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Background: The optimal management of vulvar high-grade squamous intraepithelial lesions (vHSILs) is challenging. Surgery is the standard treatment, but recurrences are observed in half of patients. Medical treatment with imiquimod is an effective alternative, but the two modalities have not been compared in a randomised trial. The aim of this study was to compare the clinical effectiveness, histological response, human papillomavirus (HPV) clearance, acceptance, and psychosexual morbidity of primary imiquimod treatment versus surgical treatment in women with vHSIL., Methods: This study was a multicentre, randomised, phase 3, non-inferiority clinical trial done by the Austrian Gynaecological Oncology group at six hospitals in Austria. We recruited female patients aged 18-90 years with histologically confirmed vHSIL with visible unifocal or multifocal lesions. Main exclusion criteria were clinical suspicion of invasion, a history of vulvar cancer or severe inflammatory dermatosis of the vulva, and any active treatment for vHSIL within the previous 3 months. Women with known immunodeficiency, who were pregnant, or who were lactating were excluded. Patients were randomly assigned (1:1) by block randomisation to imiquimod or surgery, and stratified by unifocal or multifocal disease. Treatment with imiquimod was self-administered in a slowly escalating dosage scheme up to three times per week for a period of 4-6 months. Surgery consisted of excision or ablation. Patients were assessed with vulvoscopy, vulvar biopsy, HPV tests, and patient-reported outcomes at baseline and after 6 months and 12 months. The primary endpoint was complete clinical response (CCR) at 6 months after local imiquimod treatment or one surgical intervention. Primary analysis was per protocol with a non-inferiority margin of 20%. This trial is registered at ClinicalTrials.gov, NCT01861535., Findings: 110 patients with vHSIL (78% with unifocal vHSIL and 22% with multifocal vHSIL) were randomly assigned between June 7, 2013, and Jan 8, 2020. Clinical response to treatment could be assessed in 107 patients (54 in the imiquimod group and 53 in the surgery group), and 98 patients (46 in the imiquimod group and 52 in the surgery group) completed the study per protocol. 37 (80%) of 46 patients using imiquimod had CCR, compared with 41 (79%) of 52 patients after one surgical intervention, showing non-inferiority of the new treatment (difference in proportion -0·016, 95% CI -0·15 to -0·18; p=0·0056). Invasive disease was found in five patients at primary or secondary surgery, but not in patients with per-protocol imiquimod treatment. There was no significant difference in HPV clearance, adverse events, and treatment satisfaction between study groups., Interpretation: Imiquimod is a safe, effective, and well accepted alternative to surgery for women with vHSIL and can be considered as first-line treatment., Funding: Austrian Science Fund and Austrian Gynaecological Oncology group., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The role of human papilloma virus (HPV) infections in oral carcinogenesis is an important topic of research in maxillofacial oncology. Nevertheless, the association between such infections in the oral cavity and the development of oral precancerous lesions remains unclear. The aim of this study was to evaluate the association between oral HPV infections and oral leukoplakia or erythroplakia., Study Design: The case control study included 118 patients with manifest oral leukoplakia or erythroplakia, who underwent surgical biopsy, including a histopathologic grading of the lesion, and 100 control patients without any oral lesions. HPV detection was achieved with a noninvasive brush smear method (Digene Cervical Sampler, Hybrid Capture II-Test). Logistic regression analysis was performed to assess the associations., Results: A significant association was found between high-risk oral HPV infection and the presence of oral premalignant lesions (P = .001). Among all other evaluated parameters, only smoking showed a significant association with the presence of oral lesions., Conclusions: Oral HPV infections may play a role in the pathogenesis of premalignant oral lesions., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: We sought to determine the validity of colposcopically directed cervical biopsies as a diagnostic test to define the degree of cervical intraepithelial neoplasia (CIN)., Study Design: In a prospective multicenter trial, patients undergoing excisional procedures of the transformation zone additionally had colposcopy and up to 3 guided cervical biopsies in a single procedure. Cervical biopsies were regarded as a diagnostic test to detect high-grade lesions (CIN 2,3), with the cone specimen as reference standard., Results: In all, 488 biopsies were performed in 244 cases, with 2 biopsies done in 192 cases. Cervical biopsies underestimated the severity of lesions in 46.7% of cases. Sensitivity, specificity, and positive and negative predictive values were 66.2% (95% confidence interval [CI], 59.4-72.3), 95.0% (95% CI, 83.5-98.6), 98.5% (95% CI, 94.8-99.6), and 35.5% (95% CI, 27.1-44.9), respectively., Conclusion: Our data suggest that cytologically suspected high-grade lesions (CIN 2,3) can be confirmed by biopsy in many cases, but they cannot be excluded., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Objective: Antibodies to human papillomavirus are indicative for previous human papillomavirus exposure. Human papillomavirus antibody reactivities to vulvar precancerous lesions were reported poorly, and the role of human papillomavirus in some of these lesions is still unclear., Study Design: In a direct enzyme-linked immunosorbent assay, serum samples from 126 healthy control subjects, 97 women with lichen sclerosus with or without squamous hyperplasia, 78 women with vulvar intraepithelial neoplasia, and 16 women with verrucous carcinoma were examined for immunoglobulin G and A antibodies to L1 virus-like particles of genital human papillomavirus types 6, 11, 16, 18, and 31, cutaneous human papillomavirus type 8, bovine papilloma virus, and cottontail rabbit papilloma virus., Results: In lichen sclerosus/squamous hyperplasia with atypia immunoglobulin G and A, antibody positivity rates to high-risk human papillomavirus virus-like particle types 16, 18, and 31 were significantly higher than in the control group and the lichen sclerosus/squamous hyperplasia group without atypia. In patients with vulvar intraepithelial neoplasia I, increased immunoglobulin G antibody prevalences with both high-risk and low-risk human papillomavirus-virus-like particles were detected; whereas in patients with vulvar intraepithelial neoplasia II/III, this was observed only with the human papillomavirus types 16, 18, and 31. When only reactivities with 2 genital human papillomavirus types were compared, percentages of positives to only 1 of these 2 types ranged between 43% and 82%, with regard to all respective positives., Conclusion: Our data support the role of high-risk human papillomavirus types, mainly human papillomavirus-16, in the pathogenesis of different vulvar lesions with atypia. Serologically, there are no indications that lichen sclerosus/squamous hyperplasia without atypia is associated with human papillomavirus, but high-risk human papillomavirus in lichen sclerosus/squamous hyperplasia with atypia could play a role in carcinogenesis. High antibody specificity was clearly demonstrated among 5 genital, 1 cutaneous human, and 2 animal papillomavirus types.

Objective: Infection with high-risk human papillomavirus (HPV) types such as HPV-16 is a major risk factor for the development of cervical cancer. HPV-16 capsid antibodies are detectable in approximately 50% of patients with HPV-16 DNA-positive cervical cancer. We investigated the prognostic significance of HPV capsid antibodies for survival in patients with cervical cancer in comparison with conventional clinicopathologic features such as staging, histologic grading, histology, age, and treatment modality., Study Design: Serum samples from 68 patients with cervical cancer and 65 healthy female control subjects were analyzed by enzyme-linked immunosorbent assay for HPV-specific immunoglobulin G (IgG) antibodies to baculovirus expressed HPV-6, HPV-11, HPV-16, and HPV-18 L1 virus-like particles (VLPs)., Results: HPV-16 L1 IgG antibodies were detectable in 6 of 65 (9%) of the control subjects and in 19 of 68 (28%) of the patients with cervical cancer (P =.007). In the subgroup of patients with HPV-16 DNA-positive cervical cancer (comprising 50% of the investigated samples), HPV-16 L1 antibodies were detected in 40%. HPV-16 L1 seropositivity was in univariate and multivariate analysis in addition to International Federation of Gynecology and Obstetrics stage, the only independent positive prognostic factor for overall survival (P =.01)., Conclusion: Antibodies to HPV-16 L1 were found to be an independent prognostic factor for overall survival in patients with cervical cancer. Thus, HPV-16 infection may be involved not only in oncogenesis but also in tumor development and behavior.