Efficacy of a Coriolus versicolor-Based Vaginal Gel in Women With Human Papillomavirus-Dependent Cervical Lesions: The PALOMA Study.

OBJECTIVE: The aim of the study was to evaluate the efficacy of Papilocare, a Coriolus versicolor-based vaginal gel, in repairing human papillomavirus (HPV)-related low-grade cervical lesions. METHODS: The study is a multicenter, open-label, randomized, parallel-group, watchful waiting approach-controlled trial involving 91 HPV-positive women with low-grade Pap smear alterations and consistent colposcopy. RESULTS: The percentage of patients with normal Pap smear and concordant colposcopy 3 and 6 months after receiving treatment (78.0% and 84.9%) was significantly higher than without treatment (54.8% and 64.5%), especially in high-risk HPV patients (79.5% and 87.8% vs 52.0% and 56.0%). At 6-month visit, overall HPV clearance was achieved by a greater number of patients receiving treatment (59.6%) compared with those without treatment (41.9%), especially high-risk HPV ones (62.5% vs 40.0%). The cervical re-epithelization score was significantly higher with treatment (mean = 4.5) than without (mean = 4.1). Compared with baseline, perceived stress decreased in the treatment group (from 21.1 to 19.0) and increased in the control group (from 17.7 to 20.7). A total of 7 possible or probable treatment-related adverse events were reported, most of them (n = 6) being mild or moderate in severity. CONCLUSIONS: Treatment with Papilocare has demonstrated a better clinical benefit than the conventional watchful waiting approach in clinical practice for total and high-risk HPV patients in terms of its efficacy to treat HPV-related cervical lesions and to clear all HPV strains after a single 6-month period. It has demonstrated an adequate safety and tolerability and confers additional benefits such as higher re-epithelization, stress reduction, and high treatment adherence.

Radical Hysterectomy: Efficacy and Safety in the Dawn of Minimally Invasive Techniques.

STUDY OBJECTIVE: To analyze the effect that the introduction of minimally invasive procedures has had on surgical and oncologic outcomes when compared with conventional open radical hysterectomy (ORH) in a national reference cancer after 17 years of experience in radical hysterectomy. DESIGN: A prospective controlled study (Canadian Task Force classification II-2). SETTING: A university teaching hospital. PATIENTS: All patients who underwent radical hysterectomy as primary treatment for cervical cancer in our institution between May 1999 and June 2016, with a total of 188 patients. INTERVENTIONS: Patients underwent ORH or minimally invasive surgery (MIS) (i.e., laparoscopic or robotically assisted radical hysterectomy). MEASUREMENTS AND MAIN RESULTS: Seventy-six patients underwent ORH, 90 laparoscopic radical hysterectomy, and 22 robotically assisted radical hysterectomy. Blood loss and hospital stay were inferior in the MIS group (p <.0001). The laparotomic group presented shorter operation times (p = .0001). With a median follow-up of 112.4 months, a total of 156 patients (83%) were alive and free of disease at the time of the data analysis. Overall survival was higher in the MIS group when compared with the ORH group (91 vs 78.9, p = .026). There were no differences regarding recurrence rates between the surgical approaches. CONCLUSION: With 1 of the largest follow-up periods in the literature, this study provides added evidence that MIS could become the preferable surgical approach for early-stage cervical cancer since it appears to reduce morbidity without affecting oncologic results.

Vaginal Intraepithelial Neoplasia: Clinical Presentation, Management, and Outcomes in Relation to HIV Infection Status.

OBJECTIVES: The data available on vaginal intraepithelial neoplasia (VAIN) and infection by HIV are scarce. We therefore aimed to review the clinical presentation, management, and survival outcomes of VAIN in this group of women. MATERIALS AND METHODS: This is an observational cohort study of women diagnosed with VAIN for a 23-year period. Clinical characteristics and outcomes were analyzed according to women's HIV infection status. Disease-free and progression-free survival were compared between groups. RESULTS: Twenty-two of 87 women were HIV positive (25.3%) compared with the HIV-negative group, HIV-positive women were younger (median age = 39 vs 57 years, p < .001) and more frequently smokers (p < .001). They also presented with multifocal and multicentric disease more often (p = .004 and p = .033, respectively) in relation to infection by human papillomavirus. All HIV-positive women were receiving antiretroviral treatment. The median time from the diagnosis of HIV to the development of VAIN was 14 years (range = 1-22 years). There were no significant differences in survival outcomes between groups. CONCLUSIONS: HIV-positive women are at an increased risk of developing VAIN and frequently present at a younger age with multifocal and multicentric disease. Vaginal intraepithelial neoplasia lesions can develop many years after the initial diagnosis of HIV infection reason why prolonged surveillance is essential to enable prompt diagnosis and treatment.

Risk factors for progression or persistence of squamous intraepithelial lesions diagnosed during pregnancy.

OBJECTIVE: This study aimed to assess the risk of progression/persistence of squamous intraepithelial lesions (SILs) during pregnancy according to the age of the woman, the grade of the lesion, the type of human papillomavirus (HPV) infection, and the mode of delivery. MATERIALS AND METHODS: Eighty pregnant women with abnormal cytologic result at the first antenatal visit were evaluated. Postpartum cytologic and histologic findings were compared with the antepartum findings. RESULTS: There were 40 patients with low-grade SIL and 40 with high-grade SIL (HSIL). The overall regression rate was 32.5%. There were 19 patients 25 years or younger and 61 patients older than 25 years. The regression rate among younger patients was 52.6% versus 26.2% among those older than 25 years (relative risk [RR] = 2.01, 95% confidence interval [CI] = 1.10-3.66). The regression rate was 45% in the group of low-grade SIL and 20% in the group of HSIL (RR = 2.25, 95% CI = 1.11-4.57). In patients with HSIL, those older than 25 years had a 2-fold increased risk of progression/persistence than younger patients. High-risk HPV-positive samples were typed in 44 cases, 21 of which (47.7%) were positive for HPV-16. The regression rate was 9.5% for HPV-16-positive cases and 52.2% for HPV-16-negative cases (RR = 5.48, 95% CI = 1.39-21.68). The risk of progression or persistence of the lesion according to mode of delivery did not show significant differences (RR = 1.15, 95% CI = 0.82-1.63). CONCLUSIONS: Age of the patient older than 25 years, HSILs, and HPV type 16 infection are risk factors for the progression or persistence of intraepithelial lesions of the cervix in the postpartum period.

Efficacy of a Coriolusversicolor-Based Vaginal Gel in Human Papillomavirus-Positive Women Older Than 40 Years: A Sub-Analysis of PALOMA Study.

In the PALOMA trial, Papilocare® demonstrated efficacy in repairing low-grade cervical lesions related to human papillomavirus (HPV). This sub-analysis aimed to evaluate its efficacy in repairing these cervical lesions and clearing HPV in women aged older than 40 years. This was a multicenter, randomized, open-label, parallel-group, controlled clinical trial. Patients with low-degree HPV-dependent cervical lesions receiving 6-month treatment with the vaginal gel were compared to those with a watchful waiting approach. Among the 41 women analyzed (aged 47.7 years), 31 presented high-risk (HR) oncogenic HPV subtypes, and 14 had 16-18-31 HPV genotypes. After 6 months, normalized cytology and concordant colposcopy were achieved by a greater percentage of treated women. The difference was significant in the total population (92.3% vs. 50.0%, p = 0.007), and HR-HPV subpopulation (90.5% vs. 33.3%, p = 0.003). In the HR HPVs-16-18-31 subpopulation, the values were 75.0% and 40.0% (p = 0.293). In the total population, 61.5% of treated patients obtained HPV clearance, compared to 50.0% in the control group. Regarding the HR-HPV subpopulation, these values were 66.7% and 44.4%, respectively. Papilocare® demonstrated significant efficacy in repairing low-degree HPV-related cervical lesions and a positive trend to clear HPV in women older than 40 years old in comparison to the watchful waiting approach.

Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa.

HIV viral reservoirs are established very early during infection. Resident memory T cells (TRM) are present in tissues such as the lower female genital tract, but the contribution of this subset of cells to the pathogenesis and persistence of HIV remains unclear. Here, we show that cervical CD4+TRM display a unique repertoire of clusters of differentiation, with enrichment of several molecules associated with HIV infection susceptibility, longevity and self-renewing capacities. These protein profiles are enriched in a fraction of CD4+TRM expressing CD32. Cervical explant models show that CD4+TRM preferentially support HIV infection and harbor more viral DNA and protein than non-TRM. Importantly, cervical tissue from ART-suppressed HIV+ women contain high levels of viral DNA and RNA, being the TRM fraction the principal contributor. These results recognize the lower female genital tract as an HIV sanctuary and identify CD4+TRM as primary targets of HIV infection and viral persistence. Thus, strategies towards an HIV cure will need to consider TRM phenotypes, which are widely distributed in tissues.

Vulvar intraepithelial neoplasia: clinical presentation, management and outcomes in women infected with HIV.

OBJECTIVE: Immunocompromised patients are at increased risk of developing preinvasive lesions of the lower genital tract. There are a limited number of studies on vulvar intraepithelial neoplasia (VIN) in HIV-positive women. We aimed to review the clinical presentation of VIN, management and survival outcomes in this group of patients. DESIGN: Observational cohort study. METHODS: Data was collected from women diagnosed with VIN at the Hospital Vall d'Hebron between September 1994 and October 2011. The main outcome measures were recurrence-free survival (RFS) and progression-free survival (PFS). Risk factors for recurrence and progression were assessed using univariate and multivariate analyses. RESULTS: Thirty-seven out of 107 women were HIV positive (34.6%). The median follow-up time was 32 (range 12-179) months. Compared with the HIV-negative group, HIV-positive women were younger (median age 37 vs. 44 years, P = 0.003) and presented with multifocal and multicentric disease more frequently (63.6 vs. 22.2% and 84.8 vs. 43.3%, respectively, P < 0.0001). RFS and PFS were lower in the HIV-positive group (42.4 vs. 71.4% P = 0.043 and 69.7 vs. 95.2% P = 0.006, respectively). RFS was significantly associated to multicentric and multifocal disease on multivariate analysis. PFS was associated to HIV infection on univariate analysis. CONCLUSION: HIV-positive women are at increased risk of developing VIN and frequently present at a younger age with multifocal and multicentric disease. They have shorter RFS and PFS compared with HIV-negative women. Close surveillance of the lower genital tract is mandatory to enable early recognition and treatment of any suspicious lesions. Close follow-up after treatment of VIN is essential to exclude early recurrence or progression.