Penile squamous cell carcinoma (PSCC) can be classified into human papilloma virus-positive (HPV⁺) and HPV-independent (HPV^–). HPV⁺ tumours have higher rates of poorly differentiated disease than HPV^– tumours. However, a lower cancer-specific mortality (CSM) has been reported in patients with HPV⁺ versus HPV^– disease. This evidence might be partially explained by a disproportionate occurrence of loss-of-function mutations of TP53 (TP53LOF) in patients with HPV^– versus HPV⁺ disease.

In a study published in European Urology, a PSCC single-cell RNA sequencing (scRNA-seq) atlas was established to identify molecular characteristics that might explain prognostic differences observed between patients with HPV⁺ and HPV^– tumours. scRNA-seq and T cell receptor sequencing were carried out in 16 fresh tumour samples from patients with treatment-naive primary PSCC and 6 non-malignant inner prepuce samples. A total of four groups were defined based on HPV and TP53 status: normal (n = 6), HPV⁺ TP53 wild-type (WT; n = 6), HPV^– TP53WT (n = 6) and TP53LOF (irrespective of HPV status; n = 4). Analysis of CSM of patients from an independent international cohort validated the prognostic relevance of these groups, with patients with TP53-mutated tumours having a significantly worse prognosis than patients with TP53WT tumours (P = 0.002). Results from the scRNA-seq analysis showed that TP53LOF tumours had an aggressive phenotype characterized by gene signatures of epithelial-to-mesenchymal transition, angiogenesis and immune exclusion. HPV^– TP53WT tumours showed immune exhaustion, whereas HPV⁺ TP53WT tumours showed a normal epithelial maturation and an upregulation of multiple antibody–drug conjugate targets, suggesting a potential therapeutic utility.

阴茎鳞状细胞癌（PSCC）可分为人乳头状瘤病毒阳性（HPV ⁺ ）和HPV非依赖性（ ^HPV- ）。 HPV ⁺肿瘤的低分化疾病发生率高于 HPV ^–肿瘤。然而，据报道，与^HPV-疾病患者相比，HPV ⁺疾病患者的癌症特异性死亡率 (CSM) 较低。这一证据的部分解释可能是 HPV^疾病患者与 HPV ⁺疾病患者中TP53功能丧失突变 ( TP53 LOF) 的发生率不成比例。

在欧洲泌尿学杂志上发表的一项研究中，建立了 PSCC 单细胞 RNA 测序 (scRNA-seq) 图谱，以确定可能解释 HPV ⁺和 HPV ^–肿瘤患者之间观察到的预后差异的分子特征。对来自未经治疗的原发性 PSCC 患者的 16 个新鲜肿瘤样本和 6 个非恶性包皮内样本进行了 scRNA-seq 和 T 细胞受体测序。根据 HPV 和TP53状态总共定义了四组：正常 ( n = 6)、HPV ⁺ TP53野生型 (WT； n = 6)、HPV ^– TP53 WT ( n = 6) 和TP53 LOF（无论是否HPV 状态； n = 4)。对来自独立国际队列的患者的 CSM 分析验证了这些组的预后相关性， TP53突变肿瘤患者的预后明显比TP53 WT 肿瘤患者差（ P = 0.002）。 scRNA-seq 分析结果显示， TP53 LOF 肿瘤具有侵袭性表型，其特征是上皮间质转化、血管生成和免疫排斥的基因特征。 HPV ^– TP53 WT 肿瘤表现出免疫衰竭，而 HPV ⁺ TP53 WT 肿瘤表现出正常的上皮成熟和多个抗体-药物缀合物靶标的上调，表明潜在的治疗效用。