Heideman Daniëlle A M, Waterboer Tim, Pawlita Michael, Delis-van Diemen Pien, Nindl Ingo, Leijte Joost A, Bonfrer Johannes M G, Horenblas Simon, Meijer Chris J L M, Snijders Peter J F
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
J Clin Oncol. 2007 Oct 10;25(29):4550-6. doi: 10.1200/JCO.2007.12.3182.
Human papillomavirus (HPV) infections are suggested to be involved in the development of penile squamous cell carcinoma (SCC), but comprehensive studies to define the association are limited. Therefore, we performed molecular and serologic analyses for a broad spectrum of HPV types on a large series of 83 penile SCCs, and we compared serological findings to those of age-matched male controls (N = 83).
Penile SCCs were subjected to detection and typing assays for mucosal and cutaneous HPVs and to subsequent, type-specific viral load and viral gene expression assays. Sera of patients and of controls were analyzed for type-specific mucosal and cutaneous HPV L1, E6, and/or E7 antibodies using bead-based, multiplex serology.
HPV DNA of mucosal and/or cutaneous types was found in 46 of 83 (55%) penile SCCs. HPV16 was the predominant type, appearing in 24 (52%) of 46 of penile SCCs. The majority of HPV16 DNA-positive SCCs (18 of 24; 75%) demonstrated E6 transcriptional activity and a high viral load. Additionally, HPV16 molecular findings were strongly associated with HPV16 L1-, E6-, and E7-antibody seropositivity. Furthermore, serologic case-control analyses demonstrated that, in addition to the association of HPV16 with penile SCC, seropositivity against any HPV type was significantly more common in patients compared with in controls. HPV18 and HPV6 seropositivity were associated with HPV16-negative SCCs but were not correlated to molecular findings.
HPV16 is the main HPV type etiologically involved in the development of penile SCC. Although individuals who develop penile SCC show a greater prior exposure to a broad spectrum of HPV types, insufficient evidence was found to claim a role for HPV types other than HPV16 in penile carcinogenesis.
人乳头瘤病毒(HPV)感染被认为与阴茎鳞状细胞癌(SCC)的发生有关,但确定这种关联的全面研究有限。因此,我们对83例阴茎SCC进行了一系列广泛的HPV类型的分子和血清学分析,并将血清学结果与年龄匹配的男性对照组(N = 83)进行了比较。
对阴茎SCC进行黏膜和皮肤HPV的检测和分型测定,随后进行型特异性病毒载量和病毒基因表达测定。使用基于微珠的多重血清学分析患者和对照组血清中的型特异性黏膜和皮肤HPV L1、E6和/或E7抗体。
83例阴茎SCC中有46例(55%)检测到黏膜和/或皮肤型HPV DNA。HPV16是主要类型,在46例阴茎SCC中的24例(52%)中出现。大多数HPV16 DNA阳性的SCC(24例中的18例;75%)表现出E6转录活性和高病毒载量。此外,HPV16分子检测结果与HPV16 L1、E6和E7抗体血清阳性密切相关。此外,血清学病例对照分析表明,除了HPV16与阴茎SCC的关联外,患者中任何HPV类型的血清阳性率均显著高于对照组。HPV18和HPV6血清阳性与HPV16阴性的SCC相关,但与分子检测结果无关。
HPV16是阴茎SCC发生的主要病因型HPV。虽然发生阴茎SCC的个体先前对多种HPV类型的暴露更多,但没有足够的证据表明除HPV16外的其他HPV类型在阴茎致癌过程中起作用。