Immunogenetics and human papillomavirus (HPV) in male genital lichen sclerosus (MGLSc)

Abstract

Background The pathogenesis of male genital lichen sclerosus (MGLSc) is controversial. Incriminated factors include infection with human papillomavirus (HPV) and autoimmunity (e.g. Human Leukocyte Antigen [HLA]). To address the roles of HLA and HPV in MGLSc we studied adult Caucasian males with a clinical and histological diagnosis of MGLSc. The men in the study attended two specialised Male Genital Dermatoses Clinics between July 2011 and September 2012 and were selected and phenotyped from the clinical records. DNA was extracted from blood and paraffin-embedded biopsy sections, for HLA and HPV typing, respectively. HLA allele frequencies were compared with those derived from the UK-based Caucasian population. Eighty-eight cases of MGLSc were identified. HPV DNA was detected in 33/88 (37.5%) cases of MGLSc. HPV16 was the most prevalent type found: 11/88 (12.5%) MGLSc. No statistically significant HLA associations were established but HLA-B*35, -B*51, -C*15, -DRB1*04, -DRB1*10 (predisposition) and -DQA1*01 (protection) were revealed as alleles of interest. HPV16-associated MGLSc cases showed no statistically significant association with HLA genotype. The relationship between HPV and MGLSc suggests a passenger effect rather than a pathogenic role. HLA is not associated with MGLSc nor co-existent HPV16.

Alpha, Beta, and Gamma Human Papillomaviruses in Genital Lichen Sclerosus: A Retrospective Cross-Sectional Study

“…Regarding the HPV types, we observed a lower variability if compared with others, which observed up to 18 different HPVs in LS lesions. 23 However, the predominance of HPV16 is in accordance with what was observed by Hald et al 8 in 155 male and female LS cases, in which HPV16 contributed to 64% of all HPV genotypes detected.…”

“…Similar to what was found in women, alpha HPV prevalence in penile lesions (10.2%) is not far from the pooled estimate for male genital infection of a meta-analysis on men in Europe (12.4%) 30 . Supporting this observation, many studies demonstrated no significant association of alpha HPV infection with male LS 23,31 . Although Nasca et al 22 showed that HPV infection rate was higher among male LS patients than healthy controls, the difference was not statistically significant.…”

“…30 Supporting this observation, many studies demonstrated no significant association of alpha HPV infection with male LS. 23,31 Although Nasca et al 22 showed that HPV infection rate was higher among male LS patients than healthy controls, the difference was not statistically significant.…”

Lichen sclerosus: The 2023 update

“…In a case series of 329 patients, no correlation between MGLS and HPV infection was shown ( 61 ). Furthermore, in HPV16-associated MGLS cases, the role of the virus may be rather accidental than pathogenic, as also non-specific HPV-associated gene expression patterns have been found ( 80 , 81 ).…”

Reply to: ‘Does routine histology alter management post-circumcision?’

“…Not ‘studies’ actually, but it is manifestly good clinical practice borne out by evidence published by us, e.g. (a) in an account of 329 cases of lichen sclerosus, 177 (53.8%) had biopsies or circumcisions and in 120 there was corroborative histology from biopsy ( n =49) or circumcision ( n =71) specimens; five (2.8%) had lichen sclerosus in conjunction with PeIN); 57 (17.3% of the total cohort; 32.2% of the number biopsied) showed non-specific balanoposthitis; of those men with histopathological evidence of lichen sclerosus, six (5%) had histopathological evidence of concurrent human papillomavirus (HPV) infection, 6 (b) from another series of 301 cases, in 260 patients with isolated lichen sclerosus, clinical diagnosis was achieved in ~95% of cases; in 41 patients with lichen sclerosus and PeIN combined, ~85% were diagnosed histologically on biopsy and the remaining ~15% confirmed retrospectively following histology after circumcision; in those patients with isolated male genital lichen sclerosus (MGLSc) who were diagnosed clinically, 93 had histological results available from subsequent circumcision; histology confirmed the diagnosis in 87 patients (93.5%), but did not show evidence of MGLSc in six (6.5%) where the findings were non-specific, 5 (c) in 88 cases three (3.4%) reported no apparent history of genital warts but koilocytosis was seen in the penile biopsies; however 33/88 (37.5%) showed the presence of HPV DNA (although HPV is not thought to be directly pathogenic in lichen sclerosus), 7 and (d) as stated in our fifth paragraph above, in some patients where lichen sclerosus alone was suspected, biopsy or circumcision showed PeIN; 2 it is not uncommon in our practice to be ‘surprised’ by a histological diagnosis of invasive squamous carcinoma in patients circumcised for clinically evident lichen sclerosus. We do not apologise for the detail recounted above; these findings clearly demonstrate that the differential diagnosis of male genital dermatoses can be a complicated endeavour and that clinical impressions cannot be relied upon.…”