Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure of therapeutic vaccination.

BACKGROUND: Cellular immunity is involved in spontaneous clearance of anogenital warts caused, most typically, by human papillomavirus (HPV) type 6 or 11, supporting the concept of therapeutic vaccination. A therapeutic vaccine composed of HPV-6 L2E7 fusion protein and AS02A adjuvant was evaluated in conjunction with conventional therapies in subjects with anogenital warts. METHODS: A total of 457 subjects with anogenital warts were screened, of which 320 with HPV-6 and/or HPV-11 infection were enrolled into 2 double-blind, placebo-controlled substudies. Three doses of vaccine or placebo were administered along with either ablative therapy or podophyllotoxin. RESULTS: Although a positive trend toward clearance was seen in patients infected with only HPV-6, in neither substudy did the vaccine significantly increase the efficacy of conventional therapies, despite induction of adequate immune responses. Extensive HPV typing by polymerase chain reaction demonstrated that a majority of screened subjects (73.7%) were infected with HPV-6 and/or HPV-11 and that a large proportion (40.1%) were infected with multiple HPV types. HPV types that put subjects at high risk of development of cervical cancer were detected in 39.8% of subjects. CONCLUSIONS: Infection with multiple HPV types, including high-risk types, is common in anogenital wart disease. Therapeutic vaccination failed to increase the efficacy of conventional therapies.

Cytologic detection of human papillomavirus DNA in normal male urethral samples.

OBJECTIVES: To quantify the existence of human papillomavirus (HPV) infection without detectable lesions in the male urethra, and to verify the sensitivity and specificity of ureteral cytology. We compared the results of clinical and colposcopic examinations, ureteral cytology, and HPV DNA testing by polymerase chain reaction amplification in the male partners of women with genital HPV disease. METHODS: A total of 110 cytobrush samples of urethral cells from male sexual partners of women with genital HPV-associated lesions were analyzed by cytology and for virologic detection of HPV 6/11, 42, 16/18 by polymerase chain reaction followed by Southern blot hybridization. The results were correlated with the presence or absence of genital HPV-associated lesions. RESULTS: HPV DNA was detected in 1 sample (3%) from men without visible lesions, in 5 samples (15%) from men with penile lesions but without urethral lesions, and in 16 men with urethral lesions (78%). Cytology showed cellular changes suggesting HPV infection in 81% of men with urethral lesions, but also in 15% of men without lesions. CONCLUSIONS: Our results show that HPV-DNA positivity in the absence of clinically or colposcopically detected lesions is a rare event. Although sensitive enough, cytology is not specific, and its use as a screening tool may lead to a high number of false-positive results.

Frequency of herpes simplex virus, cytomegalovirus and human papillomavirus DNA in semen.

Herpes simplex virus (HSV-2) and cytomegalovirus (CMV) infections produce brain damage in the newborn, and human papillomavirus (HPV) plays a role in cervical carcinogenesis. To assess the frequency of herpes virus and HPV in semen and its role in transmission, semen from 111 male partners of women with histologically-detected genital HPV infection was analysed for HSV, CMV and HPV infection. We used cell culture to detect HSV and CMV, and polymerase chain reaction (PCR) for HPV. Virological findings in the sperm were correlated to the presence or absence of HPV-associated genital lesions and to the viral type. Viral cultures yielded HSV-2 DNA in 9% and CMV DNA in 6.3% of cases. No correlation was established with a history of clinically apparent infection for HSV. HPV-DNA was detected in 23.4% of semen by PCR techniques: in 48% of subjects with urethral lesions, in 22% of patients with penile lesions, in 2% of patients without HPV-associated lesions. HPV-DNA type 16 was detected in 3.6% of cases. Patients with a positive HPV semen sample and penile or urethral lesions had the same HPV type detected in the two specimens. The study shows a high detection of clinically inapparent HSV and CMV, but does not confirm high HPV prevalence in semen from men without detectable lesions. Our study also suggests that the mechanism for semen contamination by HPV is the exfoliation of infected cells from urethral lesions during semen ejaculation, and probably, by abrasion from penile lesions. This could result in the contamination of semen used in assisted reproductive technology.