Sylvie Beaudenon

Bowenoid papulosis of the male and female genitalia: Risk of cervical neoplasia

Sixteen patients with bowenoid papulosis (eleven male patients with bowenoid papulosis of the penis and five female patients with bowenoid papulosis of the vulva) were studied clinically, histologically, and virologically and followed up from 12 months to 5 years. In eleven of sixteen cases of bowenoid papulosis, molecular hybridization disclosed the presence of human papillomavirus type 16. In four cases we found new, not fully characterized human papillomavirus, and in two cases, we found both human papillomavirus 16 and new human papillomavirus (double infection). The mean age of male patients was 33 years and of female patients, 31 years. The mean duration of the disease was 2.4 and 3.6 years, respectively. The lesions cleared or did not recur in eight of eleven male patients after repeated partial excisions and in two of five female patients after conservative surgery. Cervical intraepithelial neoplasia (severe dysplasia) was present in three of five female patients, and human papillomavirus infection of the cervix was present in five of six sexual partners of male patients available for examination. Thus bowenoid papulosis presents a high risk for cervical neoplasia both for female patients and for sexual partners of male patients.

Human papillomaviruses associated with cervical intraepithelial neoplasia. Great diversity and distinct distribution in low- and high-grade lesions.

&NA; All together, 30 genital human papillomavirus (HPV) types have been characterized so far. To evaluate the importance of HPV diversity in associated cervical diseases, we analyzed 188 biopsy specimens obtained from patients with a recent diagnosis of cervical HPV infection or intraepithelial neoplasia (CIN). Of these 188 specimens, 116 were classified as low‐grade CIN (48 cases), high‐grade CIN (53 cases), condylomata acuminata (10 cases), flat condylomas (five cases). Seventy‐two specimens were considered nondiagnostic. Using probes specific for 18 genital HPV types, HPV DNA sequences were detected by Southern blot hybridization in 100 lesions and 21 nondiagnostic specimens. When further analyzed by the polymerase chain reaction, eight HPV‐negative biopsy specimens, four CIN, and four nondiagnostic specimens were positive. Of the 129 positive biopsy specimens, 92 contained at least one of 18 known HPV types and 37 HPV that have not yet been identified. Nine specimens had more than one type. Thirteen HPV types were identified in CIN. The detection rate of HPV 16 increased from 21% in low‐grade CIN to 57% in highgrade CIN. HPV 18 was detected in only 3% of CIN; HPV 31, 33, and 35 were found in 8%. HPV 30, 39, 45, 51, 52, 56, 58, and 61 were detected in 44% of low‐grade CIN but in only 8% of high‐grade CIN. Unidentified HPV were detected in about 25% of low‐grade and high‐grade CIN. Fifty‐seven CIN positive for at least one HPV type were further analyzed by in situ hybridization. Thirty‐five (65%) biopsy specimens were positive, including 21 of 24 low‐grade CIN and 14 of 33 high‐grade CIN. Ten of the 13 previously identified HPV types were detected. Thus, CIN represents an heterogeneous disease from a virologic viewpoint. This fact could explain their variable clinical evolution.

Rearrangements of the upstream regulatory region of human papillomavirus type 6 can be found in both Buschke-Löwenstein tumours and in condylomata acuminata

Clinically malignant Buschke-Löwenstein tumours and benign condylomata acuminata are caused by human papillomaviruses (HPVs), predominantly HPV-6 and -11. In some cases, the HPV-6 genomes found in Buschke-Löwenstein tumours and in verrucous carcinomas differ from HPV-6b isolated from a benign genital wart, by rearrangements of the upstream regulatory region (URR). To evaluate the frequency and role of mutations of the URR of HPV-6 we analysed 42 condylomata acuminata and four Buschke-Löwenstein tumours by the polymerase chain reaction and restriction enzyme cleavage. Using only four different restriction enzymes we could demonstrate four distinct restriction patterns, indicating that naturally occurring HPV-6 isolates display a high degree of DNA polymorphism within the URR. One Buschke-Löwenstein tumour and two condylomata acuminata yielded rearranged URRs with DNA duplications. All three lesions harboured multiple HPV-6 variants, suggesting that cellular or environmental factors facilitate the development of rearrangements. Therefore, rearrangements of the URR may represent only secondary events in condylomata acuminata and Buschke-Löwenstein tumours which do not necessarily confer a higher malignant potential to the infected cell.