HPV Vaccination after Primary Treatment of HPV-Related Disease across Different Organ Sites: A Multidisciplinary Comprehensive Review and Meta-Analysis.

OBJECTIVE: To assess evidence on the efficacy of adjuvant human papillomavirus (HPV) vaccination in patients treated for HPV-related disease across different susceptible organ sites. METHODS: A systematic review was conducted to identify studies addressing the efficacy of adjuvant HPV vaccination on reducing the risk of recurrence of HPV-related preinvasive diseases. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Sixteen studies were identified for the final analysis. Overall, 21,472 patients with cervical dysplasia were included: 4132 (19.2%) received the peri-operative HPV vaccine, while 17,340 (80.8%) underwent surgical treatment alone. The recurrences of CIN 1+ (OR 0.45, 95% CI 0.27 to 0.73; p = 0.001), CIN 2+ (OR 0.33, 95% CI 0.20 to 0.52; p < 0.0001), and CIN 3 (OR 0.28, 95% CI 0.13 to 0.59; p = 0.0009) were lower in the vaccinated than in unvaccinated group. Similarly, adjuvant vaccination reduced the risk of developing anal intraepithelial neoplasia (p = 0.005) and recurrent respiratory papillomatosis (p = 0.004). No differences in anogenital warts and vulvar intraepithelial neoplasia recurrence rate were observed comparing vaccinated and unvaccinated individuals. CONCLUSIONS: Adjuvant HPV vaccination is associated with a reduced risk of CIN recurrence, although there are limited data regarding its role in other HPV-related diseases. Further research is warranted to shed more light on the role of HPV vaccination as adjuvant therapy after primary treatment.

Therapeutic Efficacy of a Coriolus versicolor-Based Vaginal Gel in Women with Cervical Uterine High-Risk HPV Infection: A Retrospective Observational Study.

INTRODUCTION: A Coriolus versicolor-based vaginal gel is available for treating women with cervical uterine high-risk human papillomavirus (HPV) infection through re-epithelizing and re-balancing microbiota actions. METHODS: A longitudinal retrospective observational study was performed to evaluate efficacy and safety of the gel. Women treated with Coriolus versicolor-based vaginal gel were compared with women not treated with the gel. Both groups were monitored for HPV infection by an HPV DNA test, Pap smear (cytology) and colposcopy at baseline and after 6 months. RESULTS: Overall, 183 high-risk HPV positive women were enrolled (97 treated and 86 controls). After 6 months, the HPV DNA test became negative in 67.0% versus 37.2% of treated and controls, respectively (p < 0.0001). Furthermore, 76.1% versus 40.8% registered a colposcopy improvement (p = 0.0005) and 60.4% versus 40.8% showed a remission (p = 0.05), for treated versus controls, respectively. Regarding to cytology, 78.5% of treated versus 37.7% of controls registered an improvement, while 70.8% of treated versus 34.8% of controls had a remission (p < 0.0001 for both variables). At multivariate analyses adjusted for age, smoking habit, and use of estroprogestinic pill, compared to controls, women treated with the gel showed a significantly higher likelihood to experience the clearence of HPV DNA (OR 4.81; 95% 2.43-9.53), and remission at colposcopy (OR 2.30; 95% 1.00-5.31), and cytology (OR 5.13; 95% 2.40-10.96) at 6 months. No adverse event was reported during the follow-up. CONCLUSIONS: The use of a Coriolus versicolor-based vaginal gel in high-risk HPV patients is safe and effective based on all examined tests.

Efficacy of carboxymethyl beta-glucan in cervical intraepithelial neoplasia: a retrospective, case-control study.

BACKGROUND: Persistent human papillomavirus (HPV) infection constitutes the principal risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. For this reason, new drugs have been studied to support the host immune system against the HPV infection. The aim of this retrospective, case-control study was to detect the efficacy and safety of carboxymethyl ß-glucan (Colpofix®) gel as adjuvant therapy in HPV infection. METHODS: The medical records of patients attending the Colposcopy Service of four hospitals in Rome from 2011 to 2013 were collected. Case arm consisted of patients submitted to local therapy with Colpofix®. Control arm comprised patients who did not receive this therapy. A total of 999 patients were included, divided into four groups, according to their cytological and histological specimens, colposcopy and subsequent management. RESULTS: Local therapy with Colpofix® gel resulted effective with respect to no therapy for the regression of low-grade CIN (CIN1) in patients submitted to follow up (P=0.0204), while it was no effective for the regression of CIN1 submitted to ablative therapy and high-grade CIN (CIN 2+) (P value not significant). CONCLUSIONS: In conclusion, Colpofix® gel represents a valid alternative to "wait and see" strategy in patients affected by CIN1. Further prospective studies are warranted to confirm these results.

HPV-related vulvar diseases and perspectives of p16INK4a immunochemistry: a review of the literature.

INTRODUCTION: Two different types of vulvar intraepithelial neoplasia (VIN), HPV-related and HPV-unrelated, should be considered as two separate entities with different management options. The incidence of HPV-related VIN is increasing worldwide and is implicated in carcinogenesis. Our objective is to investigate the use of p16INK4a immunostaining or p16INK4a/p53 double staining for the detection of HPV-related disease to overcome the problem that histological criteria often have significant overlap. METHODS: A systematic literature search was carried out in the online databases PubMed, EMBASE, Cochrane Library, Clincaltrials.gov and Scopus. The key search terms were HPV, VIN, p16INK4a immunochemistry and p53. RESULTS: We found that nuclear and cytoplasmic immunostaining for p16INK4a was intense and diffuse in HPV-associated lesions and weak and focal in normal vulvar epithelium, nondysplastic lesions, lichen sclerosus and keratinizing vulvar squamous cell carcinoma. p53 nuclear immunostaining was always negative in HPV-related disease. CONCLUSIONS: Our findings indicated that p16INK4a or p16INK4a/p53 immunoreactivity, along with histological diagnosis, could be a convenient means to adequately classify VIN and its connection to HPV infection. Therefore, the clear recognition of HPV-associated VIN would lead to an appropriate strategy of treatment and follow-up.

Management of HPV-related cervical disease: role of p16INK4a immunochemistry. Review of the literature.

This systematic review of 43 studies aims to evaluate the absolute and relative sensitivity and specificity of p16INK4a with regard to uterine cervix lesions, describing innovations and techniques for the detection of high-grade cervical dysplasia and allowing correct treatment. Studies were identified in the PubMed database up to March 2015. The keywords hrHPV, p16INK4a gene, and uterine cervical disease (MeSH terms) were used. Only English-language articles were included. We considered retrospective and prospective studies that assessed p16INK4a or p16INK4a/Ki67 staining, with or without HPV-DNA testing (HC2/PCR) as a comparator test, in cytological/histological specimens for which the diagnosis of ASCUS, LSIL or HSIL was verified with a reference standard. The primary outcome for cervical lesions was evaluation of the absolute p16INK4a immunoreactivity; the secondary outcome was evaluation of the relative p16INK4a immunoreactivity versus HPV testing in those studies where comparator tests were available. p16INK4a was more specific than HPV-DNA test (median values of 56.1% vs. 52.25% in CIN grade ≥2 lesions; 82.5% vs. 53% in negative and CIN grade ≥1 lesions). The main limitation of this study is linked to both qualitative and quantitative p16INK4a levels of expression, while the second limitation is the lack of standardized scales. p16INK4a and HPV-DNA used together increased the sensitivity and negative predictive value for CIN detection. p16INK4a can be considered a biomarker of CIN2 or CIN3, indicating a high risk of relapse or evolution to invasive carcinoma. Also p16INK4a-negative CIN should be considered and further research should be performed.

Endometrial, breast and liver safety of soy isoflavones plus Lactobacillus sporogenes in post-menopausal women.

OBJECTIVE: To assess the safety of a nutraceutical compound containing soy isoflavones and Lactobacillus sporogenes on endometrium, breast and liver function. SETTING: Outpatient Menopausal Clinic. STUDY DESIGN: 130 healthy postmenopausal women suffering from menopausal symptoms were randomized to receive soy isoflavones 60 mg and Lactobacillus sporogenes 1 billion spores (group E: 65 women) or calcium and vitamin D3 (group C: 65 women). Safety of the treatment was assessed at baseline and after 1 year taking into account endometrial thickness, mammographic density, serum levels of transaminases, γ-GT and bilirubin. Efficacy of the treatment was evaluated rating the score of menopausal symptoms at baseline and every 3 months. The statistical analysis was carried out with χ², Fisher exact's test and ANOVA. RESULTS: After 12 months of treatment mammographic density, endometrial thickness and hepatic function did not show significant differences between groups, while menopausal symptoms were progressively and significantly reduced in severity and frequency during treatment with soy isoflavones plus Lactobacillus sporogenes versus calcium plus vitamin D3. CONCLUSION: A 12 months treatment with a nutraceutical compound based on isoflavones and Lactobacillus sporogenes at the recommended doses is safe for endometrium, mammary glands and liver function in postmenopausal women.