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This study aimed to estimate the epidemiologic and economic impact of a nonavalent human papillomavirus (HPV) vaccination program for 13- to 14-year-old females compared with that of the bivalent vaccine in Taiwan.A previously developed dynamic transmission model for the nonavalent HPV vaccine was adapted to the Taiwan setting. The natural history of cervical cancer and genital warts was simulated by the HPV model assuming an 80% vaccination coverage rate in girls aged 13 to 14 years of age with a 2-dose schedule for the nonavalent and bivalent HPV vaccines. A lifetime duration of vaccine protection was assumed for the HPV vaccine types.The model estimated that the nonavalent HPV vaccine would prevent an additional 15 951 cervical cancer cases, 6600 cervical cancer-related deaths, 176 702 grade 2 or grade 3 cervical intraepithelial neoplasia cases, 103 959 grade 1 cervical intraepithelial neoplasia cases, and 1 115 317 genital warts cases compared with the bivalent HPV vaccine. The nonavalent HPV vaccination program was projected to cost an additional New Taiwan dollars (NTD) 675.21 per person and to produce an additional 0.00271 quality-adjusted life-year per person over 100 years compared with the bivalent HPV vaccine. Thus, the incremental cost-effectiveness ratio of the nonavalent HPV vaccine versus the bivalent HPV vaccine was NTD 249 462/quality-adjusted life-year.A nonavalent HPV vaccination program for 13- to 14-year-old girls would have additional public health and economic impacts and would be highly cost-effective compared with the bivalent HPV vaccine, relative to per capita gross domestic product, which is estimated at NTD 746 526 for Taiwan.

The present guidelines aim to provide comprehensive information on genital condyloma acuminata, including the epidemiology, clinical features, diagnosis and management. The guidelines provide evidence-based recommendations on the diagnosis, prevention and treatment of genital condyloma acuminata in adults in Asia, including patients with HIV co-infection.A PubMed search was performed, using the keywords "condyloma acuminata", "anal wart", "anogenital wart", "genital wart" and "genital HPV". A total of 3031 results were found in publications during last six years. A careful review of the titles and abstracts was done to find all the studies pertaining to epidemiology, clinical features, diagnosis, treatment and prevention of condyloma acuminata.Various diagnostic procedures described are: 1. PCR (LE: 2b). 2. Serology (LE: 2b). 3. In-situ hybridization (LE: 3).1. Vaccination (LE: 1a): Quadrivalent vaccine reduced the frequency of anogenital warts in both vaccinated and unvaccinated contacts. According to the update Advisory Committee on Immunization Practices (ACIP) recommendations, the following protocol is recommended: (a). HPV vaccination at age 11 or 12 years for both males and females. (b). Catch-up vaccination for all persons through age 26 years. (c). Shared clinical decision-making regarding potential HPV vaccination for persons aged 27-45 years, who are at risk of new HPV infection. 2. Male circumcision (LE: 2a): conflicting evidence.In HIV-affected individuals, the course of HPV is more aggressive, with a greater risk of treatment resistance, increased chances of intraepithelial neoplasia as well as cancers.Physician administered. 1. Photodynamic therapy (LE: 1a). 2. Laser (LE: 2b). 3. Surgery (LE: 1a). 4. Electrosurgery (LE: 2c). 5. Cryotherapy (LE: 1b). 6. Immunotherapy (LE: 1b). 7. Podophyllin (LE: 1b). Provider administered. 1. Imiquimod 5%(LE: 1a). 2. Podophyllotoxin (LE: 1b). 3. Sinecatechins (LE: 1a). 4. Cidofovir (LE: 3). 5. 5- Fluorouracil (LE: 1a). 6. Interferon (LE: 1a).

Anogenital Condylomata Acuminata (AGCA) are caused by Human Papilloma Virus (HPV), which is one of the most common sexually transmitted illnesses in adults. Although commonly seen in the paediatric population, especially in the setting of immunocompromise, literature regarding transmission, viral type and management in this population is scant. The aim of this study was to assess the profile of patients presenting with anogenital warts in light of associated immunocompromise with Human Immunodeficiency Virus (HIV).Three years of patient records from Chis Hani Baragwanath Academic Hospital were reviewed (January 2017 - December 2019). Information collected included: gender, age of presentation, age at intervention, type and duration of medical treatment, type and number of surgical interventions, HIV status, and histology results. Fisher's and Pearson's test were used to assess correlation between immune status and surgical interventions necessary.In the time frame considered, we treated 66 patients with AGCA . The average age was 4 years old (1-14). HIV status was recorded in 30 patients (15 positive and 15 negative). Only one patient out of 66 had a history of sexual abuse. Whilst the proportion of patients who required surgical intervention in the HIV negative and HIV positive groups was equal (2:1), the total number of surgical interventions needed to achieve clearance was significantly more in those with HIV (p = 0.03).HIV positive patients with AGCA require more surgical interventions compared to HIV negative individuals. Further research will be conducted to ascertain the sub-type of HPV infection in this subset of patients and to assess if this impacts follow-up for future malignancy. Further research also needs to be conducted to ascertain whether surgical intervention should be instituted earlier in the treatment protocol for HIV positive children.

Summary Background The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16–26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. Methods The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16–23 years) or men who have sex with men (MSM; aged 16–26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov , NCT00090285 . Findings Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1–11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0–6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0–8·7) versus 137·3 (83·9–212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0–7·7) versus 140·4 (89·0–210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5–114·4) versus 906·2 (553·5–1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6–212·3] vs 0 cases per 10 000 person-years [0·0–13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0–215·7] vs 0 cases per 10 000 person-years [0·0–10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9–1289·1] vs 101·3 cases per 10 000 person-years [32·9–236·3]). No vaccine-related serious adverse events were reported. Interpretation The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. Funding Merck Sharp & Dohme.

Context The coronavirus disease 2019 (COVID-19) pandemic raised concerns about the safety of laparoscopy due to the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diffusion in surgical smoke. Although no case of SARS-CoV-2 contagion related to surgical smoke has been reported, several international surgical societies recommended caution or even discouraged the use of a laparoscopic approach. Objective To evaluate the risk of virus spread due to surgical smoke during surgical procedures. Evidence acquisition We searched PubMed and Scopus for eligible studies, including clinical and preclinical studies assessing the presence of any virus in the surgical smoke from any surgical procedure or experimental model. Evidence synthesis We identified 24 studies. No study was found investigating SARS-CoV-2 or any other coronavirus. About other viruses, hepatitis B virus was identified in the surgical smoke collected during different laparoscopic surgeries (colorectal resections, gastrectomies, and hepatic wedge resections). Other clinical studies suggested a consistent risk of transmission for human papillomavirus (HPV) in the surgical treatments of HPV-related disease (mainly genital warts, laryngeal papillomas, or cutaneous lesions). Preclinical studies showed conflicting results, but HPV was shown to have a high risk of transmission. Conclusions Although all the available data come from different viruses, considering that the SARS-CoV-2 virus has been shown in blood and stools, the theoretical risk of virus diffusion through surgical smoke cannot be excluded. Specific clinical studies are needed to understand the effective presence of the virus in the surgical smoke of different surgical procedures and its concentration. Meanwhile, adoption of all the required protective strategies, including preoperative patient nasopharyngeal swab for COVID-19, seems mandatory. Patient summary In this systematic review, we looked at the risk of virus spread from surgical smoke exposure during surgery. Although no study was found investigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or any other coronavirus, we found that the theoretical risk of virus diffusion through surgical smoke cannot be excluded.

Background: In 2009, both Norway and Denmark initiated routine quadrivalent human papillomavirus vaccination (qHPV) for 12-year-old girls; however, Denmark also introduced free-of-charge multi-cohort vaccination for older age groups in 2008. We aim to describe trends in genital warts (GWs) incidence rates (IRs) among men and women and qHPV vaccine coverage among women in Norway and Denmark in 2006–2015. Methods: We linked multiple national health registries in Norway and Denmark via national personal identifiers to access data on GWs incidence and qHPV vaccination among women and men aged 12–35 years residing in Norway and Denmark in 2006–2015. We calculated age-specific and age-standardized GWs IRs, GWs IR trends before (2006–2009) and after (2009–2015) the implementation of qHPV vaccination, and qHPV vaccine coverage among women. Results: In Norway and Denmark together, there were more than 200,000 cases of incident GWs and over 710,000 girls got at least one dose of qHPV vaccine during the study period. The total qHPV coverage in Norway and Denmark in 2015 was among women aged 12–35 years 24% and 70%, respectively. GWs IRs in Norway and Denmark decreased annually in 2009–2015 among women by 4.8% (95% confidence interval: 4.3 to 5.3) and 18.0% (95%CI: 17.5 to 18.6), respectively, and among men 1.9% (95%CI: 1.4 to 2.4) and 10.7% (95%CI: 10.3 to 11.2), respectively. In Denmark, GWs IRs decreased rapidly among both sexes and all age groups after qHPV vaccination, while Norway showed only a modest decrease. Conclusion: Rapid decline in HPV-related morbidity is feasible with high coverage of multi-cohort vaccination. However, the decision to vaccinate a single cohort of 12-years-old girls only will postpone HPV-related disease control by at least a decade. Thus countries planning HPV vaccination programs should also initiate multi-cohort vaccination for faster disease control.

Condyloma acuminatum (CA) of the anal canal is difficult to treat and subject to relapse.. We investigated the effects of aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with oral acitretin during therapy of refractory CA in the anal canal. We also conducted a clinical retrospective study for the treatment of intra-anal CA.A total of 101 patients diagnosed with intra-anal CA were enrolled. All patients underwent liquid nitrogen cryotherapy as a basic treatment until visible wart clearance. Patients were divided into two groups depending on the treatment modality after cryotherapy. ALA-PDT group with 51 patients was given ALA-PDT treatment, and ALA-PDT plus acitretin group with 50 patients was given ALA-PDT treatment combined with oral acitretin. The cure rate, recurrence rate, and adverse reactions of the two groups were analyzed and recorded.The cure rate in the ALA-PDT plus acitretin group was 94% (47/50), which was significantly higher than 80.4% (41/51) in ALA-PDT group. The recurrence rate in the ALA-PDT plus acitretin group was 6% (3/50), which was lower than 19.6% (10/51) in ALA-PDT group (P0.05).ALA-PDT combined with oral acitretin is effective and safe in the treatment of refractory CA in anal canal, and with further study may become an option for these patients.

Background Photodynamic therapy has been gaining popularity, particularly among young women. Therefore it is crucial to evaluate PDT for safety and its impact on fertility and delivery of healthy newborns. Objective The study analyzed the PDT treatment of 10 young women, who suffered from diseases of the vulva and cervix. The aim of the analysis was evaluating what impact PDT treatment had on their pregnancies and delivery. Methods 10 patients (22–32 years of age, 25.5 years of age on average) were treated with PDT in 2007-2014. 2 patients suffered from squamous cell hyperplasia, 2 patients from vulvar lichen sclerosus, 1 – genital warts, 1 - VIN I (current terminology: LSIL/Flat condyloma), 2 – CIN III (HSIL), 2 - CIN I (LSIL). The patients underwent photodynamic therapy (PDT). In the course of PDT the 5% 5- aminolevulinic acid was used in gel form three hours before irradiation. The affected areas were irradiated with a halogen lamp PhotoDyn 501 (590–760 nm) during a 10-min radiation treatment. The treatment was repeated weekly for 10 weeks. Results The median observation time period between the end of therapy and delivery was 3.92 years (2–7 years). None of the patients suffered from infertility. All patients gave birth to healthy, full-term infants. In case of one pregnancy cervical cerclage was needed. Two patients were treated for hypothyroidism caused by the Hashimoto disease. One patient had gestational diabetes. Two patients had already given birth to 2 children. Five patients gave birth by caesarean section. Conclusion Topical PDT selectively used for treating the diseases of the female reproductive organs was applied in our group of patients and proved to be a safe method. It had no apparent negative impact on female fertility and allowed these women to give birth to healthy children.

Condyloma acuminatum is a highly infectious disease caused by the human papillomavirus. Previous studies have shown that 5-aminolevulinic acid photodynamic therapy can inhibit proliferation of condyloma acuminatum keratinocytes. However, the effect of 5-aminolevulinic acid photodynamic therapy on condyloma acuminatum tissues has not been systematically studied. Here, we investigated possible molecular mechanisms of 5-aminolevulinic acid photodynamic therapy in the treatment of condyloma acuminatum and its effect on the expression of apoptosis inhibitors Bcl-2 and Survivin.Immunohistochemistry streptavidin-peroxidase was used to detect the expression of apoptosis inhibitors Bcl-2 and Survivin in condyloma acuminatum keratinocytes before and after the therapy.The positive expression rates of Bcl-2 and Survivin in condyloma acuminatum keratinocytes before treatment were 87.50% (42/48) and 79.16% (38/48), respectively. The positive expression rates of Bcl-2 and Survivin in condyloma acuminatum keratinocytes after treatment were 37.50% (18/48) and 41.67% (20/48), respectively. The positive expression intensity of Bcl-2 and Survivin in condyloma acuminatum keratinocytes before 5-aminolevulinic acid photodynamic therapy was mostly ++ to +++, and that after treatment was mostly - to +. There were statistically significant differences in the positive expression rate and the expression intensity of Bcl-2 and Survivin in the two groups before and after 5-aminolevulinic acid photodynamic therapy (P 0.001). There was a positive correlation between the expression of Bcl-2 and Survivin in condyloma acuminatum tissues after 5-aminolevulinic acid photodynamic therapy (r = 0.480, P 0.05).5-aminolevulinic acid photodynamic therapy may promote apoptosis of condyloma acuminatum cells by reducing the expression of Bcl-2 and Survivin, suggesting that this is potentially one of the molecular mechanisms of 5-aminolevulinic acid photodynamic therapy in the treatment of condyloma acuminatum.

Adjunctive immunohistochemistry tests for human papillomavirus (HPV) infection include p16 and Ki67 as well as the more recently discovered biomarkers importin-β, exportin-5, Mcl1, and PDL1. The purpose of this study was to compare the expression of these biomarkers in HPV infection due to the high-risk types such as HPVs 16, 18, 31, 33, 35, and 51 versus lesions that contain the low risk types HPV 2, 6 or 11. We studied 35 lesions with low risk HPV types (verruca vulgaris = 10 cases, condyloma acuminatum = 15 cases, CIN 1 with HPV 6/11 = 10 cases) and 25 CIN 1 or 2 lesions with a high-risk HPV type. The 25 high-risk positive CIN 1–2 cases had strong expression of the panel p16, Ki67, importin-β, exportin-5, Mcl1, and PDL1 where each protein localized to the cells in the parabasal aspect of the lesion. In comparison, neither p16, importin-β, exportin-5, Mcl1, nor PDL1 were increased in the epithelia of the lesions with the low risk HPV types; Ki67 showed variable expression. HPV viral capsid L1 protein and viral DNA were excellent markers of infection in the lesions with low risk types. Thus, p16, importin-β, exportin-5, Mcl1, and PDL1 are not only biomarkers of high-risk HPV infection but can also differentiate such lesions from those that contain low risk HPV types. Low risk HPV infections can be best differentiated from their mimics by viral L1 capsid detection and/or HPV DNA by in situ hybridization.

It is increasingly recognized that fundamental differences exist between high-risk and low-risk human papillomavirus (HPV) genotypes regarding interactions with the host. This study aims to join the recently emerging efforts to uncover these differences at the complete genome level and to study how they may influence the disease caused. Sixteen samples of thirteen patients with various HPV6-mediated benign mucosal disorders (nine recurrent respiratory papillomatoses with 2-8 recurrences, one condyloma acuminatum and three premalignant lesions of the genital mucosa) were sampled to determine the complete virus genomes. We collected the 197 HPV6 complete genomes deposited in the GenBank for cluster analysis to determine (sub)lineages. Genome polymorphisms were determined against the reference sequences of the (sub)lineages. Genome polymorphisms of the long control region (LCR) were tested for putative transcription factor binding sites; their functional analysis was performed by transient transfection of cloned whole LCRs into HEp-2 cells using a luciferase reporter system. Genomes from the same patients were always identical. Three, nine and one patients carried HPV6 lineage A, sublineage B1 and B2 variants, respectively. The three lineage A sequences were highly similar to each other, but distinct from the reference genome. A unique non-synonymous single nucleotide polymorphism (SNP) was found in the E5a open reading frame (ORF). Sublineage B1 genomes were more diverse, exhibited unique non-synonymous SNPs in the LCR and the E2/E4, L1, L2 ORFs. LCR activity of lineage A and sublineage B1 differed significantly; activity of one sublineage B1 LCR exhibiting two unique SNPs was significantly higher than that of other B1 LCR variants, close to the mean of LCR activities of lineage A variants. Different HPV6 lineages showed marked differences in variability patterns of the different genome regions. This may be involved in the differences in their distribution in different diseases or patient populations.

Background Human papilloma virus (HPV) infection and condyloma acuminatum (CA) in the genital area often exist in extensive and multi-point fashion. Laser ablation combined with topical photodynamic therapy (PDT) is a feasible approach for genital CA but its effectiveness and limitations need to be evaluated. Methods This single-arm prospective study consisted of 100 newly diagnosed CA cases of both sexes. All patients underwent laser ablation and then three times aminolaevulinic acid-based photodynamic therapy (ALA-PDT). The outcomes were evaluated and analyzed 3 months after the treatment. Results A total of 98 patients completed the study. Except for 6 patients (4 males and 2 females) showed some residual lesions other 92 patients (93.8%) showed complete cure. However, there were 18 patients (10 males and 8 females) showed new lesions near the treated areas. Although the HPV types of 18 patients before and after treatment were not completely consistent, 94.4% percent of patients (17/18) had the same HPV type as the primary lesion, which suggested that these late-onset CA might have latent infection or subclinical infection in the early stage of the disease but the length of the incubation period was longer. Conclusion Combination approach is effective in treating genital CA and preventing CA recurrence. But its limitations need to be recognized as the late-onset CA might occur near the treated area. The treatment plan needs to be optimized for multiple genital CA lesions.

Genital warts (GWs) are a risk factor for subsequent human papillomavirus (HPV)-related anogenital cancers. In this register-based, prospective cohort study, we estimated the risk of GWs in renal transplant recipients (RTRs) compared with a nontransplanted cohort. In a nationwide database, we identified first-time RTRs in Denmark during 1996 to 2015. For each RTR, 50 age- and sex-matched nontransplanted individuals were selected from the population registry. Information on GWs, sociodemographic characteristics, HPV vaccination, and other causes of immunosuppression was retrieved from registries. We estimated the cumulative incidence of GWs and used Cox regression to estimate hazard ratios (HR) of GWs in RTRs vs non-RTRs. We included 3268 RTRs and 162 910 non-RTRs without GWs 1 year before baseline. RTRs had higher hazard of GWs than non-RTRs (HR = 3.30; 95% confidence interval, 2.76-3.93, adjusted for sex, age, education, and income). The increased hazard of GWs compared with non-RTRs was more pronounced in female than in male RTRs. Although not statistically significant, the hazard tended to be higher in RTRs with functioning grafts compared with RTRs on dialysis after graft failure. The hazard of GWs was increased

The incidence of warts caused by human papilloma virus (HPV) infection is very high in the population. Photodynamic therapy (PDT), as an emerging method for wart treatment, has been demonstrated to be effective and safe by an increasing number of studies. This meta-analysis of previous literature aimed to investigate the potential of PDT as a first-line treatment for warts.To acquire proper and accurate information from relevant literature, the four databases PubMed, Embase, Web of Science and the Cochrane Library were searched. The wart clearance rate and patient cure rate were analysed as the primary outcomes. The recurrence rate, patient satisfaction and adverse reactions were also recorded.A total of 19 randomized controlled trials (RCTs) were included based on our search strategy. In the hand and foot wart group, PDT showed a statistically significant improvement in the wart clearance rate compared with placebo (P = 0.02), other lasers (P 0.0001), and cryotherapy (P 0.009). PDT use in the condyloma acuminatum group was not superior in terms of the wart clearance rate, with a value lower than that of the carbon dioxide (COOur study demonstrated that PDT provided several benefits, including but not limited to positive clinical outcomes, low recurrence rates and minor adverse reactions. The use of PDT as first-line therapy can be recommended.

Bowenoid papulosis (BP) is a rare infectious skin disease that occurs in sexually active young people. BP is associated with human papillomavirus (HPV)16 and 18 infections, spreads through sexual contact, and tends to become cancerous. Currently, there are different BP treatment methods, and few reports on the efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) (ALA-PDT). We compared the differences in the clearance and recurrence rates of BP between the ALA-PDT group and other groups, and explored methods to improve clinical effects and reduce lesion recurrence by combining clinical retrospective data.We enrolled patients who were diagnosed with bowel papulosis" between January 1, 2009, and December 31, 2020. Patient information, such as ID number, hospitalization number, admission time, name, age, gender, telephone number, admission record, discharge record, outpatient medical history, HPV type analysis, histopathological examination, and treatment plan were recorded. Outcomes were obtained and recorded through outpatient visits, telephone, and online follow-ups from patients who had reached the treatment endpoint. We compared and evaluated the differences in lesion clearance rate, lesion recurrence rate, and patient satisfaction between the ALA-PDT group and other groups using statistical analysis.The lesion clearance rate of the ALA-PDT group was significantly higher than that of the control group, the lesion recurrence rate was lower than that of the control group, and patient satisfaction was higher than that of the control group. The lesion clearance rate of the ALA-PDT group was higher than that of the microwave and radiofrequency groups, the lesion recurrence rate of the ALA-PDT group was significantly lower than that of the microwave and radiofrequency groups, and patient satisfaction was significantly higher than that of the microwave and radiofrequency groups. In the lesions of patients with BP, in addition to HPV16 and HPV18 types, other types were also detected, and most of them were mixed types of HPV infection. Age, sex, and duration of disease were not risk factors that affected BP recurrence.ALA-PDT for BP has the advantages of high lesion clearance rate, low lesion recurrence rate, and high patient satisfaction. ALA-PDT is worthy of recommendation as a preferred treatment plan for the treatment of BP.

Condyloma acuminatum (CA) is a sexually transmitted disease with a high recurrence rate due to the rapid replication of human papillomavirus (HPV) and its subtle immune escape mechanism, which makes the diagnosis and treatment of CA in the male urethra particularly difficult. This study aims to evaluate the efficacy of comprehensive treatments for male urethral CA after accurate localization of warts under ultrasound guidance.The study included 15 men with intraurethral CA. Before treatment, the urethra was examined by ultrasonography and HPV-PCR. After examination of the invisible urethral warts, wart curettage (penetrating operation with a special stainless steel medical curettage tool) combined with ALA-PDT was used for treatment. The ultrasound and HPV load were reviewed 1 week after treatment, and again at 1, 3, and 6 months after treatment.All patients achieved satisfactory results 1 week after the last treatment. The viral load of human papilloma was significantly reduced or turned negative, ultrasound imaging exploration showed no neoplasm in the urethra, and no obvious intraoperative or postoperative complications were observed. The side effects in patients included a mild burning or tingling sensation confined to the treated area. After a 6 month follow-up period, only 2 patient relapsed.The combined diagnosis and treatment of CA in the male urethra under the guidance of multi-mode ultrasound imaging is an effective, economical, safe, and well-tolerated treatment method.

Oral condyloma acuminatum (OCA) is a less prevalent subtype of condyloma acuminatum and is challenging to treat. We reported two cases of OCA successfully treated with 5-aminolevulinic acid photodynamic therapy (ALA-PDT). After three treatments spaced one week apart, both cases were completely cured without significant adverse reactions and were followed up for one year with no recurrence.

Background Human papillomavirus is a common sexually transmitted infection that may affect the oropharynx, genitalia, or anus. Some strains of this virus may cause bulky growths around the anus known as giant anal condylomas. These can become large, disfiguring, and may cause bleeding, as well as difficulty with defecation and hygiene. Surgical management is usually necessary for large condylomas, whereas office-based procedures are common for smaller lesions. It is unclear why some develop large anal margin tumors, whereas others develop limited disease. The aim of the present study was to evaluate for risk factors that may play a role in the development of extensive disease warranting operative management. Materials and methods A retrospective chart review of patients seen within the Anal Dysplasia Clinic at the Medical College of Wisconsin was undertaken. Clinic encounters for patients with anogenital condyloma were abstracted for demographic information, operative interventions, Human Immunodeficiency Virus status, and smoking history to determine risk factors that predicted operative intervention for giant anal condylomas. Results A total of 239 patients met inclusion criteria; 211 (88.3%) were male and 28 (11.7%) were female. Racial makeup of the cohort included 49% Caucasian, 38.9% African-American, 9.2% Hispanic, and 2.9% were identified as another ethnicity. One hundred forty-three patients (60.1%) were current or past smokers. One hundred ninety-eight (82.8%) patients tested positive for human immunodeficiency virus (HIV), whereas 41 (17.2%) were negative. Multiple linear regression identified only African-American race as predictive of greater disease burden. Conclusions African-American race was associated with increased size of anal condyloma. As the size of anal condylomas increase, management shifts from topical treatments to operative intervention. This is the first study to correlate race with burden of disease in the general population.

Background Condyloma acuminatum (CA) is a common sexually transmitted disease associated with human papilloma virus (HPV). CA occurring in the urethra is rare and has not been reported in male renal transplant recipients. In addition, despite immunosuppressive conditions and increased risk of HPV-related malignant neoplasms in transplant recipients, HPV testing in male transplant recipients has been uncommon. Here we report a case of urethral CA in a male deceased donor renal transplantation recipient and discuss the importance of HPV testing in male transplant recipients. Case Presentation A 33-year-old male deceased donor renal transplant recipient presented with miction pain 5 years after the transplantation. He reported repeated urinary tract infections with no sexual contact since the renal transplantation. Multiple papillary tumors in his penile urethra were detected by cystoscopy, and a biopsy sample was pathologically diagnosed with CA. Transurethral tumor resection was performed, and the tumors were completely resected. Additional HPV risk type screening with a urethral smear sample showed the prevalence of low-risk HPV. Although tacrolimus was switched to everolimus and imiquimod cream was administered, the tumors recurred 6 months after the resection, and a second resection was performed. No further recurrence has been observed for 1 year to date. Conclusion As the urethral CA was possibly related to immunosuppressive conditions and a risk for HPV-related malignant neoplasm, the case required careful diagnosis, including HPV risk type. The methodology of sampling for HPV testing in men has not been established. This case suggests the necessity for further discussion about HPV testing in male transplant recipients.

Condylomata acuminata (CA) or anogenital warts are benign proliferative lesions caused by low-risk human papillomaviruses (HPV). Treating CA can be very frustrating for patients and clinicians due to the high recurrence rates. Immunosuppression is associated with larger size of CA that are more frequently resistant to treatment. Surgical approaches tend to be poorly effective in the long-term because of high recurrence rates related to the persistence of HPV-infected cells. In our search to find an agent to treat intraurethral CA with minor or no side effects, we evaluated intraurethral cidofovir in two male patients, who were under immunosuppressing therapy due to organ transplantation and suffered from extensive urethral HPV lesions. Both patients underwent biopsy of the lesions and initial transurethral resection. In our first case, intraurethral cidofovir instillations were started after 2 months due to recurrence after surgical treatment. In our second case, intraurethral cidofovir was administered after surgery because of incomplete resection of extensive lesions. Because of persistent or rapidly recurrent lesions despite intraurethral cidofovir instillations, the first patient needed two additional surgical interventions while the second patient underwent one additional surgical intervention. After surgical intervention, both patients received again adjuvant cidofovir instillations without side effects. Over a period of 56 weeks, both patients received each a total of 28 instillations with cidofovir. Following 3.5 years (patient 1) of the last cidofovir instillation, no recurrences were observed in our first patient. Following 6 months of the last cidofovir instillation (patient 2), two very small recurrent lesions in the most distal part of the urethra were observed in our second patient for which he will receive a cycle of 6 cidofovir instillations in the near future. Intraurethral cidofovir is a safe, easy-to-use, well-tolerated and an effective adjuvant to surgery for extensive intraurethral CA in immunocompromised patients.

Background Anal canal condyloma acuminata are common, sexually transmitted lesions, most often caused by the human papillomavirus. The relatively high recurrence rate of anal canal condyloma acuminata can be attributed to the unsuccessful elimination of viruses in areas of subclinical and latent infection. This study aimed to observe and evaluate the effectiveness of 5-aminolevulinic acid-photodynamic therapy combined with monitoring of human papillomavirus load changes in patients with anal canal condyloma acuminata. Methods A total of 19 patients with anal genital warts were recruited for this study. Firstly, visible warts around the anus were removed. Next, an anoscope examination was performed. Human papillomavirus detection, using real-time polymerase chain reaction assays, was performed before every cycle of treatment. Absorbent cotton rolls soaked with a concentration of 20% 5-aminolevulinic acid were inserted into the anus for 3 h. Finally, photodynamic therapy was applied to the lesions. Each patient required multiple PDT sessions to achieve complete response. Results All patients achieved complete clinical remission one week after the last session of treatment, and human papillomavirus loads decreased significantly. Six months follow-up after completion of therapy, none of the patients had recurrence. Conclusions 5-aminolevulinic acid-photodynamic therapy is an effective and safe approach for anal canal condyloma acuminata. Dynamic human papillomavirus viral quantitative monitoring can aid in the evaluation of therapeutic effects and lead to better treatment outcomes.

Background Hyperthermia is an effective treatment against cancer and human papillomavirus (HPV) infection. Previous studies have shown that heat shock proteins are crucial to the action of hyperthermia. Objectives To examine the effects of hyperthermia in combination with DNAJA4-deficiency on human keratinocytes and Condyloma acumunatum (CA) tissues. Methods HaCaT cells were subjected to 44 °C (compared to 37 °C) waterbath for 30 min for stimulation. Foreskin or CA tissues obtained from patients undergoing circumcision or pathological examination were bisected and subjected to similar treatments. DNAJA4-knockout (KO) HaCaT cells were generated with CRISPR/Cas9 technology. mRNA and protein expressions were determined using rt-qPCR and western-blotting. Cell cycle distribution, apoptosis and senescence were analyzed by flow cytometry. Results DNAJA4 was induced in HaCaT cells, foreskin and CA tissues subjected to hyperthermia at both transcriptional and translational levels. NF-kB, 3 was activated by hyperthermia in HaCaT cells, and further enhanced by DNAJA4-deficiency. Transcription of TNF-α 4 ; IL-1B, 5 TNFAIP3 6 and IL-8 7 were induced in HaCaT cells subjected to hyperthermia. DNAJA4-knockout promoted transcriptions of TNF-α and IL-1B, whereas decreased that of TNFAIP3 and IL-8. Reduced cell survival, proliferation and viability were demonstrated using flow cytometry and MTS assays. Furthermore, NF-kB inhibitors reversed most of the phenotypes observed. Conclusions Hyperthermia reduced HaCaT cell proliferation and promoted cytokine expressions responsible for anti-viral activity, mainly through a NF-kB dependent pathway. DNAJA4-deficiency enhanced the activation of NF-kB by hyperthermia in HaCaT cells, indicating that DNAJA4 may be a promising therapeutic target for use in the treatment of cutaneous HPV infections.

Clinicians’ recommendation for the human papillomavirus (HPV) vaccine appears to be an important driver of parental decisions about vaccination. Our aim was to synthesize the best available evidence exploring the perceptions and experiences regarding HPV vaccination, from the perspective of the US clinician. We conducted a comprehensive literature search of Academic Search Complete, CINAHL Plus, Communication & Mass Media Complete, Consumer Health Complete (EBSCOhost), ERIC, Health and Psychosocial Instruments, MEDLINE with full text, and PsycINFO databases. We identified 60 eligible articles: 48 quantitative and 12 qualitative. We extracted the following information: study purpose, use of theory, location, inclusion criteria, and health care provider classification. Results were organized into 5 categories: 1) clinicians’ knowledge and beliefs about HPV and the HPV vaccine, 2) clinicians’ attitudes and beliefs about recommending HPV vaccines, 3) clinicians’ intention to recommend HPV vaccines, 4) clinicians’ professional practices regarding HPV vaccination, and 5) patient HPV vaccination rates. Although clinicians were generally supportive of HPV vaccination, there was a discrepancy between clinicians’ intentions, recommendation practices, and patient vaccination rates. Studies reported that clinicians tended not to provide strong, consistent recommendations, and were more likely to recommend HPV vaccines to girls versus boys and to older versus younger adolescents. Analyses revealed a number of facilitating factors and barriers to HPV vaccination at the clinician, parent/patient, and systems levels, including clinician knowledge, clinician beliefs, and office procedures that promote vaccination. This review provides an evidence base for multilevel interventions to improve clinician HPV vaccine recommendations and vaccination rates.

Background Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Methods Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. Results HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Conclusions Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV.

Objective To observe the clinical efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating vulval condylomata acuminata (CA) in pregnancy. Methods The clinical efficacies of ALA-PDT on 16 cases of CA in pregnancy as well as cryotherapy on 22 cases of CA in pregnancy were analyzed in this prospective study. Results The treatment group showed a wart clearance rate of 93.8% after 3 PDT treatments, while the control group showed a wart clearance rate of 72.7% after 3 cryotherapy treatments. After the 3-month follow-up period, the treatment group registered a recurrence rate of 6.3%, whereas the control group recorded a recurrence rate of 36.4%, indicating a statistically significant difference (χ2 = 4.674, p = 0.031 Conclusion ALA-PDT is safe and effective in treating CA in pregnancy.

Cutaneous secondary syphilis presents with various manifestations, including condyloma lata (confluented moist papules). This article reports an unusual case of oral condyloma lata. A 56-year-old man presented with a 2-month history of foreign body sensation and sore throat. Physical examination revealed a hypertrophic, reddish-brown, flat-topped, moist plaque in the right amygdaloid fossa. This raised clinical suspicion of lymphoma. However, further enquiry revealed that the patient had extramarital sexual history with a female sex worker. Rapid plasma regain and Treponema pallidum particle agglutination tests were both positive. The patient’s wife was diagnosed with early latent syphilis. Both the patient and his wife were treated with penicillin G benzathine, and the lesion in the male patient disappeared in 2 weeks. To the authors’ knowledge, a single condyloma lata in the amygdaloid fossa mimicking lymphoma has not been reported previously. Awareness of the usual manifestations of syphilis can avoid unnecessary biopsy, and early diagnosis and treatment may prevent irreversible complications. Partner notification is very important to reduce the risk of transmission, and persistent or recurrent infection.

Condylomata acuminata (CA) caused by human papillomavirus, often involves the external genitalia, perianal skin, and other moist mucous membranes. Urethral involvement is uncommon and little recognized, and usually limited to the distal 3 cm of the meatus. It is difficult to treat CA involving the urethra because of the anatomical location, risk of complications and recurrence. One effective method for the treatment of CA located at the urinary meatus is 5-aminolevulinic acid photodynamic therapy (ALA-PDT). However, experience of using this method for the treatment of whole urethral CA is still very limited. Herein, we treated a whole urethral CA successfully with photodynamic and holmium laser therapies. The case of a 25-year-old patient who underwent kidney transplant effected by intraurethral CA is presented and discussed. Catheter implantation and (or) immunosuppression treatment increases the risk of urethral condyloma acuminatum. The ALA-PDT is a safe, straightforward, effective, and well-tolerated treatment procedure for intraurethral CA. ALA-PDT combined with holmium laser treatment can successfully treat kidney transplant patients with intraurethral CA.

Objective Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts both men and women. However, there is limited data on its genomic characterization in mainland China. The aim of this study was to understand the complete genomic diversity of HPV6 from patients with condyloma acuminatum (CA) and to explore the prevalence of different variant lineages/sublineages in eastern China. Methods CA samples were collected in 3 hospitals in Shandong Province, China from January 2020 to March 2021. DNA extraction, PCR amplification, Sanger sequencing and sequence assembly were performed on HPV6-positive samples. The complete genomes obtained in this study were analyzed phylogenetically with global HPV6 sequences in GenBank database using MEGA 11. Results A total of 55 complete genomic sequences of HPV6 were obtained in this study. They were classified as HPV6 variant lineage A (n = 20), sublineage B1 (n = 34) and sublineage B3 (n = 1) by phylogenetic analysis. Sequence alignment showed E1, E5A, E5B, L1, L2, LCR were relatively highly variable regions for sublineage B1 whereas E1, E5A, L2 for lineage A. Both phylogenetic trees of lineage A and sublineage B1 composed of two main branches. Chinese sequences of lineage A segregated into the major branch while those in sublineage B1 belonged to both branches. Genomic divergence between sequences from China and other countries was 0.00% - 0.33% in lineage A and 0.00% - 0.40% in sublineage B1. Conclusions This is the first study on HPV variant lineages circulating in mainland China. The results revealed that lineage A and sublineage B1 were prevalent and they had different highly variable regions. Further surveillance is needed to understand the dynamic change of different variants in the population.

Interaction of the long control region (LCR) and the E2 protein of HPV11s was studied by in silico modelling and in vitro functional analysis. Genomes of HPV11s from fifteen (six known and nine novel) patients (two solitary papillomas, eleven respiratory papillomatoses of different severity, one condyloma acuminatum and one cervical atypia) were sequenced; E2 polymorphisms were analysed in silico by protein modelling. E2 and LCR variants were cloned into pcDNA3.1+ expression vector and into pALuc reporter vector, respectively, transfected to HEp2 cells alone or in different combinations and the luciferase activity was measured. In the E2, the ubiquitous polymorphism K308R caused stronger binding between the dimers but did not alter DNA binding; E2s with this polymorphism were significantly less efficient than the reference in promoting LCR activity. The unique polymorphism Q86K changed the negative surface charge of E2 (Q86) to positive (K86). The unique polymorphisms S245F and N247T in the hinge region disrupt a probable phosphorylation site in a RXXS motif targeted by protein kinase A and B, but do not affect directly the amino acids critical to nuclear transport. Both unique patterns partly restored the LCR activating potential disrupted by K308R. A unique E2/E4 ORF with a 58-bp deletion leading to a frameshift and an early stop codon resulted in a practically nonfunctional E2, and was associated with a papillomatosis with dysplasia. When testing existing LCR-E2 combinations, LCR with intrinsically lower enhancer capacity was only marginally activated by its E2 (R308 and the deletion mutant), and did not significantly exceed the activity of the reference LCR without E2. Combined with more potent LCRs associated with more severe disease, the activity was significantly higher, but still significantly lower than LCRs with reference E2. In summary, LCR-E2 interaction determined by their polymorphisms may explain, at least partly, differences in disease severity.

Background Multiple human papillomavirus infections are commonly encountered in genital warts. Infection can be eliminated using 5-aminolevulinic acid-based photodynamic therapy. The aim of this study was to identify the preponderant genotypes and patterns of human papillomavirus co-infection clearance during photodynamic therapy in patients with genital warts. Methods We conducted a retrospective study between January 2020 and February 2021 at two hospitals in Guangzhou, China. Human papillomavirus typing and quantitative detection were performed before starting treatment and after each session of photodynamic therapy. Results A total of 97 patients participated in the study. Co-infections with low-risk and high-risk types were common in genital warts. Types 6 was the most common type detected, followed by types 52, 11, 58, 51 and 56. Patients with multiple infections were more likely to have high-risk human papillomavirus infection. The viral load of high-risk human papillomavirus before treatment was significantly lower than that of low-risk human papillomavirus, and decreased faster during therapy. In addition, high-risk types were cleared more readily than low-risk types, and 51.4% of high-risk types were eliminated after three rounds of therapy. A transient increase in viral load, especially low-risk types, was observed after two sessions of therapy. Conclusions Low-risk human papillomavirus was preponderant in patients co-infected with low-risk and high-risk types. Photodynamic therapy effectively eliminated multiple human papillomavirus infections. The response to photodynamic therapy was mainly determined by the low-risk types in patients infected with combinations of low-risk and high-risk types.

Objectives: Puerto Rico (PR), is the fifth highest jurisdiction of the United States of America (US) with respect to HIV prevalence and the leading in cervical cancer incidence. This cross-sectional study describes the prevalence and correlates of cervical HPV infection among a clinic-based sample of 302 women living with HIV/AIDS in PR. Methods: Data collection included questionnaires, blood and cervical samples. Multivariable logistic regression models were used to estimate the magnitude of association (adjusted Prevalence odds ratio [aPOR]) between HPV cervical infection and other covariates. Results: Mean age of participants was 40.3 years (± 10.3 SD). The prevalence of HPV infection was 50.3%; 41.1% for low-risk types and 29.5% for high-risk types. Having ⥠10 lifetime sexual partners (aPOR = 2.10, 95% CI:1.02â4.29), an abnormal Pap (aPOR = 3.58, 95% CI:1.93â6.62), active genital warts (aPOR = 3.45, 95% CI:1.60â7.42), and CD4 counts ⤠200 (aPOR = 4.24, 95% CI: 1.67â10.78) were positively associated with any cervical HPV infection. Similar results were observed for HR HPV infection. Conclusions: A high burden of HPV co-infection exists among women living with HIV/AIDS in this population. Given the high incidence of HIV in PR and the higher risk of cervical cancer among women living with HIV/AIDS, HPV vaccination should be promoted in this population. Keywords: HIV, HPV, Cervix, Hispanic women, Puerto Rico

Background Topical Photodynamic therapy (PDT) is widely acknowledged for its safety and effectiveness in treating oncologic skin diseases such as basal cell carcinoma, actinic keratosis and squamous cell carcinoma in situ. Despite its broad applications in dermatology, this method is a relatively new therapeutic option for treating inflammatory/infectious skin diseases. Objectives To determine whether topical PDT is a safe and effective treatment option in treating treatment-recalcitrant dermatosis. Observations We presented one of each case of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget’s disease, where other treatment options were either ineffective or not feasible, then those patients underwent topical PDT and showed significant improvement with minimal side effects. Conclusions Topical PDT therapy may be applied in cases of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget’s disease, where other treatment has shown no or minimal improvement, or in whom ablative or invasive procedure is to be avoided or not well tolerated.

Background Cryotherapy is one of the most commonly used therapeutic modalities to treat anogenital warts (AGWs), but this treatment was not clearly established in the recent international recommendations. Objective To compare the efficacy and safety of cryotherapy versus other AGW treatments. Methods Through a systematic search of 12 electronic databases, we identified 11 randomized controlled trials, screened from database inception through October 2016, that met the inclusion criteria (including immunocompetent adults with AGWs receiving cryotherapy in 1 of the comparison groups). Primary endpoint was complete clearance of AGW. Risk-for-bias assessment was based on Cochrane Handbook recommendations. Meta-analyses used Review Manager v5.3 software. Results Cryotherapy efficacy did not appear to differ from that of trichloroacetic acid, podophyllin, or imiquimod. Electrosurgery was weakly associated with better AGW clearance than cryotherapy (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.65-0.99). Cryotherapy was associated with more immediate low-level adverse events (erythema, stinging, or irritation; RR 3.02, 95% CI 1.38-6.61) and immediate pain requiring oral analgesics (RR 2.11, 95% CI 1.07-4.17) but fewer erosions (RR 0.57, 95% CI 0.36-0.90). Limitations All but 1 randomized-controlled trial had a high risk for bias. Conclusion With low-level quality of the evidence, cryotherapy is an acceptable first-line therapy to treat AGWs.

Genital warts are the most common sexually transmitted disease and have a detrimental impact on quality of life. Genital warts could be prevented by prophylactic HPV vaccination. The objective was to study real-life benefit of opportunistic HPV vaccination on age and gender specific incidence of genital warts.We performed a register-based population cohort study from publicly funded health-care provider in Israel. The incidence of genital warts was assessed during three time frame intervals: 2006-2008 (pre-vaccination effect period) 2009-2012 (early post-vaccination effect period) and 2013-2015 (late post-vaccination effect period), with an average annual number of members of 1,765,481, 1,906,774 and 2,042,678 in the years 2006-2008, 2009-2012 and 2013-2015, respectively.Among females, annual incidence of genital warts per 100,000 women decreased from 210.43 to 161.71 (OR 0.76, 95%CI 0.71-0.82, p0.001) and to 146.8 (OR 0.69, 95%CI 0.66-0.72, p0.001) between pre-vaccination period and early and late post-vaccination periods, respectively. Among males, annual incidence of genital warts per 100,000 men decreased from 262.85 to 232.40 (OR 0.88, 95%CI 0.83-0.93, p0.001) and to 234.01 (OR 0.88, 95%CI 0.86-0.91, p0.001) between pre-vaccination period and early and late post-vaccination periods, respectively.There is a potential benefit in reducing incidence of genital warts even in opportunistic HPV vaccination structure. This information may be relevant for health-care providers in countries where national immunization programs do not include HPV vaccines.

The aims of this study were to determine the incidence of external genital lesions (EGLs), specifically histologically confirmed condyloma (genital warts) and Penile Intraepithelial Neoplasia (PeIN), and genital HPV infection progression to EGLs among healthy men aged 18–73 residing in Brazil. Subjects included 1118 men enrolled in the HPV Infection in Men (HIM) study between July 2005 and June 2009. At each visit, EGLs were biopsied and subjected to pathological evaluation. HPV status in genital swabs and biopsies was determined by Linear Array and INNO-LiPA, respectively. Age-specific EGLs incidence and the proportion and median time to EGL development were estimated. Kaplan–Meier cumulative incidence rates at 6, 12, and 24 months were determined. During follow-up, 73 men developed an incident EGL. Men could develop multiple EGLs and there were 36 men with condyloma, 27 men with lesions suggestive of condyloma, six men with PeIN, and 20 men with non-HPV lesions. HPV-positive men who developed EGLs were younger (p = 0.002) than men that did not develop lesions. Among the 815 men with HPV infection, 4% progressed to EGL with the same HPV detected in the swab. During follow up, 15.7% of genital HPV-6 and HPV-11 infections progressed to condyloma (median progression time of nine months for HPV-6 versus 6.8 months for HPV-11). Approximately 1% of HPV-16 infections progressed to PeIN with a median progression time of 25 months. HPV types covered by the 4-valent HPV vaccine were detected in 82.3% and 83.3% of condyloma and PeIN, respectively. The high burden of HPV and high frequency of progression to disease underscores the need to offer HPV prophylactic vaccination to men to reduce the overall burden of infection and diseases caused by HPV. Keywords: Men, Genital lesions, PeIN, Condyloma, HPV

Background The effect of 5-aminolevulinic acid photodynamic therapy on keratinocyte proliferation and apoptosis in condyloma acuminatum tissues was evaluated. Methods An immunohistochemical method and TdT-mediated dUTP nick end labeling were performed to detect the positive expression of the keratinocyte proliferation-related gene Ki-67 and apoptosis, respectively, in condyloma acuminatum tissues. Results Of 52 cases, 44 showed positive expression of Ki-67 in condyloma acuminatum keratinocytes before the treatment, with a positive expression rate of 84.62% (44/52), an expression strength of mostly ++ − +++, and a Ki-67 proliferation index of 80.26 ± 5.07%. After treatment, 22 cases showed positive expression of Ki-67 in condyloma acuminatum keratinocytes, with a positive expression rate of 42.31% (22/52), an expression strength of mostly − − ++, and a proliferation index of 42.67 ± 3.06%. The differences in the positive expression rate, expression strength, and proliferation index in the before- and after-treatment groups were statistically significant (χ2 = 20.070, P Conclusion 5-Aminolevulinic acid photodynamic therapy can inhibit the proliferation and promote the apoptosis of keratinocytes, and represents an effective mechanism for treating condyloma acuminatum.

Objectives To assess the effectiveness of the HPV vaccines in preventing genital warts in young women. Design Population-based study using health databases. Setting Valencian Community (Spain). Participants All girls and women aged 14–19 years who were registered in the Valencian Community between January 2009 and December 2014 (n = 279,787). Main outcome measures Incident cases of genital warts were defined as the first activation of diagnosis code ICD-9-CM 078.11 ( Condyloma acuminatum ) in primary care and outpatient clinics during the study period. Results There were 612 cases of genital warts. The overall incidence rate was 75.8/100,000 person-years (95% CrI 69.7–81.8). There was a decrease in genital warts when female candidates to be vaccinated with quadrivalent HPV vaccine reached the age of 18 (in 2012), compared to previous years. Incidence of genital warts in unvaccinated women and those who received the bivalent vaccine was higher than in girls and women who received the quadrivalent HPV vaccine. The effectiveness of a three-dose regimen of the quadrivalent HPV vaccine was 77% (95 CrI: 66–85%), whereas that of a single dose was 61% (95 CrI: 20–87%). No effectiveness was seen with a full vaccination course with the bivalent HPV vaccine. Conclusions Three doses of the quadrivalent HPV vaccine were effective against genital warts in our population. Moreover, with low vaccine coverage the incidence of genital warts decreased only in the vaccinated.

Genital HPV infections are widely prevalent. HPV can persist and be transmitted to partners even after warts are gone. The HPV genotype and viral load assay can reveal whether infections are persistent or latent, and it can serve as a predictor of infection clearance. Although numerous studies have demonstrated that photodynamic therapy (PDT) is effective against condyloma acuminata, there is no data on its effects on latent, persistent infections.A total of 20 patients with latent or subclinical HPV infection were evaluated. At each patient visit, polymerase chain reaction was used to identify HPV genotypes and measure the viral loads, which reflect the status of HPV infection. We administered 5-aminolevulinic acid (ALA)-based PDT weekly for patients with active infections, while no treatment was administered to patients with regressing infections.PDT treatment can effectively eliminate HPV, significantly reducing viral loads after three rounds of treatment (p 0.001). The rate of negative HPV DNA test results was higher in patients with latent or subclinical infections than in patients with genital warts after one round of PDT treatment.ALA-PDT can effectively eliminate latent or subclinical HPV infections. Additionally, our assay for identifying HPV genotypes and viral loads, which reflect the status of HPV infection, can accurately guide ALA-PDT treatment.

Background and objective The human papillomavirus (HPV) is the main causative agent of cancerous and precancerous lesions in cervical cancers. The infection detection is performed by cytological and histological examination. However, molecular testing for HPV infection remains necessary to distinguish nonspecific inflammatory lesions from HPV-related lesions. We aimed to compare cytological and histological diagnosis of HPV lesions and to confront histological findings with molecular detection of HPV by in situ hybridization (ISH). Material and methods A total of 2399 pap smears were collected between 1997 and 2002. Twenty-nine of them presented with lesions indicative of HPV infection. Colposcopy and biopsy were performed on 23 of these 29 pap smears, with a comparison of the cytological and histological findings. Molecular testing for HPV by ISH was performed on 11 pap smears. Results A 79% cytological and histological agreement was observed. ISH revealed the presence of the virus in seven case patients, amounting to a 63% histological and molecular agreement. Seven HPV genotypes were categorized (6-11-16-18-31-33-51). Conclusion HPV detection by ISH adds little to the diagnosis of HPV-associated lesions based on cytological and histological features. It, however, helps improve the specificity of the diagnosis and determine the viral genotype which, in turn, helps better define the lesion prognosis.

Introduction This study aimed to evaluate the early population impact of Ontario’s school-based human papillomavirus (HPV) vaccination program, implemented in September 2007 for grade 8 females, by comparing anogenital wart (AGW) health care utilization before and after vaccine program implementation, in program-eligible and program-ineligible cohorts, focusing on 15–26 year olds. Methods Using a retrospective longitudinal population-based study design, health administrative data were used to identify incident AGWs and total health service utilization (HSU) for AGWs for Ontario residents 15 years and older between April 1 2004 and March 31 2014. The study period was divided into two eras: the pre-vaccine program era and the vaccine program era. Negative binomial models were generated to analyze trends across time by age group and sex. We adjusted female rates for routine Papanicolaou (Pap) testing to address spillover effects of Pap smear policy changes on AGW diagnosis. Results Between fiscal years 2004 and 2013, AGW incidence decreased 2.6% on average per year in 15–17 year old females, and total HSU for AGWs decreased an average of 4.8% and 2.2% per year in 15–17 and 18–20 year old females. Comparing the vaccine era to the pre-vaccine era, AGW incidence decreased 6.5% in 18–20 year old females, and AGW HSU decreased 13.8%, 11.1%, and 10.0% in 15–17, 18–20, and 21–23 year old females respectively. In contrast, male AGW incidence rates increased an average of 4.1%, 2.8%, and 0.9% per year in 15–17, 21–23, and 24–26 year old males respectively. AGW incidence rates increased 12.2% in 15–17 year old males from the pre-vaccine to vaccine era. Conclusion The decline in AGW incidence and HSU in program-eligible females suggests the school-based HPV vaccination program has had an early population impact in Ontario. The increasing AGW incidence in males suggests no early evidence of herd effects in males.

Background More than 90% of anal condyloma is attributed to nonhigh risk strains of human papillomavirus (HPV), thus patients with anal condyloma do not necessarily undergo HPV serotyping unless they are immunocompromised (IC). We hypothesized that IC patients with anal condyloma have a higher risk of high-risk HPV and dysplasia than nonimmunocompromised (NIC) patients. Methods We performed a retrospective chart review of patients who underwent surgical treatment by a single surgeon for anal condyloma from 1/2000 to 1/2012. HPV serotyping was performed on all patient samples. We compared incidence of high-risk HPV and dysplasia in condyloma specimens from IC and NIC patients. Results High-risk HPV was identified in 14 specimens with serotypes 16, 18, 31, 33, 51, 52, and 67. Twenty-two cases (18.3%) had dysplasia. Invasive carcinoma was identified in one IC patient. The prevalence of dysplasia or high-risk HPV was not significantly different between IC and NIC groups. High-risk HPV was a significant independent predictor of dysplasia (odds ratio [OR] = 5.2; 95% CI = 1.24–21.62). Immune status, however, was not a significant predictor of high-risk HPV (OR = 1.11; 95% CI = 0.16–5.12) nor dysplasia (OR = 0.27; 95% CI = 0.037–1.17). Conclusions IC patients did not have a significantly higher prevalence or risk of high-risk HPV or dysplasia in our study. HPV typing of all condylomata, regardless of immune status, should be considered as it may help predict risk of neoplastic transformation or identify NIC patients with an increased risk of developing anal intraepithelial neoplasia.

Infections with human papillomavirus in the anogenital area result in warty, papillary, and condylomatous lesions. The giant anogenital wart is relatively uncommon. Treatment of giant wart is challenging, especially in the immunosuppressive population. Here, a patient with systemic lupus erythematosis had extensive, fast-growing, recurrent anogenital condylomatosis shaped as giant cauliflowers. We reported this case and the successful treatment of photodynamic therapy combined with surgical management. It provided the feasibility for surgical ablation combined with ALA-PDT performed for these kinds of challenging cases.

Condylomata acuminata (CA) is caused by human papillomavirus (HPV) infections of keratinocytes and is a common sexually transmitted disease. The main clinical feature and risk of CA is the high recurrence of genital warts formed by infected keratinocytes. Metabolic reprogramming of most types of mammalian cells including keratinocytes can provide energy and intermediates essential for their survival. Here, we report that HPV infection develops a hypoxic microenvironment in CA warts by inducing the accumulation of glycogen and increased glycogen metabolism in the infected keratinocytes in a hypoxia-inducible factor 1α (HIF-1α) -dependent pathway. Our in vitro studies show that the increased glycogen metabolism is essential for the survival and proliferation of keratinocytes. Regarding its mechanism of action, glycogenolysis generates glucose-1-phosphate that fluxes into the pentose phosphate pathway and, then, generates abundant nicotinamide adenine dinucleotide phosphate, thereby ensuring high levels of glutathione in keratinocytes under hypoxia. The abrogation of glycogen synthesis and glycogenolysis decreases the ratio of glutathione and glutathione disulfide and increases the level of ROS, further resulting in the impairment of keratinocyte survival. Collectively, our work offers an insight into the metabolic reprogramming in the development of CA and implies that the intervention of glycogen metabolism would be a promising therapeutic target for CA.

BACKGROUND: Hand-to-genital contact is hypothesized to be a transmission mode of HPV of genus Alphapapillomavirus. We compared the relative importance of hand-to-genital and genital-to-genital HPV transmission between sexual partners. METHODS: We recruited and followed-up female university students 18-24 years old and their male sexual partners in Montréal, Canada (2005-2011). Partners provided hand and genital samples, which we tested for DNA of 36 HPV types using PCR. We assessed predictors of incident type-specific HPV detections using Cox proportional hazards models. FINDINGS: 264 women and 291 men had valid hand samples. The hazard ratio (HR) of incident female genital HPV detection was 5·0 (95% confidence interval [CI] 1·5-16·4) when her partner was same type hand-positive vs -negative, but adjustment for his genital HPV status reduced the HR to 0·5 (95%CI 0·1-1·8). Similarly, the HR of incident male genital HPV detection was 17·9 (95%CI 7·9-38·5) when his partner was same type hand-positive vs negative, but adjustment for her genital HPV status reduced the HR to 2·3 (95%CI 0·9-6·2). Conversely, the HR of type-specific incident genital HPV detections associated with partner genital HPV positivity was 19·3 (95%CI 11·8-31·8) for females and 28·4 (95%CI 15·4-52·1) for males after adjustment for their hand HPV status. INTERPRETATION: Clinicians can reassure their patients that HPV transmission is unlikely to occur through hand-to-genital contact. The majority of genital HPV infections are likely caused by genital-to-genital sexual transmission. FUNDING: Canadian Institutes for Health Research, National Institutes of Health, Fonds de la Recherche en Santé du Québec, Merck & Co. Ltd.