To evaluate the safety, immunogenicity, and efficacy of INO-3107, a DNA immunotherapy designed to elicit targeted T-cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433).
Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO-3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9. Patients underwent surgical debulking within 14 days prior to first dose, with office laryngoscopy and staging at screening and weeks 6, 11, 26, and 52. Primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included frequency of surgical interventions post-INO-3107 and cellular immune responses.
An initial cohort of 21 patients was enrolled between October 2020 and August 2021. Fifteen (71.4%) patients had ≥1 TEAE; 11 (52.4%) were Grade 1, and 3 (14.3%) were Grade 3 (none treatment related). The most frequently reported TEAE was injection site or procedural pain (n = 8; 38.1%). Sixteen (76.2%) patients had fewer surgical interventions in the year following INO-3107 administration, with a median decrease of 3 interventions versus the preceding year. The RRP severity score, modified by Pransky, showed improvement from baseline to week 52. INO-3107 induced durable cellular responses against HPV-6 and HPV-11, with an increase in activated CD4 and CD8 T cells and CD8 cells with lytic potential.
The data suggest that INO-3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP.
3 Laryngoscope, 133:3087-3093, 2023.

Laryngeal papilloma (LP), which is associated with infection by human papillomavirus (HPV)-6 or -11, displays aggressive growth. The precise molecular mechanism underlying the tumorigenesis of LP has yet to be uncovered. Building on our earlier research into HPV-6, in this study, the viral gene expression of HPV-11 was investigated by quantitative PCR and DNA/RNA in situ hybridization. Additionally, newly developed antibodies against the E4 protein of HPV-6 and HPV-11 were evaluated by immunohistochemistry. The average viral load of HPV-11 in LP was 1.95 ± 0.66 × 105 copies/ng DNA, and 88% of HPV mRNA expression was found to be E4, E5a, and E5b mRNAs. According to RNA in situ hybridization, E4 and E5b mRNAs were expressed from the middle to upper part of the epithelium. E4 immunohistochemistry revealed a wide positive reaction in the upper cell layer in line with E4 mRNA expression. Other head and neck lesions with HPV-11 infection also showed a positive reaction in E4 immunohistochemistry. The distribution pattern of HPV DNA, viral mRNA, and E4 protein in LP with HPV-11 infection was quite similar to that of HPV-6. Therefore, it might be possible to apply these E4-specific antibodies in other functional studies as well as clinical applications, including targeted molecular therapies in patients with HPV-6 and HPV-11 infection.

Human papillomavirus (HPV) infection may lead to a series of lesions in the cervix. Distributions of HPV genotypes reveal that an increased prevalence of high-risk HPV (HR-HPV) is positively correlated with the severity of cervical lesions. Furthermore, persistent infection of HR-HPV is associated with a risk of cervical cancer. Considering the newly approval of the HPV vaccine in China and the prevalence of HPV distribution, which is meaningful for directing efforts for HPV vaccination, a more detailed understanding of HPV distribution is critical. This study aimed to investigate the overall prevalence of HPV and the age-specific features related to HPV distribution in the Jiangsu population.
We collected a total of 62,317 cervical cytological specimens from Xuzhou, Nanjing and Suzhou, which represent the northern, middle and southern regions of Jiangsu Province, respectively. All these samples were assigned to 6 groups based on participant age. HPV genotypes tests were performed by using a commercial kit which is designed for the detection of 17 high-risk HPV genotypes and 6 low-risk HPV genotypes.
The overall prevalence of HPV was up to 26.92% in Jiangsu Province. The most common high-risk genotype was HPV52 (5.09%), followed by HPV16, HPV58, HPV53, HPV51 and HPV68. The most prevalent low-risk genotype was HPV81 (2.70%), followed by HPV43, HPV42, HPV6, HPV11 and HPV83. Most infections were caused by HR-HPV, while single-genotype infection occurred more frequently than multiple-genotype infection. Regarding participant age, the overall infection rate of HPV was distributed in a U-shaped manner, with the highest peak in the younger than 20-year-old cohort. Additionally, significant variations were found between different cities, representing different regions of Jiangsu.
HPV prevalence is high in Jiangsu Province. The prevention of HPV-related diseases is challenging. Given the variation in HPV prevalence between ages groups and regions, a flexible HPV vaccination program, adjusted base on regional infection features, could have a beneficial effect in Jiangsu Province.

Cervical cancer is among the most common type of cancers in women and is associated with human papillomavirus (HPV) infection. Genital warts are also reported to be linked with HPV infection types 11 and 6. In turn, clinical characteristics and morphological features of warts may be useful in the prediction of prognosis and in making treatment decisions. Thus, we have investigated the association of high and low-risk HPVs genotype with genital wart risk, as well as pathological and cytological information in cases recruited from a population-based cohort study of 1380 patients. Patients infected with HPV genotype 6 or 11 had an increased risk of having warts, with OR of 2.34 (95% CI: 0.955-5.737, P = 0.06). Also, this association was enhanced in the presence of high plus low-risk HPV for having genital wart (OR: 2.814; 95%: 1.208-6.55, P = 0.017) and cases having high-risk HPV (OR: 2.329; 95% CI: 1.029-5.269, P = 0.042). Moreover, we observed patients with genital warts having CIN2/3, indicating the importance of informing the physician to the patient to prevent more severe lesions. Our data demonstrated that patients with both low/high-risk HPV types had an increased risk of developing genital warts and persistent infection with HPV was a necessary precursor for the increase in cervical lesions.

Human papillomavirus (HPV) types 6 and 11 are mainly associated with the development of genital warts and recurrent respiratory papillomatosis. We examined intratypic genetic variability of both viral types with the development of cervical cytologic abnormalities in Brazilian women.
We used PCR sequencing to characterize variants of HPVs 6 and/or 11 in cervical swabs from women in the Ludwig-McGill Cohort Study. We used a binomial generalized estimating equations (GEE) model with logit link to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between HPV 6 and 11 variants and cytologic abnormalities.
B1 and B3 HPV6 and A2 HPV11 variants were the most common isolates identified. Compared with HPV6-negative women, the ORs among women harboring HPV6 B1 or B3 variants were 6.3 (95% CI, 2.3-17.0) and 2.3 (95% CI, 0.6-9.7) for atypical cells of undetermined significance (ASCUS)/low squamous intraepithelial lesions (LSIL), respectively, and 1.7 (95% CI, 0.6-5.1) and 1.2 (95% CI, 0.3-4.7) for ASCUS/LSIL/high squamous intraepithelial lesions (HSIL). Respective ORs were 5.0 (95% CI, 1.7-14.6) and 2.8 (95% CI, 1.0-8.1) upon comparing women with HPV11 A2 variants to HPV11-negative women. All associations disappeared when adjusting for coinfections with high-risk HPV types.
Our data do not support an association between low-risk HPVs 6 and 11 genetic variability and cervical abnormalities.
Risk of cervical cytologic abnormalities is not affected by intratypic polymorphism in HPVs 6 and 11.

To determine external genital lesion (EGL) incidence -condyloma and penile intraepithelial neoplasia (PeIN)- and genital HPV-genotype progression to these EGLs.
Participants (healthy males 18- 74y from Cuernavaca, Mexico, recruited 2005-2009, n=954) underwent a questionnaire, anogenital examination, and sample collection every six months;including excision biopsy on suspicious EGL with histological confirmation.Linear array assay PCR characterized 37 high/low-risk HPV-DNA types. EGL incidence and cumulative incidence were calculated, the latter with Kaplan-Meier.
EGL incidence was 1.84 (95%CI=1.42-2.39) per 100-person-years (py); 2.9% (95%CI=1.9-4.2) 12-month cumulative EGL.Highest EGL inci- dence was found in men 18-30 years:1.99 (95%CI=1.22-3.25) per 100py. Seven subjects had PeIN I-III (four with HPV16). HPV11 most commonly progresses to condyloma (6-month cumulative incidence=44.4%, 95%CI=14.3-137.8). Subject with high-risk sexual behavior had higher EGL incidence.
In Mexico, anogenital HPV infection in men is high and can cause condyloma. Estimation of EGL magnitude and associated healthcare costs is necessary to assess the need for male anti-HPV vaccination.
Determinar incidencia de lesiones genitales externas (LGE) –condiloma y neoplasia intraepitelial del pene (NIP)– y progresión de genotipos deVPH a LGE.
Se aplicaron cuestionarios,examen anogenital y recolección de muestras cada seis meses a hombres sanos (18-74 años, de Cuernavaca, México, reclutados 2005-2009, n=954) con biopsia y confirmación histológica. Se caracteri- zaron 37 tipos de ADN-VPH; se calculó incidencia de LGE (cumulativa con Kaplan-Meier).
Incidencia de LGE=1.84 (IC95%=1.42-2.39) por 100-persona-años (pa); 2.9% (IC95%=1.9-4.2) LGE acumulativa a 12 meses. Mayor incidencia de LGE entre hombres 18-30 años; 1.99 (IC95%=1.22-3.25) por 100pa.Siete sujetos tuvieron NIP I-III. VPH-11 más comúnmente progresa a condiloma (incidencia acumulativa a seis meses=44.4%, IC95%=14.3-137.8). Los sujetos con comportamiento sexual de alto riesgo tuvieron mayor incidencia de LGE.
En México la infección anogenital conVPH es alta y puede causar condiloma. La estimación de magnitud de LGE y los costos sanitarios asociados se necesita para evaluar la necesidad de vacunación contra VPH en hombres.

BACKGROUND: Nitric oxide (NO), a free radical gas, is endogenously produced in human cells. In high concentration, NO neutralizes many disease-causing microbes. The topical investigational drug SB206 releases NO and has the potential to treat skin diseases caused by viruses. Genital warts (condyloma acuminata) are primarily caused by human papillomavirus (HPV) types 6 and 11. Available treatments have low tolerability and efficacy rates and are inconvenient for the patient. Genital warts can recur if HPV is incompletely eradicated during treatment.
OBJECTIVE: Topical SB206 (berdazimer sodium plus carboxymethyl cellulose hydrogel) was assessed for tolerability, safety, and efficacy for up to12 weeks in patients with external genital and/or perianal warts (EGW/PAW) in a phase 2, double-blind, randomized, dose-escalation study.
METHODS: Patients (N=108) were randomly assigned to SB206 or vehicle in a 3:1 ratio: SB206 4% once (QD) or twice daily (BID), 8% QD, 12% QD, or corresponding vehicle. Treatment duration was up to 84 days. The primary efficacy endpoint was complete clearance of baseline EGW/PAW at or before week 12. Pearson\'s Chi Square tests compared the efficacy of active vs vehicle treatments. Safety was assessed through adverse event and tolerability reports, physical examination findings, and clinical laboratory test results.
RESULTS: In the Intent-to-Treat population, the percentage of patients with complete clearance of baseline EGW/PAW at or before week 12 was higher for SB206 groups than for vehicle groups, with the greatest difference between SB206 12% QD (33.3%; P=0.010) and vehicle QD (4.3%).
CONCLUSIONS: Berdazimer sodium (SB206) plus hydrogel was efficacious and well tolerated in the treatment of EGW/PAW. J Drugs Dermatol. 2018;17(10):1100-1105.

To determine the incidence of anogenital warts (AGWs) in the Chinese general population, we compared the data from a prospective study and from the National Notifiable Disease Report System (NNDRS). A cohort study including 2378 women and 2309 men aged 18-55 years old enrolled from Liuzhou, China, was conducted with three scheduled visits at 6-month intervals from May 2014 to March 2016. And, a questionnaire survey was performed to collect the diagnosis history of AGWs at the enrollment visit. The data on reported AGW cases of Liuzhou in the NNDRS from 2006 to 2015 were also analyzed. Overall, the incidence rates of AGWs in the prospective study, in the self-reported diagnosis during past 12 months and in the NNDRS were 1.26 per 1000 person-years (95% confidence interval (CI): 0.16-2.37), 2.35 (95% CI: 1.17-4.20) and 0.183 (95% CI: 0.178-0.187), respectively. Human papillomavirus 6 or 11 were found in all the AGW biopsy samples (10/10). The onset time of AGWs in women was earlier, and the cumulative risk increased more quickly at a young age along with each subsequent younger birth cohort (P<0.0001), whereas slight differences were observed in the different male birth cohorts (P=0.0785). The sexual behavior of individuals and their sexual partners had a strong relationship with self-reported AGWs. Our study indicates that the incidence of AGWs in China is as high as that in developed countries, and the data based on the national surveillance system seriously underestimate the real disease burden of AGWs.

HPV-11 and HPV-6 are the etiological agents of about 90 % of genital warts (GWs). The intra-typic variability of HPV-11 and its association with infection persistence and GW development remains undetermined. Here, HPV infection in men (HIM) participants who had an HPV-11 genital swab and/or GW, preceded or not by a normal skin genital swab were analysed. Genomic variants were characterized by PCR-sequencing and classified within lineages (A, B) and sublineages (A1, A2, A3, A4). HPV-11 A2 variants were the most frequently detected in the genital swab samples from controls and in both genital swabs and GW samples from cases. The same HPV-11 variant was detected in the GW sample and its preceding genital swab. There was a lack of association between any particular HPV-11 variant and the increased risk for GW development.

BACKGROUND: This study aimed to detect the correlation between human papillomavirus (HPV) and spontaneous preterm labor in Egyptian women and its association to the human papilloma viral load and MPP2 gene expression.
METHODS: We performed an observational comparative case-control study in Department of Obstetric and Gynecology, Mansoura University Hospitals over women presented with spontaneous preterm labor, besides females admitted for giving birth at full term to detect conserved sequence in HPV-L1 gene (GP5/GP6) followed by genotype detection of high- and low-risk HPVs with quantification of the viral load and the MMP2 gene expression using real-time polymerase chain reaction (PCR).
RESULTS: The prevalence of HPV was 18.1% in preterm females, but only 4% in full-term women (p value = 0.019*). Twenty percent were PCR positive for HPV 16 and 40% for HPV 18 whereas none of the control was positive for any of the studied high-risk genotypes. Thirty percent were PCR positive for HPV 6 and 10% were positive for HPV 11. MMP2 gene expression was significantly higher in preterm than full term. Human papilloma viral load was found to be positively correlated to the rate of MMP2 expression and the gestational age was significantly related to the viral load and the rate of expression of MMP2 gene.
CONCLUSIONS: Human pabilloma virus especially high-risk genotypes was correlated to spontaneous preterm labor in Egyptian females through increasing early expression of MMP2 gene. The time of occurrence of preterm labor was affected by the viral load and so the rate of expression of MMP2 gene.