Penile Squamous Cell Carcinomas in Sub-Saharan Africa and Europe: Differential Etiopathogenesis

Abstract

Penile squamous cell carcinomas (PSCC) are classified by the World Health Organization into two categories based on their relationship with the human papillomavirus (HPV): HPV-associated and HPV-independent. We compared a cohort of PSCC from Mozambique, a sub-Saharan country in southeast Africa with a high prevalence of HPV and HIV infection, and Spain, a country in southwestern Europe with a low prevalence of HPV and HIV, to study the distribution of the etiopathogenic categories of these tumors in both sites. A total of 79 PSCC were included in the study (28 from Mozambique and 51 from Spain). All cases underwent HPV-DNA polymerase chain reaction (PCR) testing, genotyping, and immunohistochemistry for p16 and p53. Any PSCC showing either p16 overexpression or HPV-DNA in PCR analysis was considered HPV-associated. Overall, 40/79 (50.6%) tumors were classified as HPV-associated and 39 (49.4%) as HPV-independent. The two sites showed marked differences: 25/28 (89.3%) tumors from Mozambique and only 15/51 (29.4%) from Spain were HPV-associated (p < 0.001). HPV16 was the most frequent HPV type identified in 64.0% (16/25) of the HPV-associated tumors from Mozambique, and 60.0% (9/15) from Spain (p = 0.8). On average, patients from Mozambique were almost two decades younger than those from Spain (mean age 50.9 ± 14.9 and 69.2 ± 13.3, respectively [p < 0.001]). In conclusion, significant etiopathogenic differences between PSCC in Mozambique and Spain were observed, with a remarkably high prevalence of HPV-associated tumors in Mozambique and a relatively low prevalence in Spain. These data may have important consequences for primary prevention of PSCC worldwide.

p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas with Adverse Prognosis

“…These results suggest that, as shown in HPV-associated tumors from other anatomical areas, HPV-associated PSCC is highly sensitive to radiation and chemotherapy [26]. In accordance with the findings of other European series [27], HPV-associated tumors represented a small percentage (29.5%) of all PSCC, which is in contrast with the findings of studies from sub-Saharan Africa or the Caribbean, which showed rates of HPV-associated PSCC as high as 80% [28]. As previously reported, p16 IHC results have shown excellent correlation with HPV ISH [29], reinforcing the validity of the recent WHO 2022 recommendation of using p16 IHC as a surrogate for the presence of high-risk HPV [22].…”

P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation

“…DNA extraction was performed on 10-µm whole tissue sections using a commercial kit (QIAamp DNA FFPE Tissue Kit; Qiagen, Hilden, Germany) as previously described [24]. HPV DNA genotyping was performed using the short polymerase chain reaction (PCR) fragment (SPF10) amplified through the INNO-LiPA HPV Genotyping Extra II Amplification (Fujirebio, Gent, Belgium) [25].…”

The effects of HIV and oncogenic human papillomavirus on the tumor immune microenvironment of penile squamous cell carcinoma

“…HPV-associated PSCCs are more common in SSA countries where the incidence of the malignancy is high. Patients in these countries present at a much younger age than patients in first-world countries where the incidence is much lower [ 8 ]. In addition, most patients in SSA present with advanced disease, and a majority are infected with the Human Immunodeficiency Virus (HIV) [ 9 ].…”