With 1.7 million new infections each year, there are over 38 million individuals living with HIV worldwide. ¹ HIV primarily affects the immune system, especially concentrating on dendritic cells, mononuclear macrophages, and CD4+T lymphocytes. As a result, the number of CD4+T cells continues to decline, the blood HIV viral load is noticeably high, and symptoms including fever, lymphadenopathy, sore throat, myalgias/arthralgias, headaches, and mucocutaneous ulcerations are among those that are manifested. When cellular immunity is severely compromised, several opportunistic infections and tumors may eventually occur. The life expectancy of HIV patients has been markedly extended due to the widespread use of high-efficiency combination anti-retroviral therapy (ARV), and the prevalence of illnesses that coexist with HIV has steadily grown. ^{2 , 3}

A malignant development called urothelial carcinoma (UC) damages the lining of the urinary canal from the renal pelvis to the distal urethra. Urothelial carcinoma can invade the basement membrane, lamina propria, or deeper by neoplastic cells of urothelial origin. ⁴ Urothelial carcinoma is less prevalent throughout the upper urinary system (renal pelvis and ureter), where it accounts for 5–10% of cases, and much less common—less than 1%—along the urethra. ⁵ The absence of a definite consensus on how to treat this illness is explained by the rarity of urethral cancer. ⁶

While Kaposi sarcoma and non-Hodgkin lymphomas are well-known HIV-related cancers, the connection between HIV and urinary cancers is still unclear. The relationship between urothelial cancer and HIV infection looked like a worthwhile issue for research, especially since HIV invades CD4 + T cells and impairs the immune system. ⁷ Until now, case reports regarding primary urethral carcinoma cases in HIV patients are still very rare. Therefore, in this study, we report a case of Urethral Urothelial Carcinoma in HIV patient who underwent total urethrectomy and perineal urethrostomy.

A 34-year-old male patient came with complaints of a papilliferous lump on the glans penis for more than 6 months before being admitted for the first time to the hospital. The lump bleeds easily if it rubs against the trousers ( Figure 1). The patient is known to have a history of having sex with members of the same sex. The patient’s history of hematuria was denied. The results of the preoperative screening showed that the patient had HIV.

The patient then underwent urethrocystoscopy surgery. Urethral mass was found up to the midshaft penile urethra ( Figure 2). Then, it was decided that the patient’s treatment was a partial urethrectomy with tumor-free margins neo-external urethral meatus was positioned in the proximal urethra area near the penoscrotal junction ( Figure 3). The result of pathological evaluation of the mass was high grade papillary urothelial carcinoma. Patients then decided to undergo routine post-operative follow-up examinations. Patients also routinely undergo control at the internal medicine department for ARV therapy.

Five months after surgery, the patient came with recurrent papillary lump that on the neourethral stump and spread to the distal skin and glans penis ( Figure 4). The patient then underwent another total urethrectomy operation, TUR of the mass in the prostatic urethra near the verumontanum, and perineal urethrostomy ( Figures 5- 7).

After the development of efficient antiretroviral therapy (ARV) in 1996, the risk for AIDS and mortality in HIV-infected individuals significantly decreased. ^{1 , 8} Although it has decreased in the ARV era, the incidence of cancer among HIV-infected patients is much higher than in the normal population. People with HIV are presently roughly 500 times more likely to have a Kaposi sarcoma diagnosis than the general population, 12 times more likely to receive a non-Hodgkin lymphoma diagnosis, and, among women, three times more likely to receive a cervical cancer diagnosis. ^{9 , 10}

To date, the connection between HIV and urinary cancers is still unclear. HIV infection is known to impair the immune system and lower the body’s capacity to combat viral infections that may cause cancer. This means that pre-cancerous lesions in the body are not properly detected. In addition, the increase in cancer prevalence in HIV patients is suspected to be related to the increase in viral infection rates. ¹¹ Because HIV-positive individuals have impaired immune systems, immunosuppression, and inflammation may have direct or indirect roles in the occurrence of various malignancies that are more common in HIV-positive individuals. In terms of malignancies other than those that are indicative of AIDS, a study found that HIV-positive Koreans had a much greater incidence of cancers brought on by viral infections. Investigations into the hypothesis that human papillomavirus (HPV) infection is a risk factor influencing the development of urothelial cancer have not shown any conclusive results.7 Additionally, there is a greater incidence of several conventional risk factors for cancer among HIV-positive individuals, including smoking (which is known to cause lung and other cancers) and heavy alcohol consumption (which can raise the risk of liver cancer). ^{10 , 12}

Case reports regarding the incidence of urothelial cancer in HIV patients are still very rare. Although it’s still an uncommon occurrence, just 0.2% of persons with HIV get bladder cancer, according to research conducted in Paris. This cohort’s estimated five-year partial prevalence of bladder cancer (2004–2008) was 128.1 per 100,000 people, which was comparable to the French general male population’s rate. However, compared to other cancers in this population, such as Kaposi sarcoma and non-Hodgkin lymphomas, which have been reported to have ten-fold higher prevalence rates, and lung and anal cancers, which have been reported to have an average 5-fold higher prevalence rate in 2006 in France, urological cancer is still much less common in HIV-infected patients. In fact, there are just a few case reports in the literature. ⁷

As one of the rarest cancers of the urogenital tract is primary carcinoma of the urethra. According to estimates, the incidence rate is 1.1 per million people and peaks after age 75. The signs of growing cancer are non-specific and might be mistakenly attributed to other lower urinary tract obstructive conditions. Patients most frequently describe haematuria and symptoms related to lower urinary tract blockage. Extraurethral mass, irritative sensations, and pelvic pain are other signs. In this case the patient had no history of hematuria but presented with complaints of a period that bleeds easily. ¹³ Chronic inflammation, urethritis history, and urethral stricture are the primary risk factors. Other, less common causes, such urethroplasty, intermittent urethral catheterization, external pelvic irradiation, and brachytherapy, have been implicated. It is important to keep in mind that several traditional risk factors for bladder cancer, such smoking, may not necessarily be connected to the development of urethral cancer. ⁶

Until now, case reports regarding primary urethral carcinoma cases in HIV patients are still extremely rare. Some conditions of urothelial cancer need surgery as a treatment option. Regarding primary urethral carcinoma therapy, there is currently no agreement. Most of the time, treatment is tailored specifically to the patient based on the location, histology, and stage of the carcinoma. Aggressive excisional surgery was used to treat tumours of the anterior urethra in a manner similar to how tumours of the penis were treated. A large, healthy surgical margin was deemed required in order to provide acceptable local control, which was the major objective. ¹⁴ According to the European recommendations for the therapy of primary urethral cancer, localised anterior tumours (p T1-3) should be treated conservatively with a penile-preserving urethrectomy. Patients who have lymph node involvement in the iliac or inguinal regions (N1, N2) may even be recommended this conservative approach in conjunction with lymph node dissection. ¹⁵

An operation to remove all or a portion of the male urethra is known as a urethrectomy. Patients with UC at high risk may occasionally be candidates for this surgery as in this case. ^{16 , 17} This patient also underwent a surgical procedure called a perineal urethrostomy to make a permanent incision in the perineum’s skin through which the urethra may be accessed. This procedure is carried out to overcome the urinary passage challenge after total urethrectomy. Perineal urethrostomies are most frequently performed using the Blandy method. It entails producing a perineum incision (cut) in the shape of an inverted U immediately below the scrotum. The bulbar urethra is exposed when the skin is split apart, and a three- to four-centimeter-long incision is made into it along its length. The closest portion of the opening urethra is joined by suturing (sewing) the upper portion of the perineal flap of skin. Additionally, the perineal flap’s margins are stitched to the urethral mucosa’s borders. The urethral opening is then finished by sewing the scrotal skin to the top portion of the aperture up to the perineal flap. After the procedure, a Foley catheter is inserted via the urethrostomy into the bladder to remove urine from the body. ^{18 , 19}

Making surgical decisions when a patient has HIV infection might be an issue. HIV infection has an impact on life expectancy, nutritional state, and the differential diagnosis of surgical diseases. HIV infection may, according to some, also affect surgical wound healing and complication rates. ^{20 , 21} As part of the preoperative examination for patients with HIV, doctors should evaluate the most current CD4 cell count and HIV viral load test findings. Retesting prior to surgery is not essential if current test results (6 months for HIV viral load; 12 months for CD4 count) are accessible in the patient’s medical records. In general, surgical mortality and complications are more likely to occur in HIV patients who have low CD4 counts and uncontrolled viral loads. A skilled HIV care provider should be consulted if surgery is planned and the patient has a viral load level or CD4 count of 200 copies/mL or less. ²¹

Patients with HIV are more likely to develop venous thrombosis than people without HIV. Therefore, it is crucial to start pharmacologic prophylaxis and mobilize HIV patients as soon as medically possible following surgery. The stress of surgery can reveal hypoadrenalism in those with a long history of HIV, low CD4 counts, or exposure to boosted regimens and glucocorticoids. When evaluating postoperative hypotension, this possibility should be considered. Prioritizing common causes of fever, such as urinary tract infections, pneumonia, venous thromboembolism, wound infections, or Clostridioides difficile if antibiotics were given, should be done in patients with HIV and postoperative fever before HIV-related reasons. Clinicians should visit an infectious disease expert if the patient’s CD4 count is less than 200 cells/mm ³. ^{21 – 23}

HIV infection is known to impair the immune system and lower the body’s capacity to combat viral infections that may cause cancer. As one of the rarest cancers of the urogenital tract, case of primary carcinoma of the urethra in HIV patient is extremely rare. To date, treatment of primary urethral carcinoma is tailored specifically to the patient based on the location, histology, and stage of the carcinoma.

Ethical approval not required.

Written informed consent for the publication of the case report and any associated images obtained from the patient.