Background: The pathogenesis of penile intraepithelial neoplasia (PeIN) is unclear but human papillomavirus (HPV) infection and polymorphisms in human leucocyte antigen (HLA). Objectives: To examine the prevalence of HPV DNA and HLA in PeIN. Methods: Adult Caucasian men with a clinical and histological diagnosis of PeIN, that is, Bowenoid papulosis (BP), Bowen’s disease of penis (BDP) and erythroplasia of Queyrat (EQ) were selected and phenotyped from the clinical records. DNA was extracted from blood and paraffin-embedded sections for HLA and HPV typing, respectively. Human leucocyte antigen allele frequencies were compared with those derived from the UK–based Caucasian population. Results: Seventy-two cases of PeIN (20 BP, 34 BDP and 18 EQ) were studied. Human papillomavirus DNA was identified in 65/72 (90.2%) PeIN; Alphapapillomavirus types were detected in 62/72 (85%) followed by Betapapillomavirus types in 9/72 (12.5%) and cutaneous types in 7/72 (9.7%); HPV16 was the most prevalent genotype at 35/72 (48.6%) followed by HPV33 at 7/72 (9.7%); multiple infections were seen in 18/72 (25%) PeIN. HLA-C*15 (Bonferroni corrected p = 0.049) confers susceptibility to PeIN, whereas HLA-DQA1*01 (corrected p = 0.02) protects against PeIN. HPV16-associated PeIN cases showed no statistically significant association with HLA genotype after multiple corrections. Conclusion: Human papillomavirus is involved in the pathogenesis of PeIN. Immunogenotype may play a role in the pathogenesis of PeIN.
WielandUJurkSWeissenbornS, et al.Erythroplasia of queyrat: coinfection with cutaneous carcinogenic human papillomavirus type 8 and genital papillomaviruses in a carcinoma in situ. J Invest Dermatol2000; 115: 396–401.
2.
KrustrupDJensenHLvan den BruleAJC, et al.Histological characteristics of human papilomavirus-positive and –negative invasive and in situ squamous cell tumour of the penis. Int J Exp Pathol2009; 90: 182–189.
3.
RubinMAKleterBZhouM, et al.Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol2001; 159: 1211–1218.
4.
OlesenTBSandFLRasmussenCL, et al.Prevalence of human papillomavirus DNA and p16INK4a in penile cancer and penile intraepithelial neoplasia: a systemic review and meta-analysis. Lancet Oncol2019; 20: 145–158.
5.
MadkanVKCook-NorrisRHSteadmanMC, et al.The oncogenic potential of human papillomaviruses: a review on the role of genetics and environmental cofactors. Br J Dermatol2007; 157: 228–241.
6.
de KoningMNter ScheggetJEekhofJA, et al.Evaluation of a novel broad-spectrum PCR-multiplex genotyping assay for identification of cutaneous wart-associated human papillomavirus types. J Clin Microbiol2010; 48: 1706–1711.
7.
KleterBvan DoornLJter ScheggetJ, et al.Novel short-fragment PCR assay for highly sensitive broad-spectrum detection of anogenital human papillomaviruses. Am J Pathol1998; 153: 1731–1739.
8.
KleterBvan DoornLJSchrauwenL, et al.Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus. J Clin Microbiol1999; 37: 2508–2517.
9.
de KoningMQuintWStruijkL, et al.Evaluation of a novel highly sensitive, broad-spectrum PCR-reverse hybridization assay for detection and identification of beta-papillomavirus DNA. J Clin Microbiol2006; 44: 1792–1800.
Allele Frequencies in Worldwide Populations. The allele frequency net database, http://www.allelefrequencies.net (accessed 1 April 2012).
12.
ThomsonWBarrettJHDonnR, et al.Juvenile idiopathic arthritis classified by the ILAR criteria: HLA associations in UK patients. Rheumatology (Oxford)2002; 41: 1183–1189.
DohertyDGVaughanRWDonaldsonPT, et al.HLA DQA, DQB, AND DRB genotyping by oligonucleotide analysis: distribution of alleles and haplotypes in British caucasoids. Hum Immunol1992; 34: 53–63.
15.
PorterWMFrancisNHawkinsD, et al.Penile intraepithelial neoplasia: clinical spectrum and treatment of 35 cases. Br J Dermatol2002; 147: 1159–1165.
16.
ChauxAVelazquezEFAminA, et al.Distribution and characterization of subtypes of penile intraepithelial neoplasia and their association with invasive carcinomas: a pathological study of 139 lesions in 121 patients. Hum Pathol2012; 43: 1020–1027.
17.
Renaud-VilmerCCavelier-BalloyBVerolaO, et al.Analysis of alterations adjacent to squamous cell carcinoma of the penis and their relationship with associated carcinoma. J Am Acad Dermatol2010; 62: 284–290.
18.
SantosMLandolfiSOlivellaA, et al.p16 overexpression identifies HPV-positive vulvar squamous cell carcinomas. Am J Surg Pathol2006; 30: 1347–1356.
19.
van SetersMten KateFJvan BeurdenM, et al.In the absence of (early) invasive, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: new insights in histology and aetiology. J Clin Pathol2007; 60: 504–509.
IkenbergHGissmannLGrossG, et al.Human papillomavirus type-16-related DNA in genital Bowen’s disease and in bowenoid papulosis. Int J Cancer1983; 32: 563–565.
22.
SolerCAllibertPChardonnetY, et al.Detection of human pappilomavirus types 6, 11, 16 and 18 in mucosal and cutaneous lesions by the multiplex polymerase chain reaction. J Virol Methods1991; 35(2): 143–157.
23.
Guerin-ReverchonIChardonnetYViacJ, et al.Human papillomavirus infection and filaggrin expression in paraffin-embedded biopsy specimens of extragenital Bowen’s disease and genital Bowenoid papulosis. J Cancer Res Clin Oncol1996; 116(3): 295–300.
24.
MitsuishiTSataTIwasakiT, et al.The detection of human papillomavirus 16 DNA in erythroplasia of Queyrat invading the urethra. Br J Dermatol1998; 138: 188–189.
25.
Ferrándiz-PulidoCMasferrerEde TorresI, et al.Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: correlation with pathologic subtypes, p16INK4a expression, and prognosis. J Am Acad Dermatol2013; 68: 73–82.
SongMJLeeCWKimJH, et al.Association of KIR genes and HLA-Calleles with HPV-related uterine cervical disease in Korean women. Tissue Antigens2013; 81: 164–170.
28.
DavidsonEJDavidsonJASterlingJC, et al.Association between human leukocyte antigen polymorphism and human papillomavirus 16-positive vulva intraepithelial neoplasia in British women. Cancer Res2003; 63: 400–403.
29.
HuYZhangSHHuangYG, et al.Polymorphism of HLA-DRB1 and –DQB1 alleles among young women with cervical squamous cell carcinoma and its relation with human papillomavirus type 16 infection. Zhonghua Yi Xue Za Zhi2010; 90: 2193–2197.
30.
BlackwellJMJamiesonSEBurgnerD. HLA and infectious disease. Clin Microbiol Rev2009; 22: 370–385.
31.
HildesheimAWangSS. Host and viral genetics and risk of cervical cancer: a review. Virus Res2002; 89: 229–240.
