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Case Study Clinical Case Reports International Published: 15 Jun, 2020

Highlighting the Importance of Sexually Transmitted Disease Testing Upon Diagnosis of Penile : A Case Report

Médina Ndoye1, Lissoune Cisse1, Mark LaGreca2, Timothy Phillips2, Mark Siden2* and Matthew Weaver2 1Department of Urology, Idrissa Pouye General Hospital, Senegal

2Department of Medicine, Philadelphia College of Osteopathic Medicine, USA

Abstract There is a well-known association between Human Papillomavirus and Human Immunodeficiency with penile cancer. Yet, it is not the standard of care to screen for either of these sexually transmitted diseases upon diagnosis of primary penile cancer. We present a 50 year old male who had a confirmed diagnosis of penile cancer for 2 years prior to his presentation to our clinic in Dakar, Senegal. Outside institutions repeatedly failed to screen the patient for sexually transmitted diseases, namely HPV and HIV. We share this case to emphasize the importance of sexually transmitted disease upon diagnosis of penile cancer with hopes to increase awareness in both developed and developing nations. We call for consensus in sexually transmitted disease screening guidelines upon penile cancer diagnoses. Keywords: Penile cancer; HPV; HIV; STD screening

Introduction Primary penile cancer is a rare malignant overgrowth of cells, typically located on the glans or the internal prepuce of the . It has a worldwide of 1/100,000 and most commonly affects males between the ages of 50 years to 70 years. Delayed diagnosis often yields significant OPEN ACCESS morbidity and mortality [1,2]. While penile cancer is uncommon in Europe and North America, the developing world has much higher rates of incidence up to 8 cases per 100,000 in some countries *Correspondence: [3]. Variations in incidence worldwide are hypothesized to be affected by socioeconomic status, Mark Siden, Department of Medicine, healthcare accessibility, cultural tradition, and psychological factors of the patient populations [1,4]. Philadelphia College of Osteopathic Over 95% of penile carcinomas are Squamous Cell in Carcinoma (SCC) [1]. Additionally, there Medicine, Philadelphia, USA, Tel: +01- are a wide variety of other histological variants, such as basaloid, verrucous, and sarcomatoid [3]. 9144098791; The majority of lesions are found on the glans (48%), with the remainder located on the prepuce E-mail: [email protected] (21%), both glans and prepuce (15%), coronal sulcus (6%), and shaft (<2%) [4]. Diagnosis is often Received Date: 14 May 2020 clinical, though clinical presentation is variable and commonly asymptomatic initially. Lesions Accepted Date: 10 Jun 2020 can present as indurated nodules, ulcers, or fun gating masses. With progression, symptoms such Published Date: 15 Jun 2020 as itching, bleeding, discharge, or pain may occur. Advanced disease can present with palpable Citation: lymphadenopathy, weight loss and fatigue [5]. Ndoye M, Cisse L, LaGreca M, Phillips Certain biological pathologies have been tied to increased incidence. Poor , uncircumcised T, Siden M, Weaver M. Highlighting the males, urethral stricture, use, and even psoralen A photochemotherapy have all Importance of Sexually Transmitted been associated with increased penile cancer incidence in prior studies [6]. Chronic Disease Testing Upon Diagnosis of may also be a critical component of tumor development, as many penile arise from sites Penile Cancer: A Case Report. Clin of infection, chronic irritation or injury [1]. Further, penile cancer is best known to have a strong Case Rep Int. 2020; 4: 1163. association with carcinogenic strains of Human Papillomavirus (HPV). For example, HPV infection Copyright © 2020 Mark Siden. This is is found in 45% to 80% [5] of penile SCC cases. This association is even higher in other histological an open access article distributed under types such as verrucous, basaloid and sarcomatoid [7]. The most commonly accepted explanation for the Creative Commons Attribution the association is HPV’s ability to produce the oncogenic proteins E6 and E7, which interfere with License, which permits unrestricted the p53 and Retinoblastoma tumor suppressor genes, respectively [8]. This carcinogenic mechanism use, distribution, and reproduction in is especially important in populations with high HPV infection rates, such as Sub-Saharan Africa. any medium, provided the original work HPV incidence was found to be around 61% of the male population in Sub-Saharan Africa in 2012 [13]. Human Immunodeficiency Virus (HIV) may also play a role in SCC pathogenesis. Though a is properly cited.

Remedy Publications LLC., | http://clinicalcasereportsint.com/ 1 2020 | Volume 4 | Article 1163 Mark Siden, et al., Clinical Case Reports International - Medicine causal link between immunosuppression and penile oncogenesis has not yet been made, men who are HIV+ carry up to an 8X greater risk of penile SCC [5,9]. Despite HPV and HIV’s well known association with penile cancer, there is a serious lack of attention to the preventive health component of this condition. For example, the European Urological Association’s (EUA) guidelines for penile cancer address diagnostic standards, staging, and possible treatment avenues that individual cases may necessitate. However, there is little acknowledgement of the public health risks that penile cancer may pose with an underlying HPV and HIV infection. Additionally, there seems to be no recommendation for penile cancer management specifically in developing nations, including Sub-Saharan Africa, which may have unique socioeconomic roadblocks. Consequently, this case report aims to emphasize the critical importance of screening for HIV/HPV upon a diagnosis of penile cancer, such that it should be included in official penile cancer guidelines. Prompt evaluation of a patient’s STD status can not only decrease morbidity and mortality for the patient, but also provide preventative measures against future HPV-related cancers, as well as HIV complications in the community. Figures 1 and 2: Urogenital exam revealed an ulcer of 8 cm of long axis of Case Presentation the penis enveloping the glans and the proximal 2/3 of the penis with a clean We present a 50 year-old Senegalese male with a history of bottom. He had inflammation of the 2 bursa, and a penoscrotal fistula from which pus drained. There were hard and painful inguinal lymphadenopathies recurrent , who presented to our clinic for an evolving bilaterally. A urinary catheter in place drained cloudy urine. ulcerative swelling on his penis for the past 2 years. The patient’s medical history is limited secondary to lack of documentation and and suggests that a diagnosis of HIV may worsen the prognosis of the resources from outside institutions. The patient had presented to disease. Additionally, Konan recommends screening HIV+ patients several local clinics before the diagnosis of penile cancer was made; for penile cancer so that tumors can be discovered in earlier stages. those records were unable to be obtained. The patient received 12 Patients would therefore be more likely to be treated conservatively. sessions before being referred to our clinic. Of note, the As for HPV, there is evidence to suggest that good clinical suspicion patient was polygamous with 2 wives, though became divorced since to screen for the virus in sexually active patients may reduce the risk the beginning of the disease. He did not report having unprotected of subsequent oropharyngeal cancers in the public [12,13]. Hence, it intercourse with other women. may be extrapolated that early diagnosis of these may prevent CT scans demonstrated local invasion of the cancer into the their transmission and subsequent complications in the community. subcutaneous fat overlying the pubic symphysis. Despite the plethora of information on the internet, there is still metastases with left inguinal necrotic lymphadenopathy of 5 cm were not enough consistent information to educate developing nations on also present. Furthermore, there were bilateral, multiple lung nodules the infectious disease management of penile cancer. For example, the of different sizes, mostly predominant on the left side. EUA never recommends screening for HPV/HIV in penile cancer The patient never received an STD screening since his diagnosis. patients and the American Urologic Association has no specific We performed an HIV and HPV test that came back positive for guidelines for penile cancer whatsoever. Consequently, Teh et al. HIV2, previously unknown to the patient. The results also came back [2] was right to describe finding consistent information on penile HPV (+) for serotype 16. As of May 2020, the patient is currently alive cancer as a “needle in the haystack”. Additionally, they state that and being treated accordingly. there seems to be a discrepancy in the quality of websites in differing languages, with significantly lesser quality available in the developing Discussion world. With all of the inconsistencies in literature, the severity of our There are no written recommendations for STD screening in patient’s case could have been prevented by access to clear, concise patients diagnosed with penile cancer despite overwelming evidence STD recommendations. that there is some association between HIV, HPV and penile cancer Necessarily, we call for specific, evidenced-based recommendations [10,11]. Evidenced by our patient remaining undiagnosed with HIV2 for STD testing for penile cancer diagnosis. A clear consensus would after initial presentation 2 years ago, delay in STD diagnosis can have address the discrepancies and current confusion across resources. For dire consequences. An earlier diagnosis for our patient may have our future patients and the entire medical community, we seek more prevented the eventual progression of his penile cancer and further thorough guidelines in regards to testing for HIV and HPV upon a metastatic disease. diagnosis of penile cancer. We hypothesize that early diagnosis of HPV and HIV infections Conclusion in patients can have a marked benefit for public health as well. With earlier identification and Highly Active Anti-Retroviral Therapy The association between penile cancer, HPV, and HIV has been (HAART), HIV transmission will likely decrease. A case report written well established. However, in the developing world, it is not always by Konan et al. acknowledges a link between HIV and penile cancer common practice to properly screen for STDs upon a diagnosis of

Remedy Publications LLC., | http://clinicalcasereportsint.com/ 2 2020 | Volume 4 | Article 1163 Mark Siden, et al., Clinical Case Reports International - Medicine penile cancer. Prompt screening of these patients can lead to earlier 7. Rubin MA, Kleter B, Zhou M, Ayala G, Cubilla AL, Quint WGV, et al. treatment, better outcomes, increased public health awareness, and Detection and typing of human papillomavirus DNA in penile carcinoma: potential for more cost effective care. Thus, screening for sexually Evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol. 2001;159(4):1211-8. transmitted diseases should be the standard of care in anyone diagnosed with penile cancer. 8. kayes O, Ahmed Hu, Arya M, Minhas S. Molecular and genetic pathways in penile cancer. Lancet Oncol. 2007;8(5):420-9. References 9. Konan PG, Vodi CC, Dekou AH, Fofana A, Gowé EE, Manzan K. Cancer 1. Bleeker MCG, Heideman DAM, Snijders PJF, Horenblas S, Dillner J, of the penis associated with HIV: A report of three cases presenting at the Meijer CJLM. Penile cancer: Epidemiology, pathogenesis and prevention. CHU cocody, ivory coast. BMC Urol. 2015;15:112. World J Urol. 2009;27(2):141-50. 10. Théodore C, Androulakis N, Spatz A, Goujard C, Blanchet P, Wibault P. 2. Teh J, Op’tHoog S, Nzenza T, Duncan C, Wang J, Radojcic M, et al. Penile An explosive course of squamous cell penile cancer in an AIDS patient. cancer information on the internet: A needle in a haystack. BJU Int. Ann Oncol. 2002;13(3):475-9. 2018;122(Suppl 5):22-6. 11. Kristiansen S, Svensson A, Drevin L, Forslund O, Torbrand C, Bjartling 3. Hakenberg OW, Dräger DL, Erbersdobler A, Naumann CM, Jünemann C. Risk factors for penile intraepithelial neoplasia: A population-based KP, Protzel C. The diagnosis and treatment of penile cancer. Dtsch Arztebl register study in Sweden, 2000-2012. Acta Derm Venerol. 2019;99(3):315- Int. 2018;115:646-52. 20. 4. Mehmet S, Ersan B. Penile Cancer: Case Report. Int Arch Urol Complic. 12. Martin-Hernan F, Sanchez-Hernandez JG, Cano J, Campo J, del Romero J. 2018;4(2). Oral cancer, HPV infection and evidence of sexual transmission. Med Oral Patol Oral Cir Bucal. 2013;18(3):e439-44. 5. Clark PE, Spiess PE, Agarwal N, Biagioli MC, Eisenberger MA, Greenberg RE, et al. Penile Cancer: Clinical practice guidelines in . Natl 13. de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of Compr Canc Netw. 2013;11(5):594-615. cancer attributable to HPV by site, country and HPV type: Worldwide burden of cancer attributable to HPV. Int J Cancer. 2017;141(4):664-70. 6. Dillner J, Krogh G von, Horenblas S, Meijer CJ. Etiology of of the penis. Scand J Urol Nephrol Suppl. 2000;34(205):189-93.

Remedy Publications LLC., | http://clinicalcasereportsint.com/ 3 2020 | Volume 4 | Article 1163