Researchers from the Netherlands have reported that vaccination with synthetic long-peptides against human papillomavirus (HPV)-16 was effective in treating vulvar intraepithelial neoplasia (VIN). The details of this study were published in the November 5, 2009 issue of the New England Journal of Medicine.[1]

Vascular intraepithelial neoplasia is a premalignant condition caused by HPV; VIN can lead to vulvar carcinoma. Patients may or may not be symptomatic, and symptoms include itching, burning, and pain. Standard treatments include topical chemotherapy, surgical excision, laser ablation, electrosurgery, and cavitron ultrasonic aspirations. Researchers from the Netherlands have reported that topical Aldara® (imiquimod 5% cream) was effective treatment for HPV-related VIN. HPV-16 is implicated in 75% of VIN cases. The authors of the current study stated that only 1.5% of patients with VIN have spontaneous regression.

The current study evaluated vaccination with synthetic long-peptides against HPV oncoproteins E6 and E7 in 20 patients with grade 3 VIN. Grade 3 VIN is the most severe form of VIN and includes carcinoma in situ of the vulva. The duration of VIN ranged from three to 185 months. There was a mix of unifocal and multifocal VIN in this study group. Patients were vaccinated on three or four occasions.

• At three months after vaccination, 60% of patients had a clinical response with relief of symptoms. Five women had complete regression, and HPV was no longer detected in four.
• At 12 months after vaccination, 79% had a clinical response, and 47% had a complete response.
• At 24 months after vaccination, patients who achieved a complete response maintained this status.
• Responses could be correlated with induction of HPV-specific immunity.
• One patient developed microinvasion, and three developed vulvar carcinoma at six months, 2.5 years, and 3.5 years after vaccination. All women with vulvar carcinoma had had VIN for 10 years or more. Vulvar carcinoma was not observed in patients who achieved a complete response.

Comments: This is a very important study. It demonstrates that vaccination can elicit responses of clinical benefit in women with chronic HPV infections and may prevent vulvar carcinoma from developing. This study may have implications for other persistent viral infections.

Reference:

[1] Kenter GG, Welters MJP, Valentijn ARPM, et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. New England Journal of Medicine. 2009;361:1838-1847.