National trends and survival outcomes of penile squamous cell carcinoma based on human papillomavirus status

Abstract

Background: There are no series evaluating penile squamous cell carcinoma (pSCC) based on human papillomavirus (HPV) infection. Herein, we present national registry data on clinical and survival outcomes for pSCC based on HPV status. Methods:We performed a retrospective review of 1224 pSCC patients with known HPV staining from the National Cancer Database. Patients with cM1 disease, those who did not receive treatment, or had missing follow-up data were excluded. Logistic regression identified factors associated with locally aggressive disease. Univariable, multivariable, and inverse probability of treatment weighting (IPTW)-Cox proportional hazard modeling were used to assess hazard ratios (HR) associated with overall survival (OS).Results: After exclusion criteria, we identified 825 cases of which 321 (38.9%) were HPV positive. The HPV-positivity rate did not significantly change by year. HPV-positive patients were younger, had lower Charlson-Deyo performance score, and resided in areas with both lower median household income and lower school education completion. HPV-positive tumors presented with lower American Joint Committee on Cancer clinical T-stage (cT), poorer differentiation, lower rates of lymphovascular invasion (LVI), but more node-positive disease (cN+). For those who underwent lymph node surgery, there were no differences in final pathologic stage, upstaging, or presence of extranodal extension. Only tumor differentiation, LVI, and performance score were independent predictors for locally aggressive disease. HPV status was not a predictor of OS (IPTW-HR:0.89, p = 0.13). Conclusions:In the largest series evaluating pSCC based on HPV status, HPV-positive tumors were associated with lower cT stages, less LVI, but more cN + disease. More studies on prognostic factors are needed, and time may still be immature to use HPV information for risk stratification.

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features

“…1 However, unlike other anatomic sites with HPV-associated and HPV-independent cancers, in which the former have consistently shown to have a better prognosis than the latter, 7 it is still unclear whether this prognostic implication also applies to PSCC. 8,9 Recently, a few studies have shown a trend towards longer disease-free survival in patients with HPV-associated PSCC. 10,11 Similar to vulvar squamous cell carcinomas, 12 the majority of PSCC develop from premalignant lesions generically named penile intraepithelial neoplasia (PeIN).…”

“…Significant epidemiological differences have been identified between these 2 main types of PSCC, with HPV-associated neoplasms usually arising in men with a history of smoking habit and multiple sexual partners,6 while the HPV-independent tumors are frequently associated with chronic inflammatory conditions, lichen sclerosus, and phimosis 1. However, unlike other anatomic sites with HPV-associated and HPV-independent cancers, in which the former have consistently shown to have a better prognosis than the latter,7 it is still unclear whether this prognostic implication also applies to PSCC 8,9. Recently, a few studies have shown a trend towards longer disease-free survival in patients with HPV-associated PSCC 10,11…”

Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection

“…Nonetheless, data concerning anal SCC is equivocal, and discrepancies might be detected around the world [ 12 , 13 ]. However, the incidence of anal SCC has increased in PLWH over the last few years, although future projections suggest these figures are stabilizing [ 13 , 14 , 15 ]. Conversely, an increase in the incidence of HPV-driven oropharyngeal SCC is predicted in the coming years [ 16 ].…”

“…Conversely, an increase in the incidence of HPV-driven oropharyngeal SCC is predicted in the coming years [ 16 ]. Vulvar, vaginal, and penile SCC are less common than cervical or anal SCC, and disparity data are available for these diseases [ 15 ].…”

Clinical Lymph Node Involvement as a Predictor for Cancer-Specific Survival in Patients with Penile Squamous Cell Cancer

“…Especially in Japan, the age-adjusted incidence of PSCC was reportedly 0.2 per 100,000 men in a population-based study of PC from 15 Japanese selected cancer registries [ 4 ]. The etiology of PSCC is multifactorial with risk factors such as smoking, chronic inflammation, balanitis, history of phimosis, poor hygiene, socioeconomic status, and human papilloma virus (HPV) infection, particularly types 16 and 18 [ 3 , 5 , 6 ]. Lymph node metastasis (LNM) at initial diagnosis is the most important prognostic marker [ 7 , 8 ].…”