Tissue specific HPV expression and downregulation of local immune responses in condylomas from HIV seropositive individuals.

Abstract

Objective: To study the eVect of tissue specific human papillomavirus (HPV) expression and its eVect on local immunity in condylomas from HIV positive individuals. Methods: Biopsy specimens of eight penile and eight perianal condylomas from HIV seropositive individuals were analysed. Expression of viral genes (HIV-tat and HPV E7 and L1) was determined by RT-PCR. The status of local immunity also was determined by RT-PCR by measuring CD4, CD8, CD16, CD1a, HLA-DR, and HLA-B7 mRNA levels in the tissues. DiVerentiation was determined by measuring involucrin, keratinocyte transglutaminase, as well as cytokeratins 10, 16, and 17. Proliferation markers such as PCNA and c-myc were also determined. Results: The transcription pattern of HPV in perianal condylomas, which preferentially expressed the early (E7) gene, was diVerent from that of penile condylomas, which primarily expressed the late (L1) gene. This transcription pattern is in good correlation with the keratinisation and diVerentiation patterns of the two epithelia: perianal biopsies preferentially expressed K16 and K17 while penile warts mainly expressed K10, markers of parakeratotic and orthokeratotic epithelia, respectively. Perianal biopsies also showed a higher degree of proliferation (PCNA and c-myc). Interestingly, transcription of HIV-tat was also higher in perianal than in penile biopsies. A high degree of local immunodeficiency was observed in perianal biopsies -that is, levels of CD4, CD16, and CD1a mRNAs were significantly lower. A negative correlation between CD1a (Langerhans cells) levels and HPV E7 levels was established. HPV E7 levels positively correlated with HIV-tat levels. Perianal tissues demonstrated more CD1a depression and tat associated HPV upregulation. Conclusion: HIV influences the expression of HPV genes resulting in local immunosuppression that might lead to an inappropriate immune surveillance of viral infection. Also, tissue type is an important factor in controlling viral transcription in a diVerentiation dependent manner. These findings may explain the higher rate of dysplasia and neoplasia in the perianal area. (Sex Transm Inf 1998;74:349-353)

Effect of imiquimod in anogenital warts from HIV-positive men

“…Previous studies have demonstrated local immunity differences between the penile or anal areas (Arany et al, 1998). However, in our study, we did not find any significant difference in anal versus penile wart clearances.…”

Human Papillomavirus-Associated Oral Warts among Human Immunodeficiency Virus-Seropositive Patients in the Era of Highly Active Antiretroviral Therapy: An Emerging Infection

“…In addition, HPV transcription patterns in HIV-positive subjects differed from those in HIV-negative subjects with condylomata acuminata; transcription of HPV early (E7) genes was predominant in samples obtained from HIV-positive patients, whereas transcription of late (L1) genes was more common in samples obtained from HIV-negative patients [28]. In perianal condyloma tissue samples obtained from HIV-positive patients for biopsy, a negative correlation was seen between E7 gene expression and CD1 (Langerhans cell) mRNA levels [29]. A potential correlate of these findings is that reductions in the HIV RNA level may be associated with reduced E7 gene expression, leading to normalization of CD1 mRNA levels with return of Langerhans cells to the site of HPV infection.…”

Cutaneous malignancy and human immunodeficiency virus disease

“…[147][148][149] HIV-associated immunodysfunction and decreased immune surveillance of HPV-induced dysplasia are likely contributors. However, patients with successful immune reconstitution often do not show improvement of their dysplasia.…”