumor size has an important impact on disease prognosis[ 17 ]. The larger the tumor, the higher the risk of recurrence and death for patients with aSCC. The patient, in this case, had a giant tumor measuring 19 cm at the time of diagnosis, which to our knowledge, is the largest perianal mass reported thus far. Although the size of the mass decreased after treatment, it can be presumed that the patient's prognosis is poor. This case emphasizes the importance of early detection and early treatment of the disease. List Of Abbreviations HIV Human immunodeficiency virus aSCC anal squamous cell carcinoma HPV human papillomavirus MSM men who have sex with men cART combination antiretroviral therapy MDT Multi-Disciplinary Treatment rSCC rectal squamous cell carcinoma CRT chemoradiotherapy Declarations Ethics approval and consent to participate This study protocol was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of The First Affiliated Hospital, Zhejiang University School of Medicine. Consent for publication Consent for publication was obtained from the patient according to our institutional consent form. Availability of data and materials All data generated or analyzed during this study are included in this published article. Competing interests The authors declare that they have no competing interests to disclose. Funding This work was supported by the National Key R&D Program of China [grant numbers 2021YFC2301900- 2021YFC2301901] and the National Special Research Program for Important Infectious Diseases [grant number 2017ZX10202102]. Authors' contributions XL and GJL provided clinical specimens and information. XL and XLZ performed the data analysis and drafted the manuscript. BZ and XL designed the study. ZKW and YH participated in the study design and coordinated the drafting of the manuscript. All the authors read and approved the final manuscript. References Ciardiello D, Pio Guerrera L, Anna Maiorano B, Parente P, Pia Latiano T, Di Maio M, Ciardiello F, Troiani T, Martinelli E, Maiello E: Immunotherapy in advanced anal cancer: Is the beginning of a new era? Cancer Treat Rev 2022, 105:102373. Rao S, Guren MG, Khan K, Brown G, Renehan AG, Steigen SE, Deutsch E, Martinelli E, Arnold D, [email protected] EGCEa: Anal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up(). Ann Oncol 2021, 32(9):1087–1100. Martini G, Arrichiello G, Borrelli C, Poliero L, Martinelli E: How I treat anal squamous cell carcinoma. ESMO Open 2020, 4(Suppl 2):e000711. McNeil CJ, Lee JS, Cole SR, Patel SA, Martin J, Mathews WC, Moore RD, Mayer KH, Eron JJ, Saag MS et al : Anal cancer incidence in men with HIV who have sex with men: are black men at higher risk? AIDS 2022, 36(5):657–664. Goffredo P, Hassan I: ASO Author Reflections: The Role of Tumor Size in the Prognosis of Anal Squamous Cell Carcinoma: A Validation on the New American Joint Committee on Cancer Subclassification of Stage IIA and B. Ann Surg Oncol 2018, 25(Suppl 3):848–849. Dawson H, Serra S: Tumours and inflammatory lesions of the anal canal and perianal skin revisited: an update and practical approach. Journal of clinical pathology 2015, 68(12):971–981. Trombetta LJ, Place RJ: Giant condyloma acuminatum of the anorectum: trends in epidemiology and management: report of a case and review of the literature. Dis Colon Rectum 2001, 44(12):1878–1886. Abbass MA, Valente MA: Premalignant and Malignant Perianal Lesions. Clin Colon Rectal Surg 2019, 32(5):386–393. Milanes Guisado Y, Sotomayor C, Fontillon M, Dominguez Castano A, Espinosa N, Roca C, Lopez-Cortes LF, Viciana P, Neukam K, Se VSG: Incidence Rate and Risk Factors for Anal Squamous Cell Carcinoma in a Cohort of People Living With HIV from 2004 to 2017: Implementation of a Screening Program. Dis Colon Rectum 2022, 65(1):28–39. Albuquerque A, Nathan M, Cappello C, Dinis-Ribeiro M: Anal cancer and precancerous lesions: a call for improvement. Lancet Gastroenterol Hepatol 2021, 6(4):327–334. Hleyhel M, Hleyhel M, Bouvier AM, Belot A, Tattevin P, Pacanowski J, Genet P, De Castro N, Berger JL, Dupont C et al : Risk of non-AIDS-defining cancers among HIV-1-infected individuals in France between 1997 and 2009: results from a French cohort. AIDS 2014, 28(14):2109–2118. De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S: Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer 2009, 124(7):1626–1636. Stewart DB, Gaertner WB, Glasgow SC, Herzig DO, Feingold D, Steele SR, Prepared on Behalf of the Clinical Practice Guidelines Committee of the American Society of C, Rectal S: The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for Anal Squamous Cell Cancers (Revised 2018). Dis Colon Rectum 2018, 61(7):755–774. Susko M, Wang C-CJ, Lazar AA, Kim S, Laffan A, Feng M, Ko A, Venook AP, Atreya CE, Van Loon K et al : Factors Impacting Differential Outcomes in the Definitive Radiation Treatment of Anal Cancer Between HIV-Positive and HIV-Negative Patients. Oncologist 2020, 25(9):772–779. Chiao EY, Giordano TP, Richardson P, El-Serag HB: Human immunodeficiency virus-associated squamous cell cancer of the anus: epidemiology and outcomes in the highly active antiretroviral therapy era. J Clin Oncol 2008, 26(3):474–479. Astaras C, Bornand A, Koessler T: Squamous rectal carcinoma: a rare malignancy, literature review and management recommendations. ESMO Open 2021, 6(4):100180. Lu Y, Wang X, Li P, Zhang T, Zhou J, Ren Y, Ding Y, Peng H, Wei Q, You K et al : Clinical characteristics and prognosis of anal squamous cell carcinoma: a retrospective audit of 144 patients from 11 cancer hospitals in southern China. BMC Cancer 2020, 20(1):679. Additional Declarations No competing interests reported. Supplementary Files CAREchecklist.pdf Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1916215","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":137473494,"identity":"40515fcb-4402-4b10-96bc-fb2beffe5678","order_by":0,"name":"Xiang Liu","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiang","middleName":"","lastName":"Liu","suffix":""},{"id":137473495,"identity":"46498cf7-2465-4793-ab5f-e225efc949d2","order_by":1,"name":"Xueling Zhu","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xueling","middleName":"","lastName":"Zhu","suffix":""},{"id":137473496,"identity":"28d57720-ab1f-4b7b-9758-50f9c0e90190","order_by":2,"name":"Zhikai Wan","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhikai","middleName":"","lastName":"Wan","suffix":""},{"id":137473497,"identity":"d4a7bde5-712f-4700-9447-ca55451728a9","order_by":3,"name":"Guanjing Lang","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guanjing","middleName":"","lastName":"Lang","suffix":""},{"id":137473498,"identity":"49f200aa-f977-4419-a57b-0545436230a4","order_by":4,"name":"Ying Huang","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Huang","suffix":""},{"id":137473499,"identity":"a980dced-e879-4f3a-9d1b-a2ed4baf59ad","order_by":5,"name":"Biao Zhu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIie3RsUrEQBCA4VkW9pqBtBM4vFcYEGJhIK+yIRCbFNeJYHFVrtmzPtCXsBHLyEKqPEDK2FjZXCNJIyZeZZFL7AT3L4f5mGIAXK6/GIECDYCe9A4N4DDS88jS327OeT7pC7kqAjqOJsjq3gRNcxsi1Dq9aZcWvEXG0D2PE/FQXbAuUxR7XdaEFnzzzmJXjRNJWUBaWZQU5zX3hOuMpcjHifomnxYVJWqtexJNERxInFtELBUUwxWaIETpNcd3KdLCSH+DV0jV2/pld4Ks9snTa/sRRpFFcejM5Zm3TR6b7gT5mTDHZxZzQV/7i12Xy+X6N30Bf9ZJOg8S+8AAAAAASUVORK5CYII=","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Biao","middleName":"","lastName":"Zhu","suffix":""}],"badges":[],"createdAt":"2022-08-01 06:29:16","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.3.rs-1916215/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-1916215/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":26779686,"identity":"41e084ea-6003-488c-944c-3831e8e8b5f1","added_by":"auto","created_at":"2022-09-21 18:03:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13004280,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in treatment of the perianal neoplasm. A. Perianal neoplasm as seen at the initial visit (19×10 cm;) B. The neoplasm shrank after the first cycle of chemotherapy; C Perianal neoplasm after three cycles of chemotherapy.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1916215/v2/6e2df37be3891388fc98fd76.png"},{"id":26779685,"identity":"7c0bdc3e-9856-4964-a007-3a04226d0e6e","added_by":"auto","created_at":"2022-09-21 18:03:30","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":117834,"visible":true,"origin":"","legend":"\u003cp\u003ePET-CT examination of the perianal neoplasms\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1916215/v2/373133f4acf83cac08a89458.jpg"},{"id":26780102,"identity":"479dcb76-e3eb-4db0-a5fd-0a75fd4d6cca","added_by":"auto","created_at":"2022-09-21 18:08:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3376669,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological examination of the perianal neoplasm. A. hematoxylin-eosin stain, ×200; B. P16 positive, ×200.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1916215/v2/1aefe3b3d588ba77e320f729.png"},{"id":31823400,"identity":"8db8a6c6-f280-4fe8-8e34-723870237fe5","added_by":"auto","created_at":"2023-01-19 19:44:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3844510,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1916215/v2/a39855d8-ab1f-4c18-b07c-f7af111ffb57.pdf"},{"id":26779688,"identity":"1b76948d-9494-4829-a89a-c6690b6ea725","added_by":"auto","created_at":"2022-09-21 18:03:31","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":804021,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1916215/v2/87aca445d9413c9540c21873.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Giant Perianal Tumour Arising from Condyloma Acuminatum in a Patient Living with HIV-1","fulltext":[{"header":"Background","content":"\u003cp\u003eMalignant perianal lesions account for only\u0026thinsp;\u0026lt;\u0026thinsp;3% of all gastrointestinal tumors and are therefore considered quite rare[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Its most common histologic variant is squamous cell carcinoma (SCC). The most important causative factor for anal SCC (aSCC) is human papillomavirus (HPV) infection. Other high-risk factors include human immunodeficiency virus (HIV) infection and men who have sex with men (MSM)[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The incidence of anal cancer is higher in HIV-infected than non-HIV-infected patients[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Studies have demonstrated that the larger the tumor, the worse the prognosis of aSCC[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Tumors\u0026thinsp;\u0026gt;\u0026thinsp;5 cm in size were classified as T3. To our knowledge, no relevant literature has reported aSCC with a tumor size\u0026thinsp;\u0026gt;\u0026thinsp;15 cm. Here, we report a case of a giant 19-cm-long aSCC in a male patient who had both HIV and syphilis infection but never received any anti-infective treatment.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 28-year-old homosexual man sought medical attention for a 5-year history of peri-anal condyloma acuminatum that had been rapidly increasing in size for the last several months. He had a 3-year history of HIV infection and syphilis but did not receive combination antiretroviral therapy (cART) and the treatment for syphilis.\u003c/p\u003e \u003cp\u003eThe patient appeared emaciated and had low-grade fever with fatigue at the time of presentation. Physical examination revealed a large, irregular, cauliflower-like, ulcerated mass (19 cm \u0026times; 10 cm) and foul-smelling exudate; the mass covered almost the entire perineum (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Given the exceptionally large size of the tumor and the associated bleeding risk, the patient was unable to maintain a sitting or supine position. Moreover, rectal examination and proctoscopy could not be carried out. Laboratory examination revealed CD4\u003csup\u003e+\u003c/sup\u003e T-cell count was 84 cells/mm\u003csup\u003e3\u003c/sup\u003e, and hemoglobin was 61 g/L. The patient also showed hypoalbuminemia (20 g/L) and hypocholesterolemia (1.92 mmol/L); however, there was no evidence that he was involved in opportunistic infections. Positron-emission tomography\u0026ndash;computed tomography showed that the lesion had invaded and destroyed the surrounding structures of the anorectum and pelvis, and multiple enlarged lymph nodes were found in the groin region (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Pathological analysis and immunohistochemistry indicated SCC with diffuse P16 and Ki-67 expression, and P53 (10%), P40 (+), and P63 (+) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). HPV 31-DNA was detected in the tumor tissue. Chemotherapy combined with radiation therapy was identified as the final treatment scheme after multi-disciplinary treatment (MDT). Albumin-paclitaxel combined with anti-programmed cell death protein 1 (PD-1) therapy and simultaneous antiretroviral therapy was initiated. The lesion began to shrink after the first cycle of chemotherapy (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). After the fifth cycle, local necrosis and hemorrhage of lesions were relieved, and the tumor size finally decreased to 9 cm (length) by 5 cm (base diameter) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). The tumor was temporally controlled by our therapy. Unfortunately, the growth of cancer cells have lost control once again 10 months after diagnosis, and he eventually died from tumor-cachexia at the time of writing this report. Despite the ultimate outcome of this patient would be expected, we believed our treatment successfully extended his lifespan.\u003c/p\u003e"},{"header":"Discussion And Conclusion","content":"\u003cp\u003eWe report a case of SSC from perianal condyloma in a patient who had both HIV and syphilis infection but had never received any anti-infective treatment. We believe that this is the largest perianal mass reported to date. As the tumor was extensively invasive at the time of the patient\u0026rsquo;s presentation, it could not be surgically resected and could only be palliatively treated with chemotherapy combined with radiotherapy. With our treatment, the patient\u0026rsquo;s condition gradually improved, as evidenced by a significant reduction in tumor size, significant relief from hypothermia and fatigue, gradual progress in clinical indicators, and significant enhancement in the quality of life. However, it can be presumed that the patient's overall prognosis is poor.\u003c/p\u003e \u003cp\u003eSuch a large tumor is reminiscent of Buschke\u0026ndash;L\u0026ouml;wenstein tumor or giant condyloma acuminatum, which presents as a large verrucous tumor in the genital area with expansive and destructive growth[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Only 40\u0026ndash;45% of reported cases are diagnosed as simple condyloma acuminatum without invasion, whereas 50\u0026ndash;55% cases show malignant transformation to SCC (verrucous carcinoma variant)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. It is possible that there is a pathological transformation of the condyloma acuminatum to a malignant invasive squamous carcinoma in the presence of high-risk HPV and other risk factors [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. A local pathological biopsy suggested SCC and high-risk HPV infection (P16+) in our patient with history of condyloma acuminatum, which appears to reveal this pathological transformation.\u003c/p\u003e \u003cp\u003eAnal SCC accounts for 90% of all anal tumors, and the incidence of anal margin SCC is 4\u0026ndash;5 times lower than that of anal canal SCC[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The incidence of anal cancer is increasing in certain specific populations such as HIV-infected patients, MSM, women with genital tumors, and patients with condyloma acuminatum or inflammatory bowel disease[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A long-term follow-up study in France confirmed that the risk of anal cancer was highest in HIV-positive and MSM populations, but the risk of anal cancer decreased in the cART era, suggesting the importance of cART in reducing the incidence of non-AIDS-defining tumors[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. HPV infection is the most important risk factor for the development of aSCC. Numerous serotypes of HPV are known, with serotypes 16, 18, 31, 33, and 35 being the most associated with tumors, and serotypes 6 and 11 being the most associated with condyloma acuminata[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Our patient had many risk factors for cancer, such as MSM, untreated HIV infection, untreated condyloma acuminata, and HPV 31 positivity.\u003c/p\u003e \u003cp\u003eAccording to the NCCN Clinical Practice Guidelines in Oncology, version 1.2022, the main treatment for aSCC is chemoradiotherapy (CRT), and the first-line treatment is 5-fluorouracil (5-FU) and mitomycin C (MMC)combined with radiotherapy[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. When multiple metastases are present in the tumor, platinum combined with paclitaxel is recommended for chemotherapy and, if necessary, anti-PD-1/programmed death ligand 1 (PD-L1) immunotherapy[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. HIV-positive aSCC patients with adequate immune reconstitution and virologic suppression can receive a standard CRT regimen, but patients who have uncontrolled HIV-related complications before the diagnosis of aSCC should receive a reduced dose of CRT[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Studies suggest that survival in HIV-positive aSCC patients in the cART era is similar to that of HIV-negative aSCC patients, but there is no evidence to suggest that cART improves survival in HIV-positive aSCC patients[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In addition, stage T1N0M0 aSCC\u0026thinsp;\u0026lt;\u0026thinsp;2 cm in size without lymph node metastases and distant metastases can be surgically resected[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Compared to aSCC, there are no guidelines for the optimal treatment of rectal squamous cell carcinoma( rSCC). Many reports currently support the use of the same CRT approach for rSCC as for aSCC[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In this case, the patient's perianal mass was extremely large and had invaded the rectal and surrounding tissues. After MDT discussion, the patient was treated with albumin paclitaxel combined with anti-PD-1 immunotherapy, and the perianal mass shrank significantly and the clinical indices gradually improved, suggesting that the treatment was effective.\u003c/p\u003e \u003cp\u003eThe overall 5-year survival rate was approximately 69% for aSCC and 49% for rSCC[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, tumor size has an important impact on disease prognosis[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The larger the tumor, the higher the risk of recurrence and death for patients with aSCC. The patient, in this case, had a giant tumor measuring 19 cm at the time of diagnosis, which to our knowledge, is the largest perianal mass reported thus far. Although the size of the mass decreased after treatment, it can be presumed that the patient's prognosis is poor. This case emphasizes the importance of early detection and early treatment of the disease.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eHIV\u0026nbsp; \u0026nbsp; \u0026nbsp;Human immunodeficiency virus\u003c/p\u003e\n\u003cp\u003eaSCC\u0026nbsp; \u0026nbsp;anal squamous cell carcinoma\u003c/p\u003e\n\u003cp\u003eHPV\u0026nbsp; \u0026nbsp;\u0026nbsp;human papillomavirus\u003c/p\u003e\n\u003cp\u003eMSM\u0026nbsp; \u0026nbsp;men who have sex with men\u003c/p\u003e\n\u003cp\u003ecART\u0026nbsp;\u0026nbsp;combination antiretroviral therapy\u003c/p\u003e\n\u003cp\u003eMDT\u0026nbsp; \u0026nbsp;Multi-Disciplinary Treatment\u003c/p\u003e\n\u003cp\u003erSCC\u0026nbsp; \u0026nbsp;rectal squamous cell carcinoma\u003c/p\u003e\n\u003cp\u003eCRT \u0026nbsp; \u0026nbsp;chemoradiotherapy\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study protocol was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of The First Affiliated Hospital, Zhejiang University School of Medicine.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication was obtained from the patient according to our institutional consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Key R\u0026amp;D Program of China [grant numbers 2021YFC2301900- 2021YFC2301901] and the National Special Research Program for Important Infectious Diseases [grant number 2017ZX10202102].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXL and GJL provided clinical specimens and information. XL and XLZ performed the data analysis and drafted the manuscript. BZ and XL designed the study. ZKW and YH participated in the study design and coordinated the drafting of the manuscript. All the authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCiardiello D, Pio Guerrera L, Anna Maiorano B, Parente P, Pia Latiano T, Di Maio M, Ciardiello F, Troiani T, Martinelli E, Maiello E: Immunotherapy in advanced anal cancer: Is the beginning of a new era? Cancer Treat Rev 2022, 105:102373.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRao S, Guren MG, Khan K, Brown G, Renehan AG, Steigen SE, Deutsch E, Martinelli E, Arnold D, [email protected] EGCEa: Anal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up(). Ann Oncol 2021, 32(9):1087\u0026ndash;1100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartini G, Arrichiello G, Borrelli C, Poliero L, Martinelli E: How I treat anal squamous cell carcinoma. ESMO Open 2020, 4(Suppl 2):e000711.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcNeil CJ, Lee JS, Cole SR, Patel SA, Martin J, Mathews WC, Moore RD, Mayer KH, Eron JJ, Saag MS \u003cem\u003eet al\u003c/em\u003e: Anal cancer incidence in men with HIV who have sex with men: are black men at higher risk? \u003cem\u003eAIDS\u003c/em\u003e 2022, 36(5):657\u0026ndash;664.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoffredo P, Hassan I: ASO Author Reflections: The Role of Tumor Size in the Prognosis of Anal Squamous Cell Carcinoma: A Validation on the New American Joint Committee on Cancer Subclassification of Stage IIA and B. Ann Surg Oncol 2018, 25(Suppl 3):848\u0026ndash;849.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDawson H, Serra S: Tumours and inflammatory lesions of the anal canal and perianal skin revisited: an update and practical approach. Journal of clinical pathology 2015, 68(12):971\u0026ndash;981.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTrombetta LJ, Place RJ: Giant condyloma acuminatum of the anorectum: trends in epidemiology and management: report of a case and review of the literature. Dis Colon Rectum 2001, 44(12):1878\u0026ndash;1886.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbbass MA, Valente MA: Premalignant and Malignant Perianal Lesions. Clin Colon Rectal Surg 2019, 32(5):386\u0026ndash;393.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMilanes Guisado Y, Sotomayor C, Fontillon M, Dominguez Castano A, Espinosa N, Roca C, Lopez-Cortes LF, Viciana P, Neukam K, Se VSG: Incidence Rate and Risk Factors for Anal Squamous Cell Carcinoma in a Cohort of People Living With HIV from 2004 to 2017: Implementation of a Screening Program. Dis Colon Rectum 2022, 65(1):28\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlbuquerque A, Nathan M, Cappello C, Dinis-Ribeiro M: Anal cancer and precancerous lesions: a call for improvement. Lancet Gastroenterol Hepatol 2021, 6(4):327\u0026ndash;334.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHleyhel M, Hleyhel M, Bouvier AM, Belot A, Tattevin P, Pacanowski J, Genet P, De Castro N, Berger JL, Dupont C \u003cem\u003eet al\u003c/em\u003e: Risk of non-AIDS-defining cancers among HIV-1-infected individuals in France between 1997 and 2009: results from a French cohort. AIDS 2014, 28(14):2109\u0026ndash;2118.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S: Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer 2009, 124(7):1626\u0026ndash;1636.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStewart DB, Gaertner WB, Glasgow SC, Herzig DO, Feingold D, Steele SR, Prepared on Behalf of the Clinical Practice Guidelines Committee of the American Society of C, Rectal S: The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for Anal Squamous Cell Cancers (Revised 2018). Dis Colon Rectum 2018, 61(7):755\u0026ndash;774.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSusko M, Wang C-CJ, Lazar AA, Kim S, Laffan A, Feng M, Ko A, Venook AP, Atreya CE, Van Loon K \u003cem\u003eet al\u003c/em\u003e: Factors Impacting Differential Outcomes in the Definitive Radiation Treatment of Anal Cancer Between HIV-Positive and HIV-Negative Patients. Oncologist 2020, 25(9):772\u0026ndash;779.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiao EY, Giordano TP, Richardson P, El-Serag HB: Human immunodeficiency virus-associated squamous cell cancer of the anus: epidemiology and outcomes in the highly active antiretroviral therapy era. J Clin Oncol 2008, 26(3):474\u0026ndash;479.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAstaras C, Bornand A, Koessler T: Squamous rectal carcinoma: a rare malignancy, literature review and management recommendations. ESMO Open 2021, 6(4):100180.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu Y, Wang X, Li P, Zhang T, Zhou J, Ren Y, Ding Y, Peng H, Wei Q, You K \u003cem\u003eet al\u003c/em\u003e: Clinical characteristics and prognosis of anal squamous cell carcinoma: a retrospective audit of 144 patients from 11 cancer hospitals in southern China. BMC Cancer 2020, 20(1):679.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"perianal cancers, squamous cell carcinoma, Human immunodeficiency virus, Giant","lastPublishedDoi":"10.21203/rs.3.rs-1916215/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1916215/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePerianal cancer is a relatively rare disease, but it is prevalent in men who have sex with men and in patients who are positive for human immunodeficiency virus (HIV). Here, we report a case of a massive anal squamous cell carcinoma that measured 19 cm in length and 10 cm in diameter in a male patient living with HIV.\u003c/p\u003e\u003ch2\u003eCase presentation\u003c/h2\u003e \u003cp\u003eA 28-year-old man with a 5-year history of peri-anal condyloma acuminatum developed a rapidly enlarging mass in the anal region since the past few months. He had both HIV and syphilis infection, but never sought further treatment. Pathological analysis and immunohistochemistry confirmed squamous cell carcinoma with high-risk HPV infection. After multi-disciplinary treatment, albumin-paclitaxel combined with anti-programmed cell death protein 1 therapy and simultaneous antiretroviral therapy was initiated. The mass began to shrink after chemotherapy, but this did not prevent tumor progression. He eventually died from tumor-cachexia.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eEarly screening and treatment of perianal disease can help prevent progression to invasive anal carcinoma in high-risk groups such as men who have sex with men and immunosuppressed patients.\u003c/p\u003e","manuscriptTitle":"Giant Perianal Tumour Arising from Condyloma Acuminatum in a Patient Living with HIV-1","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2022-09-21 18:03:28","doi":"10.21203/rs.3.rs-1916215/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2022-08-08 17:58:52","doi":"10.21203/rs.3.rs-1916215/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b29b3d16-e9a9-4fb9-b79b-4105baf40b91","owner":[],"postedDate":"September 21st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-01-19T19:44:15+00:00","versionOfRecord":[],"versionCreatedAt":"2022-09-21 18:03:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-1916215","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1916215","identity":"rs-1916215","version":["v2"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}