Abstract：
OBJECTIVE: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV-positivity, and evaluate the prognostic impact of relevant clinicopathologic variables.
METHODS: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression.
RESULTS: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P = 0.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1).
CONCLUSIONS: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value.
METHODS: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression.
RESULTS: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P = 0.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1).
CONCLUSIONS: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value.
摘要：
目的：关于阴茎鳞状细胞癌（pSCC）患者的北美队列数据很少。在这里，我们旨在评估各种方法的敏感性，以确定人乳头瘤病毒（HPV）状态，确定高危型HPV阳性的患病率，并评估相关临床病理变量对预后的影响。
方法：纳入pSCC患者（n=121）在单一机构连续接受部分/全部阴茎切除术（2000-2022）治疗。HPV状态（基于免疫组织化学[IHC]，原位杂交[ISH]，和泛病毒宏基因组测序[PMS])，组织学特征，并对结果进行了审查。结果事件包括由于疾病和进展导致的死亡。
结果：大多数患者为白人（105/121，86.8％）。37例（30.6%）高危型HPV阳性，形态学评估的灵敏度为97.3%(95%置信区间[CI]，86.2-99.5）用于预测与IHC/ISH/PMS相比的高危HPV状态。与高危HPV阳性患者相比，高危HPV阴性患者的疾病进展更为常见（HR2.74，CI1.12-8.23，P=0.03）。此外，在高危型HPV阴性患者中，患有中度-低分化肿瘤的患者的疾病特异性死亡率增加（32.6％，CI17.1-48.1）与高分化肿瘤（0%）相比。在高危HPV阳性患者中，具有基底细胞形态的患者具有较低的疾病特异性死亡率(0%vs14.4%，CI0.0-33.1）。
结论：我们在约三分之一的pSCC患者中证实了高危型HPV阳性。仅形态学评估在正确确定HPV状态方面具有很高的敏感性。我们的结果表明，高危HPV状态和形态学特征（高危HPV阴性，高危型HPV阳性pSCC中的基底细胞亚型）可能具有预后价值。
方法：纳入pSCC患者（n=121）在单一机构连续接受部分/全部阴茎切除术（2000-2022）治疗。HPV状态（基于免疫组织化学[IHC]，原位杂交[ISH]，和泛病毒宏基因组测序[PMS])，组织学特征，并对结果进行了审查。结果事件包括由于疾病和进展导致的死亡。
结果：大多数患者为白人（105/121，86.8％）。37例（30.6%）高危型HPV阳性，形态学评估的灵敏度为97.3%(95%置信区间[CI]，86.2-99.5）用于预测与IHC/ISH/PMS相比的高危HPV状态。与高危HPV阳性患者相比，高危HPV阴性患者的疾病进展更为常见（HR2.74，CI1.12-8.23，P=0.03）。此外，在高危型HPV阴性患者中，患有中度-低分化肿瘤的患者的疾病特异性死亡率增加（32.6％，CI17.1-48.1）与高分化肿瘤（0%）相比。在高危HPV阳性患者中，具有基底细胞形态的患者具有较低的疾病特异性死亡率(0%vs14.4%，CI0.0-33.1）。
结论：我们在约三分之一的pSCC患者中证实了高危型HPV阳性。仅形态学评估在正确确定HPV状态方面具有很高的敏感性。我们的结果表明，高危HPV状态和形态学特征（高危HPV阴性，高危型HPV阳性pSCC中的基底细胞亚型）可能具有预后价值。
