Table 1 Included studies
Author | Study Design | Participants | N | Average Disease Duration | Intervention | Follow up | Results |
|---|---|---|---|---|---|---|---|
Baldwin 2003 [20] | Case series | Aged 42–54 (mean age 46) HG HPV positive VIN/VAIN | 12 | 3–14 months | TA-HPV, a live recombinant vaccinia virus, expressing modified versions of the E6 and E7 open reading frames from HPV-16 and HPV-18. | 6 months | Enhanced vaccine T-cell specific response (60%) Symptom relief (25%) Lesion response (reduction in size; 83%) Regression to normal histology (8%) HPV negative post intervention (8%) No disease progression over the 6 months follow up period |
Daayana 2010 [21] | Case series | Aged 18–70 (mean 46) Biopsy proven VIN2/3 | 20 | 7 years | Weeks 1–8 Imiquimod then three intramuscular doses of TA-CIN - E6 and E7 L2 fusion protein - (1 ml of 128 mg/ml) at weeks 10, 14 and 18. | 1 year | Lymphoproliferative response (84%) Symptom relief (68.4%) Lesion response (79%) Regression on Histology (63%) HPV negative (74.3%) 1 progression to invasive cancer after the trial period |
Davidson 2003 [22] | Case series | HPV16 positive HG VIN | 18 | 6.4 years (6 months – 17 years) | Vaccination with TA-HPV E6/E7 (2.5 × 105 plaque-forming units) by a single dermal scarification to the deltoid region of the upper arm. | 6 months | Immune response (94%) Symptom relief (50%) Lesion response (44%) Regression on histology (5.5%) HPV negative (11%) |
Fiander 2006 [23] | Case series | Aged 18–65 (median 40) Biopsy proven HG non-cervical ano-genital intraepithelial neoplasia | 29 | 2–120 months | Three prime vaccinations of TA-CIN (533 μg) were given intramuscularly into the deltoid region days 0, 28, and 56 followed by TA-HPV administered by dermal scarification of the deltoid (2.5 × 105 plaque-forming units) on day 72. | 6 months | Symptom relief (56%) Lesion response - CR (disappearance of lesion) seen in 1/29 (3%), partial (> 50%) in 5 (17%), stable disease in 18 (62%), progression in 5 patients (17%) Regression on histology (17%) HPV negative (14%) Nil developed invasive lesions Trend for older women to respond Prime boost strategy does not demonstrate additional efficacy compared to the recombinant vaccine (TA-HPV) alone |
Kenter 2009 [19] | Case series | Aged 23–61 (mean 29) Histologically confirmed HPV16 positive VIN3 | 22 | 3–185 months | Vaccine containing nine HPV-16 E6 and four HPV-16 E7 synthetic peptides, the vaccine was administered subcutaneously at 3-week intervals | 1 year | Immune response − 85% had circulating T cells post vaccine Symptom relief (63%) Lesion response (79%) Regression on histology (45%) HPV status – 4/20 (20%) negative at 3 months |
Muderspach 2000 [24] | Case series | Median age 29 CIN2/3 or VIN 2/3 | 16 | – | Vaccination HPV-16 E7 12–20 peptide, 3 groups varied dose LEEP as standard in CIN patients | 1 month | Immune response 10/16 (63%) Lesion response 9/17 (53%) HPV status 12/18 negative (67%) Symptom relief and histology not reported |
Samuels 2017 [25] | Case series | Median age 50 Biopsy proven HPV16 positive uVIN | 12 | – | TTFC-E7SH, E. coli derived plasmid backbone, fusion protein of tetanus toxin, and shuffled version of HPV16 E7 oncoprotein. Patients vaccinated with a fixed dose on days 0,3, and 6 then received booster at week 4. Administration using novel intradermal application (tattooing). Cohort 1–0.2 mg injection, cohort 2 – 2 mg. | 3 months | Symptoms – no response after 3 months Lesions – no response after 3 months Histological features – no response after 3 months Vaccine induced T cell responses found in 4/12 patients |