Editorial: What's new this month?

The management of vaginal intraepithelial neoplasia (VaIN) is complicated by its high recurrence rate and the significant drawbacks of conventional therapies, which range from poor adherence to drug regimens to the invasiveness of surgical procedures. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) represents a promising, non-invasive therapeutic modality for this condition. This study aimed to investigate the clinical efficacy, safety and prognosis of ALA-PDT in the treatment of human papillomavirus (HPV) infection complicated with VaIN. Between 1 January 2022 and 31 July 2024, a total of 156 patients diagnosed with VaIN were retrospectively identified through convenience sampling at the Obstetrics and Gynecology Clinic of the First Affiliated Hospital of Bengbu Medical University. Clinical treatment and follow-up data were collected for retrospective analysis. No significant differences were observed in cervical disease, lesion location, body mass index, HPV type or disease classification across different age groups (p > 0.05). Similarly, there were no statistically significant differences in the proportions of ThinPrep cytologic test negativity, HPV negativity, pathological recovery, patient satisfaction or adverse reactions among different age groups, HPV type groups or disease groups at 3, 6 and 12 months following the final treatment (p > 0.05). The results demonstrate that ALA-PDT is a safe and effective treatment for HPV infection combined with VaIN, with minimal side effects. Its therapeutic efficacy is not influenced by disease type, patient age group or HPV infection subtype.

This article investigates the effect of hypnosis on immunity and whether this is the key mechanism in the hypnotic treatment of the genital infection caused by human papillomavirus (HPV). HPV is the most common sexually transmitted disease and can lead to cervical and other cancers. Current medical treatments are aimed at tissue assault (acids, freezing, surgery). Medical wart clearance rates are only 30% to 70% and reoccurrence is common. Our research contrasted hypnosis-only with medical-only therapies, using both urban hospital and rural community samples. Both hypnosis and medical therapy resulted in a statistically significant (p < .04) reduction in areas and numbers of lesions. Yet, at the 12-week follow-up, complete clearance rates were 5 to 1 in favor of hypnosis.

We aim to 1) evaluate trends in adjuvant treatment of human papilloma virus (HPV)-related oropharyngeal cancer; 2) assess change in complications and functional outcomes over time; and 3) assess change in overall and disease-free survival (DFS) over time. Retrospective analysis. Charts of patients who underwent transoral robotic surgery for HPV-related oropharyngeal cancer between 2011 and 2019 were reviewed. Trend analysis was used to compare rate of adjuvant treatment over time. The Kaplan-Meier method was conducted to analyze overall survival (OS) and DFS. Three hundred and forty-two patients met inclusion criteria. One hundred and sixty-three (47.7%) patients underwent adjuvant radiation, and 90 (26.3%) patients underwent adjuvant chemoradiation. Rate of extranodular extension decreased significantly from 38.9% to 24.0% (P =.004). Rate of adjuvant therapy decreased significantly from 90.9% to 62.5% between 2011 and 2019 (P=.001). In patients who received adjuvant treatment, rate of adjuvant chemoradiation therapy decreased significantly from 40.0% to 20.0% (P < .0005). There was a decrease in rate of 1-year gastrostomy tube dependence in patients treated in 2015 to 2019 versus 2011 to 2014 (2.2% vs. 7.1%, P=.025). In 2011 to 2014, 2-year OS and DFS were 96% and 89%, respectively; in 2015 to 2019, 2-year OS and DFS were 96% and 94%, respectively. There was no difference in OS or DFS between the two time periods. The rate of adjuvant therapy, particularly chemotherapy, has decreased over time. One-year gastrostomy tube dependence rate has decreased significantly from 2011 to 2014 to 2015 to 2019. There was no change in OS and DFS over this time period. 3 Laryngoscope, 132:806-812, 2022.

54P Inhibition of ATM vs ATR in combination with radiotherapy affects cellular toxicity and expression of immune checkpoint molecules differently in HNSCC

Treatment of human papillomavirus (HPV)-associated vaginal lesions (vaginal intraepithelial neoplasia [VAIN]) can be expensive, tedious, and morbidity inducing. Imiquimod 5% cream, a safe and effective treatment of external genital warts, enhances the immune response to HPV infection. Imiquimod 5% cream was used to treat 56 young women with VAIN. One sachet of cream (0.25 g) was placed in the vagina with an applicator once weekly for 3 weeks (except for the first four patients, who were treated twice weekly). Thirty-six of the 42 patients (86%) available for follow-up were clear of VAIN lesions (as assessed by colposcopy) 1 week or later after the last dose of treatment. The remaining six patients cleared after a total of two (five patients) and three (one patient) treatment cycles. Vulvar or vestibular excoriation was reported in only 2 of 56 patients. No patients had vaginal ulceration. A very low dosing regimen of imiquimod 5% cream appears to be an effective and well-tolerated treatment for VAIN (primarily low grade.).

BACKGROUND: Anogenital warts are the most prevalent sexually transmitted infection (0.5%) among dermatological consultations. Cryotherapy with liquid nitrogen (LN) and therapy with trichloroacetic acid (TCA) are remarkable among the treatment strategies. OBJECTIVE: To evaluate the effectiveness of LN versus TCA in to treat penile warts in patients from a Brazilian public institution. METHODS: Open, parallel, randomized clinical trial. Following randomization, the warts were counted and submitted to cryotherapy (10s) or case therapy (TCA 80%) in each visit. The primary dependent variable was the lesion count before and after four weeks of treatment. We assessed the following variables: complete clearance, age, immunosuppression, smoking, topography, and education. RESULTS: 142 treatments were evaluated in 52 participants. There was a predominance of young adults, and the main topography affected was the penis shaft. The mean reduction rate per session was 48% for LN and 26% for TCA (p=0.11). 42 (81%) participants achieved complete clearance, with 39 (75%; 95% CI: 64-85%) reaching clearance in up to three sessions. Age was associated with a worse therapeutic response rate (ß =-0.09; p<0.01). CONCLUSIONS: LN and TCA proved to be effective to treat penile warts, without difference between treatments. Age was associated with a worse therapeutic response.

BackgroundInsights into the mechanisms associated with chemotherapy-resistance are important for implementation of therapeutic strategies and for unraveling the mode of action of chemotherapeutics. Although cidofovir (CDV) has proven efficacious in the treatment of human papillomavirus (HPV)-induced proliferation, no studies concerning the development of resistance to CDV in HPV-positive tumor cells have been performed yet.MethodsFrom the cervical carcinoma SiHa cells (SiHaparental), which are HPV-16 positive, cidofovir-resistant cells (SiHaCDV) were selected, and differential gene expression profiles were analyzed by means of microarrays. We examined in vitro phenotyping of resistant cells compared to parental cells as well as tumorigenicity and pathogenicity in a mouse-xenograft model.ResultsSiHaCDV had a resistant phenotype and a reduced growth both in vitro and in vivo. A markedly diminished inflammatory response (as measured by production of host- and tumor-derived cytokines and number of neutrophils and macrophages in spleen) was induced by SiHaCDV than by SiHaparental in the xenograft model. Gene expression profiling identified several genes with differential expression upon acquisition of CDV-resistance and pointed to a diminished induction of inflammatory response in SiHaCDV compared to SiHaparental.ConclusionsOur results indicate that acquisition of resistance to cidofovir in SiHa cells is linked to reduced pathogenicity. The present study contributes to our understanding on the antiproliferative effects of CDV and on the mechanisms involved, the inflammatory response playing a central role.

Topical imiquimod 5% cream (Aldara) is an immune response modulator that is indicated for the treatment of external anogenital warts, superficial basal cell carcinoma and actinic keratoses. The cream is applied two to five times per week for varying periods, depending on the indication. Topical imiquimod cream has also been evaluated in the treatment of several other skin conditions. Immunomodulatory therapy with topical imiquimod 5% is an effective option for the approved indications. The drug appears to be relatively well tolerated, with the option of breaks from treatment as required for local skin reactions (which are common). Systemic reactions have been reported. Treatment of human papillomavirus- and UV-associated skin lesions with topical imiquimod offers a noninvasive, tissue-sparing alternative to ablative treatment options. However, well designed trials of the sustained, long-term efficacy and tolerability of topical imiquimod versus those of common treatment approaches including surgery and other topical alternatives are required before the place of the drug in the management of these lesions can be finalised. Nonetheless, while other treatments for anogenital warts, superficial basal cell carcinoma or actinic keratoses are available, the advantages of self treatment linked with the demonstrated efficacy of topical imiquimod offer an attractive alternative for many patients.

Theta burst stimulation (TBS) is approved and widely used in the treatment of treatment resistant-major depression. More recently, accelerated protocols delivering multiple treatments per day have been shown to be efficacious and potentially enhance outcomes compared to once daily protocols. Meanwhile, bilateral treatment protocols have also been increasingly tested to enhance outcomes. Here, we examined the efficacy and safety of accelerated bilateral TBS in major depressive disorder (MDD). In this open label pilot study, 25 patients with MDD (60%: women; mean age (SD): 45.24 (12.22)) resistant to at least one antidepressant, received bilateral TBS, consisting of 5 sequential bilateral intermittent TBS (iTBS) (600 pulses) and continuous TBS (cTBS) (600 pulses) treatments delivered to the left and right dorsolateral prefrontal cortex (DLPFC), respectively, daily for 5days at 120% resting motor threshold. Outcome measures were post-treat treatment changes at day 5 and 2-weeks in Hamilton Depression Rating Scale (HDRS-17) scores and response (≥ 50% reduction from the baseline scores) and remission (≤ 7) rates. There was a significant reduction in HDRS scores at day 5 (p < 0.001) and 2-weeks post treatment (p < 0.001). The response rates increased from 20% at day 5 to 32% at 2-weeks post treatment suggesting delayed clinical effects. However, reduction in symptom scores between two post treatment endpoints was non-significant. 60% of patients could not tolerate the high intensity stimulation. No major adverse events occurred. Open label uncontrolled study with small sample size. These preliminary findings suggest that accelerated bilateral TBS may be clinically effective and safe for treatment resistant depression. Randomized sham-controlled trials are needed to establish the therapeutic role of accelerated bilateral TBS in depression.Trial registration: ClinicalTrials.gov, NCT10001858.

Cutaneous warts are caused by human papillomavirus (HPV). To date, more than 120 different types of HPV are known, of which 80 have been completely characterized. Prevalence studies on types of HPV present in cutaneous warts have been carried out in immunocompetent individuals and immunosuppressed organ allograft recipients, but not in human immunodeficiency virus (HIV)-positive patients. To determine the HPV types present in cutaneous warts of HIV-infected patients. Twenty-five biopsies of cutaneous warts from HIV-infected patients and 14 samples from control non-HIV-infected patients were studied. HPV detection was performed by polymerase chain reaction using two sets of primers: MY09/MY11 and RK91. The type of HPV was determined by restriction fragment length polymorphism analysis and direct sequencing of the amplified products. HPV DNA was detected in 64% of cutaneous warts from HIV-infected patients and in 79% of samples from the control group. The HPV types identified in HIV-infected patients were: HPV 2 (38%), 57 (31%), 27 (12%), 6 (12%) and 7 (6%). HPV 2/27/57 predominated in both groups, being present in 81% of lesions from HIV-infected patients and 82% of samples from non-HIV-infected patients. HPV 6, a genital HPV type rarely found in cutaneous lesions, was detected in two warts from HIV-infected patients and in one lesion of the immunocompetent group. HPV 7, characteristically associated with butcher's warts, and recently detected in oral and perioral lesions of HIV-infected patients, was found for the first time in a non-facial lesion of an HIV-infected patient. This is the first study evaluating the prevalence of HPV types in cutaneous warts of HIV-infected patients and immunocompetent individuals in Brazil.

Chapter 9 - Treatment of Human Papilloma Virus

Objective of this double-blind placebo-controlled study was to determine the efficacy of thermosensitive mucoadhesive gel loaded with 5-fluorouracil (5-FU):hydroxypropyl-s-cyclodextrin (HP-s-CD) complex via topical administration or intralesional injection for the treatment of human papilloma virus induced condyloma in 44 women. The diagnosis of human papilloma virus was established with clinical, histopathological and polymerase chain reaction techniques. Subjects were randomized into four parallel groups to evaluate topical or intralesional administration of drug-loaded or blank gel. The formulation used in the study consisted of 20% Pluronic PF 127 and 0.2% hydroxypropylmethylcellulose (HPMC) to render thermosensitive and mucoadhesive properties to the blank and drug-loaded gels. 5-FU was complexed to hydroxypropyl-s-cyclodextrin to improve its solubility and this complex was loaded into thermosensitive gel to obtain controlled release of the cytotoxic drug in administration site over a two-week period cure regimen aiming therapeutic efficacy with lower 5-FU doses. Complete response was achieved in 61% of patients through intralesional administration while topical administration resulted in only 29% complete cure. Relapse rates of all therapy groups were significantly low in the 6-month follow-up time.

A number of epidemiological studies have identified human papillomavirus (HPV) types 1, 2, 3, 4, 7, 10, 27, 57, and 65 in cutaneous common warts. However, identification of the HPV subtype by conventional polymerase chain reaction (PCR) is time consuming with its multi-step laboratory process. In this study, we aim to develop a specific one-step multiplex polymerase chain reaction method which capably identifies six different HPV genotypes related to common warts. By HPV DNA sequence analysis, 6 pairs of specific primers were designed from the intergenic regions of genes L1 to E6, and from genes E2 to L2. DNA sequence analysis with the L1 gene sequence of the sample was performed to measure the specificity of multiplex PCR. HPV-1, -2, -3, -4, -27, and -57 were identified without cross amplification in 109 out of 129 samples. The sensitivity and specificity of our set of primers in detecting HPV were 85% and 99.5%, respectively. For the 20 samples where HPV type was not identifiable by our batch of primer sets, multiplex PCR with an additional set of HPV primers was done, where 7 were found positive for HPV-7 or -65. Our results demonstrate that the newly designed multiplex PCR can rapidly detect the specific HPV subtype involved in common warts with high accuracy.

Spontaneous Regression of a Recalcitrant Wart after Bivalent Papillomavirus Vaccination

To assess attitude and knowledge among parents or guardians of 12-year-old girls about human papillomavirus (HPV), cervical cancer, and HPV vaccination. Material andMethods: A mail survey was sent to a randomized sample of 1,000 parents or guardians of 12-year-old girls from a cohort of total 2,092 girls born in 1995 and registered in the Icelandic National Register by the end of December 2007. Of the 994 eligible parents, 583 (59%) returned the questionnaire. Majority of the respondents were mothers who had two or three children. More than one-third of respondents had university education and 84% were married or living with a partner. Over two-thirds did not know that HPV causes cervical cancer and genital warts. Almost all (> 90%) would vaccinate theirs daughters with a HPV vaccine, 73% said they would vaccinate their sons, or themselves if the vaccine was effective for them. Only 11% believed HPV vaccination would increase promiscuity or decrease cervical screening attendance. In Iceland, willingness to vaccinate young girls with HPV vaccine is high, however, knowledge about HPV infections is limited.