Clinical and immunological response to photodynamic therapy in the treatment of vulval intraepithelial neoplasia.

Vulval intraepithelial neoplasia (VIN) is a premalignant condition of the vulva and its incidence is increasing. The common type of VIN is associated with oncogenic types of human papilloma virus (HPV) infection. The standard modalities of treatment for VIN, surgical excision and laser ablation, are both sub-optimal, associated with high rates of disease recurrence. There is a need for non-surgical treatment options for VIN and photodynamic therapy (PDT), by altering the local immunological parameters, has the potential to clear both VIN and HPV. This article reviews the studies of PDT treatment for VIN and discusses the clinical and immunological responses to PDT treatment in the various studies.

Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia.

BACKGROUND: Vulval intraepithelial neoplasia (VIN) is a premalignant condition, which is frequently associated with type HPV16 infection, and multifocal disease has high rates of surgical treatment failure. METHODS: We report a phase II clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. Histology and HPV testing of biopsies were performed at weeks 0, 10, 20 and 52. Intralesional infiltration of T-cell subsets and lymphocyte proliferation for HPV systemic immune responses were also assessed. RESULTS: Lesion response (complete regression of VIN on histology) was observed in 32% (6 out of 19) of women at week 10, increasing to 58% (11 out of 19) at week 20 and 63% (12 out of 19) at week 52. At this time, 36% (5 out of 14) of lesions showed HPV16 clearance and 79% (15 out of 19) of women were symptom free. At week 20, after treatment with imiquimod and vaccination, there was significantly increased local infiltration of CD8 and CD4 T cells in lesion responders; in contrast, non-responders (persistent VIN by histology) showed an increased density of T regulatory cells. After vaccination, only lesion responders had significantly increased lympho-proliferation to the HPV vaccine antigens. CONCLUSION: The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically.

A randomised controlled trial comparing two different local anaesthetic injection techniques prior to LLETZ.

The aim of this study was to compare two different anaesthetic injection techniques and assess whether one was less painful than the other when used prior to LLETZ. A total of 60 women undergoing LLETZ were randomised into two groups. The control group received local anaesthesia by deep injection into the substance of the cervix. The study group received an equivalent amount of local anaesthetic but this was injected superficially prior to deep injection into the cervix. Pain was assessed using a visual analogue scale. Women in the study arm experienced less pain than controls during injection of local anaesthetic.

The IL-10 -1082G polymorphism is associated with clearance of HPV infection.

The role of cytokines in protecting against human papillomavirus (HPV) and HPV-associated disease is not fully understood. We compared the frequency of the interleukin (IL)-10 polymorphism (G allele) at position --1082 and the distribution of GG/GA/AA genotypes among 116 HPV-positive women, grouped according to their cervical cytological profiles, with 119 HPV-negative controls with normal smears. No difference was observed in genotype frequency between the groups. Among women in the HPV-positive, smear-normal group, who were re-tested for HPV after 12 months, there was a significant inverse association between presence of at least one variant G allele (high activity) and HPV persistence (OR per G allele = 0.082 [95% CI 0.009-0.73], P= 0.001; after controlling for ethnicity). This association remained significant after controlling for age, smoking and hormonal contraception (OR = 0.028 [95% CI 0.001-0.66], P= 0.001). This preliminary study suggests that higher levels of IL-10 may prevent cervical neoplasia through their role in eliminating HPV.