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1.
PLoS One ; 19(5): e0300729, 2024.
Article in English | MEDLINE | ID: mdl-38691575

ABSTRACT

Penile squamous cell carcinoma (PSCC) occurs more frequently in some developing countries compared to developed countries. Infection with HIV and/or high-risk human papillomavirus (hrHPV) are risk factors for penile cancer development. The tumor microenvironment of PSCC may predict prognosis and may inform on the best targets for immunotherapy. We evaluated the immune microenvironment of penile tumors histologically, and determined whether and/or how HIV and/or hrHPV infections affect this tumor microenvironment. We conducted a prospective analytical cross-sectional study in which penile cancer tumors from 35 patients presenting at the University Teaching Hospital in Lusaka, Zambia were histologically staged and assessed for presence of tumor infiltrating immune cells and expression of immune checkpoints. Immunohistochemistry was used to evaluate immune checkpoints and infiltrating immune cells, while multiplex real-time polymerase chain reaction was used for hrHPV genotyping. The median age of all participants was 55 years. About 24% had advanced histological stage, 83% were HIV+, and 63% had hrHPV detected in their tumors using multiplex real-time polymerase chain reaction. PDL1 expression was significantly higher in HIV- participants than HIV+ participants (p = 0.02). Tumors with multiple hrHPV infections had a significantly higher number of cells expressing TIM3 than those with one hrHPV (p = 0.04). High grade tumors had a significantly higher infiltrate of FoxP3+ cells (p = 0.02), CD68+ cells (p = 0.01), CD163+ cells (p = 0.01), LAG3+ cells (p = 0.01), PD1+ cells (p = 0.01) and TIM3+ cells (p = 0.03) when compared with low grade tumours. There was significant moderate to strong positive correlation of cells expressing PD1 and LAG3 (⍴ = 0.69; p = 0.0001), PD1 and TIM3 (⍴ = 0.49; p = 0.017) and TIM3 and LAG3 PDL1 (⍴ = 0.61; p = 0.001). In conclusion, the tumor microenvironment of penile squamous cell carcinoma seems to be affected by both HIV and HPV infections. TIM3 appears to be a potential therapeutic target in PSCC patients with hrHPV infections.


Subject(s)
Carcinoma, Squamous Cell , HIV Infections , Papillomavirus Infections , Penile Neoplasms , Tumor Microenvironment , Humans , Male , Tumor Microenvironment/immunology , Penile Neoplasms/virology , Penile Neoplasms/pathology , Penile Neoplasms/immunology , Carcinoma, Squamous Cell/virology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Middle Aged , HIV Infections/immunology , HIV Infections/complications , HIV Infections/virology , HIV Infections/pathology , Papillomavirus Infections/immunology , Papillomavirus Infections/virology , Papillomavirus Infections/complications , Papillomavirus Infections/pathology , Cross-Sectional Studies , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Aged , Papillomaviridae , Adult , Prospective Studies , Lymphocytes, Tumor-Infiltrating/immunology , Human Papillomavirus Viruses
2.
BJU Int ; 129(4): 434-441, 2022 04.
Article in English | MEDLINE | ID: mdl-35128806

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has brought about many changes in the relationships between high-income countries and partner organisations in low- or low-middle-income countries, such as predominate in sub-Saharan Africa. Medicine, surgery and in particular urology is no exception to the changes that COVID-19 has demanded. Urolink represents the British Association of Urological Surgeons (BAUS) on the global urology stage and has been deleteriously impacted by the pandemic. Education, one of the pillars of Urolink's founding philosophies, has conventionally been delivered by face-to face teaching, training, or mentoring by UK urologists at their host's site outside of the UK. As a consequence of the inability to travel due to the pandemic, BAUS Urolink has evolved a virtual on-line webinar package evolved by, and delivered between, urologists in Lusaka, Zambia, and various centres in the UK. The aim was to deliver curricular-based educational topics to trainees in both countries. This programme has generated a number of live webinars and archived recordings during the pandemic that has proven accessible and educationally acceptable to trainees in the UK and Zambia. This webinar series has also generated relationships between young urologists on different continents, given each a different view of healthcare delivery outside of their country of origin at no appreciable cost, and would appear to be an educational mechanism that is durable for, and applicable to, a wider participation in the post-pandemic world.


Subject(s)
COVID-19 , Education, Distance , COVID-19/epidemiology , Developed Countries , Humans , SARS-CoV-2 , Zambia
3.
PLoS One ; 11(6): e0156265, 2016.
Article in English | MEDLINE | ID: mdl-27253372

ABSTRACT

OBJECTIVE: Medical device use is currently approved for males without preputial or major penile scrotal abnormalities for voluntary medical male circumcision (VMMC). We determined the prevalence of preputial abnormalities at a busy VMMC centre in Soweto, South Africa. METHODS: This was a cross-sectional record review at a high-volume VMMC centre in South Africa. We collated pre-circumcision demographic and genital examination findings from clients 8 years and older who had undergone VMMC from 01 May 2013 to 30 April 2014. Logistic regression was used to determine factors associated with preputial abnormalities. FINDINGS: During the review period, 6861 circumcisions were conducted and 37.1% (n = 2543) were 8-13 year olds. Median age was 15 years (IQR: 12-23 years). Fifteen percent (n = 1030) had preputial abnormalities or major penile scrotal abnormalities. Age-specific prevalence of preputial or major genital abnormalities were 27.3%, 10.6% and 6.0% in 8-13, 14-18 and > 18 year olds respectively. The odds of preputial or major penile scrotal abnormality were higher in younger clients aged 8-13 years (OR = 5.9; 95% CI = 4.8-7.1) and 14-18 years (OR = 1.9; 95% CI = 1.5-2.4) compared to older clients above18 years and in those testing for HIV outside our clinic network (OR = 1.9; 95% CI = 1.4-2.7). CONCLUSION: The high prevalence of preputial and penile scrotal abnormalities observed suggests a need for VMMC sites to provide for both open surgical and devices methods in the provision of VMMC services. This is especially so among young male subjects presenting themselves for VMMC services at the various sites being developed in sub Saharan African countries.


Subject(s)
Circumcision, Male , Foreskin/surgery , Genital Diseases, Male/surgery , Penis/surgery , Adolescent , Adult , Child , Cross-Sectional Studies , Foreskin/physiopathology , Genital Diseases, Male/epidemiology , Genital Diseases, Male/physiopathology , HIV/pathogenicity , Humans , Male , Penis/abnormalities , Penis/physiopathology , South Africa/epidemiology , Young Adult
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