Topical treatment for high-risk human papillomavirus: evidence gap persists.

Purpose of the study. Analysis of contemporary literature sources dedicated to the study of characteristics of high oncogenic risk human papillomavirus (HPV), associative links of the virus’s molecular-genetic parameters with the clinical and morphological characteristics of invasive cervical cancer (ICC).Materials and methods. A literature search was conducted in electronic databases including the National Center for Biotechnology Information Search database (PubMed/Medline), ResearchGate, Scopus, Web of Science, Cancer Tomorrow, Global cancer observatory, Cochrane Library, eLIBRARY, DisserCat. The search covered the period from 1990 to 2022 and utilized keywords in Russian and their English translations: cervical cancer, high oncogenic risk HPV, HPV status, HPV genotype, multiple infections, DNA integration, viral load. More than 120 full-text sources were studied, in which the analysis of possible correlations between the parameters of human papillomavirus infection and the clinical and morphological characteristics of cervical cancer was carried out. In review included data from 57 publications. Results. According to most authors, more than 88 % of patients with invasive ICC are HPV-infected. The etiological structure is dominated by HPV 16 (70–72 %), 18 (13–15 %), and 45 (5–7 %) types. Non-detection of HPV HR in cervical cancer is associated, including with a false negative result of the study.The literature analysis showed the presence of an association between HPV status and age, morphological form of the tumor, viral load, high oncogenic risk HPV genotype, presence of deep stromal invasion, and metastatic involvement of lymph nodes. With regard to such molecular genetic parameters of HPV HR as viral load and HPV DNA integration, associative relationship with prognostic important clinical indicators of cervical tumor – the stage of the disease, the loco-regional prevalence of the tumor process, the histological type of tumor – remains the subject of discussion.Conclusion. Many publications report a correlative link between HPV status and high oncogenic risk HPV genotype with such an important factor affecting ICC treatment outcomes as the morphological form of the tumor. Ambiguous conclusions on the presence of an association between a number of molecular-genetic parameters of HPV infection with the main prognostic factor – stage of the disease (due to the heterogeneity of samples, the use of different test systems, and the insufficiently complete account of the main parameters of HPV infection, especially data on viral DNA integration), make it advisable to conduct further research on a representative group of patients with homogeneous diagnostic protocols to determine the most complete spectrum of parameters of high oncogenic risk HPV. In addition, the conducted literature analysis showed the promise of searching for predictors of the effectiveness of specialized treatment of patients with ICC among such HPV infection parameters as HPV status, high oncogenic risk HPV genotype, and the significantly associated physical status of viral DNA.

Background: Cervical cancer is one of the most common types of cancer affecting women worldwide. Persistent HPV infection plays a major role in cervical cancer. The risk of cervical cancer has increased in parallel with the incidence of certain genotypes of human papilloma virus (HPV). Methods: The study was aimed to detect the distribution of HPV genotypes among cervical cancer patients from a specialized hospital in Dhaka, Bangladesh. HPV DNA testing was done by polymerase chain reaction (PCR) using SPF-10 broad-spectrum primers followed by genotyping by reverse hybridization using the INNO-LIPA genotyping system at the Department of Virology, Bangabandhu Sheikh Mujib Medical University, Dhaka. Results: HPV 16 was more prevalent (72.0%) in cervical cancer patients from Bangladesh followed by type 18 (6.0%) and 45 (2.0%). Genotype 16 and 18 alone and as co-infection were detected in 88.0% cases. Multiple HPV infection was found in 20% patients. Along with high risk (HR) HPV 16, 18 and 45 HR HPV 56, 39, 31 and 58 were also prevalent in multiple infections. Conclusion: Thus the study concluded that HR HPV 16 and HPV 18 were more prevalent genotypes among cervical cancer patients in a specialised hospital in Bangladesh. Along with HR HPV 16 and HPV 18, HR HPV 45, 56, 39, 31 and 58 were also prevalent Bangladesh Med Res Counc Bull 2019; 45: 86-92

Human papillomavirus (HPV) is considered a necessary cause of cervical cancer. The aim of the current study was to determine the burden of HPV infection among randomly sampled Danish women before the vaccine against HPV is implemented. Further we assessed the risk factor profile for prevalent high risk (HR) HPV infection and infection with multiple HR HPV types. In the present cross-sectional study, we used baseline data from a population-based cohort study where participants were interviewed and had a gynecological examination. Cervical samples were analyzed for HR HPV using Hybrid capture 2 in 10,544 women aged 20-29 years and 1443 women aged 40-50 years. Genotyping was performed using LiPA. The prevalence of HR HPV was 17.9% and 4.4% in women aged 20-29 years and 40-50 years, respectively. HPV16 was the most common HR type overall and among women with abnormal cytology. Multiple HPV types were highly prevalent, notably in the younger cohort. Lifetime number of sexual partners was the main risk factor for HR HPV infection (adj. OR = 2.8 and OR = 3.4 for > or =15 partners vs. < or =4 in respectively younger and older women), whereas number of recent sexual partners was only associated with risk in younger women. Number of partners, oral contraceptive use and self-reported chlamydia infection increased the risk of having multiple HR HPV types (compared to having a single HR HPV type). HR HPV infection was common among younger women, with HPV16 as the predominant type. We confirmed the importance of sexual activity for the risk of HR HPV infection. In addition, we found that sexual behavior also play an important role for the risk of having multiple HR HPV types.

Evidence of an etiological role for human papillomavirus (HPV) in Schneiderian inverted papillomas IP arose in the late 1980's; yet almost three decades later, the association between HPV and IP has yet to be universally accepted. This is probably due to the disparate HPV detection rates in IP reported in the literature. We analyzed the weight of published data in order to address the following questions: why do the HPV detection rates in IP vary so greatly? What is the relationship between low-risk (LR) and high-risk (HR) HPV types and HPV detection rates in IP? Is there a relationship between the presence and type of HPV in IP and recurrence and malignant progression? A search using the Pubmed search engine was performed to identify studies published in English from 01/87 through 12/06 using the MeSH terms ''HPV'' and ''Inverted", "Exophytic", "Oncocytic Schneiderian" or "Fungiform papilloma''. Data was abstracted from publications including histology, HPV target, HPV type, method of detection, etc. HPV results were stratified by histology and other variables. Tests for heterogeneity (between-study variability) were conducted, and weighted prevalence (WP) estimates and 95% confidence intervals (CI) were calculated using a random-effects inverse-variance model stratified on study. The association between HPV IP recurrence was estimated by random-effects inverse-variance weighted odds ratio (OR). Weighted estimates revealed similar detection rates across detection methods, 26.8% (95%CI 16.4-37.2%) by ISH, 25.2% (95%CI 14.7-35.6%) by consensus PCR, and 23.6% (95%CI 12.2-35.0%) by type-specific PCR. A preponderance of HPV 6/11 is found in IP as compared to HPV 16/18; the overall unadjusted ratio of LR to high-risk HR HPV types is 2.8:1 The HPV detection rates significantly increase (Wald t-test P < 0.02) in IPs with high-grade dysplasia (WP 55.8%, 95%CI 30.5-81.0%) and carcinoma (WP 55.1%, 95%CI 37.0-73.2%) as compared to IPs with no dysplasia or mild dysplasia (WP 22.3%, 95%CI 15.9-28.6%). Furthermore, the preponderance of LR HPV in benign IP (ratio LR/HR = 4.8:1) shifts in dysplastic and malignant IP. The LR/HR ratio is 1.1:1 for IPs with high-grade dysplasias, this ratio is inverted to favor HR HPV (1:2.4) for malignant IP. Recurrences developed in 44 of 236 patients; HPV was detected in 27 of 44 IPs (WP 57.9%, 95%CI 31.6-84.2%) that developed recurrences and in 24 of 192 IPs (WP 9.7%, 95%CI 4.4-15.0%) that did not develop recurrence. The presence of HPV was significantly associated with the likelihood of developing recurrence (weighted OR of 10.2, 95%CI 3.2-32.8). We hypothesize that LR HPV may induce IP formation, and then are lost as infected cells are shed, as a "hit and run" phenomenon. HPV detection rates increase in dysplastic IP and SCC-ex-IP with increasing ratio of HR to LR HPV types, compared to nondysplastic IP. We believe that one explanation for the variation in HPV detection rates between different studies may be the actual histologic composition of the cohort. That is, if one series contains a higher frequency of dysplastic and malignant IP, it may have a higher detection rate than another series which contains only nondysplastic IP. We hypothesize that the higher rates of HPV detection in dysplastic and malignant IP may be related to HPV integration. The implication of this is that HPV sub-type testing may identify patients at risk for recurrence, or progression to dysplasia and malignancy, and thus may impact surveillance protocols.

Background: High-risk (HR) Human Papillomavirus (HPV) is an established cause of cervical cancer. HPV genotype detection is significant in preventing cervical cancers through targeted vaccination our study aimed to identify HRHPV16/18 and non 16/18 in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). Methods: A retrospective study was performed at Pathology Department, BMSI, JPMC, Karachi. About 96 cases of CIN and SCC were included. Analysis of HPV genotypes was performed by DNA extraction, PCR amplification and flow-through hybridization technique. The probes used had a cluster of 13 HRHPV into a group of 3 as HPV HR 1, 2 and 3. Chi square/ Fischer Exact test were applied to observe the association of morphological types of the lesion and expression of HPV genotypes. Results: HPV DNA positivity was 44% in our series. HPV HR 1 was observed in majority of cases (61.9%), followed by HPV 16 in 23.8%, HPV HR 3 in 9.5%, and HPV HR 2 in 4.7% cases respectively. The unique finding was absence of HPV 18 in the series. High grade lesions and invasive cancers showed positivity for HPV HR 1 and HPV 16, while low grade lesions were positive for HPV HR 1, 2 and 3 respectively. Conclusion: HPV HR1 are major causative agents for low and high grade intraepithelial and invasive SCC, followed by HPV 16. Absence of HPV 18 was the novel finding. Our results differ from studies within and outside the region, suggestive of diversified genetic makeup and impact of detection techniques on results.

Objective To determine the genotypes of human papillomavirus (HPV) and to estimate their correlations with recurrence of perianal and anal condyloma acuminatum (CA) among men who have sex with men (MSM) in Shanghai.Methods Tissue specimens were obtained from the lesions of perianal or anal CA in 57 MSM.Flow-through hybridization and gene chip were used to determine the genotypes of HPV in these specimens.Follow-up was carried out to observe the recurrence of CA in these patients after CO2 laser treatment.Results Of the 57 specimens,56 (98.2％) were positive for HPV,and a total of 11 HPV subtypes were identified.The predominant genotypes were HPV 11 (42 cases,75％ ) and HPV 6 (30 cases,53.6％),sequentially followed by HPV 16 (8 cases,14.3％),HPV 18 (4 cases,7.1％),HPV 33 (2 cases,3.6％),HPV 59(2 cases,3.6％),HPV cp8304 (2 cases,3.6％),HPV 31 (1 case,1.8％) and HPV 35 (1 case,1.8％).Of the HPV-positive specimens,64.3％ (36/56) harbored low risk HPV types (11 and/or 6),and 35.7 ％ (20/56) harbored high risk HPV types.Among the 20 specimens positive for high risk HPV,17 (85％) harbored both low risk- and high risk-HPV genotypes.During the 6-month follow-up after CO2 laser treatment,recurrence was observed in 95％ of patients with high risk HPV and 66.7％ of patients with low risk HPV (P ＜ 0.05).Conclusions Among MSM with perianal and anal CA in Shanghai,the predominant genotypes of HPV are low risk types 11 and 6; high risk HPV infection is usually complicated by low risk HPV infection; the recurrence of CA is higher in patients with high risk HPV than in those with low risk HPV. Key words: Condylomata acuminata; Human papillomavirus; Homosexuality; Male

BackgroundIn 2017, Armenia introduced a national human papillomavirus (HPV) vaccination programme with a quadrivalent vaccine at age 14 years. Successful implementation of the programme was affected by social media campaigns aiming to discredit its efficacy and safety, the COVID-19 pandemic, and local armed conflicts. To support national public health stakeholders, we initiated a series of studies to provide local evidence on the burden of HPV infection.MethodsTwo cross-sectional HPV prevalence surveys among unvaccinated birth-cohorts of women were conducted: a urine-based survey (UBS) targeted women aged 17–21 years, and a cell-based survey (CBS) targeted women aged 21–39 years. In addition, we collected a series of invasive cervical cancer (CC) case laboratory samples to assess the attributable proportion of high-risk (HR) HPV types to estimate the impact of HPV vaccination in Armenia.FindingsIn the UBS and the CBS, 2485 and 3017 women were included, respectively. In the UBS, 110 (4.5 %) women were positive for any HPV type, 72 (2.9 %) of which were HR HPV and 29 (1.2 %) were HPV16/18. In the CBS, 553 (18 %) were positive for any HPV type, 326 (11 %) of which were HR HPV, and 99 (3.3 %) were HPV16/18. In the CC series, HPV16/18 accounted for 71 % of all HR HPV infections, HPV 31, 33, 45, 52, and 58 accounted for an extra 18 %. The remaining HR types accounted for 11 % of all CC infected by HR HPV. The corresponding predicted cumulative 10-year CC incidence among 20–24, 25–34, and 35–44-year age group, was 0.3 %, 1.3 %, and 3.8 %, respectively.InterpretationOur findings provide a picture of the HPV infection and future cervical cancer burden among unvaccinated young and adult women in urban areas of Armenia and can inform context-specific vaccination and screening policies.

ObjectiveThe objective of the present study was to assess the prevalence and type-specific distribution of cervical high-risk (HR) human papillomavirus (HPV) among women with normal and abnormal cytology, and to...

ObjectiveThe aim of this study was to determine the prevalence of high-risk (HR) and vaccine-type human papillomavirus (HPV) infection among Thai schoolgirls who were not included in the national HPV immunization program. MethodsCross-sectional surveys were conducted among grade 10 (15–16 years old) and grade 12 (17–18 years old) schoolgirls in two provinces of Thailand. Urine samples were collected using the Colli-PeeⓇ device from November 2018 to February 2019. The samples were initially tested using CobasⓇ 4800. Subsequently, all Cobas-positive samples and 1:1 matched Cobas-negative samples were tested by AnyplexⓇ assay. Prevalences of any HPV, any HR HPV, vaccine-type HPV, and individual HR HPV types were estimated by school grade. ResultsPrevalences of any HPV and any HR HPV were 11.6% and 8.6% for grade 10, and 18.5% and 12.4% for grade 12 schoolgirls, respectively. Prevalences of bivalent vaccine-type HPV infection in grades 10 and 12 were 3.4% and 4.5%, respectively. Prevalences of quadrivalent and nonavalent vaccine-type HPV infections were 4.0%/6.6% and 6.4%/10.4% in grades 10 and 12, respectively. HPV16 was the most common type detected, followed by HPV58, 51, and 52. Circulating HR HPV types were similar between the school grades. ConclusionA substantial burden of HR HPV infections was found among unvaccinated high school girls in Thailand.

It is estimated that 79 million people in the US are currently infected with human papillomavirus (HPV). There are more than 200 different HPV types that are common worldwide. HPV types are categorized as either high risk (HR) or low risk (LR). LR types, such as HPV 6 and HPV 11, can cause genital warts or squamous papillomas of the oral cavity, while persistent infection with HR HPV types can induce cervical, anal, or head and neck cancers. Episomal HPV DNA can be detected in advanced stages of cancer. HPV integration in the host genome drives oncogenesis by the expression of the two major viral oncogenes, E6 and E7, which abrogate cell cycle checkpoints, promote cellular proliferation, and cause progressive genetic instability. Hence, screening for the presence of E6/E7 RNA transcripts expression is considered the gold standard for confirming active HPV infection. Early detection of active HPV is critical for better understanding of prognosis and therapeutics. So far, detection of integrated HPV DNA in tissue specimens has been challenging. A novel, cost-effective, in situ hybridization (ISH) detection assay has been developed using two sets of HPV probes with enhanced signaling, termed hyper probes. The Hyper HPV D probe detects HR HPV DNA and the Hyper HPV DR probe can simultaneously detect DNA and E6/E7 RNA of HR HPV subtypes in cancer cell lines and formalin fixed paraffin embedded (FFPE) biopsy specimens. The probes were tested on cervical carcinoma SiHa cells containing 1-3 copies of integrated DNA of HPV 16 and HPV negative cervical cancer C33A cell line. The Hyper HPV DR probe resulted in 1-3 puncta in more than 90% of SiHa cell nuclei, indicating integrated copies of HPV DNA into the host genome. There was also the additional presence of a diffuse signal which was abolished by pretreating SiHa cells with RNase. These data suggest the diffuse signal corresponds to E6/E7 mRNA expression. No signals were detected in HPV negative C33A cells. When cells were stained with Hyper HPV D probes, only punctate signals in nuclei of SiHa cells was present and no signal was evident in C33A control cells. Additionally, human cervical and anal FFPE biopsies were analyzed. Simultaneous presence of both punctate signals and diffuse signals were detected when using Hyper HPV DR probes in HR HPV infected tissues, while only punctate signal was detected when using HPV D hyper probes. The signal from the hyper probes was significantly stronger when compared to other commercially available HPV detection kits. Moreover, other commercially available kits failed to detect low copy of integrated HPV. In conclusion, these data demonstrate the Hyper HPV probes can reliably detect low copies of HPV DNA integrated in the host genome and the presence of HPV mRNA using ISH in HPV infected cells. Citation Format: Maurizio Mauro, Richard Delle Bovi, Jack Coleman. Sensitive detection of integrated HPV in carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1401.

Objectives: To estimate prevalence and determinants of high risk (HR) human papillomavirus (HPV) by country of origin in women attending a family planning centre (FPC) in Alicante, Spain. Methods: Cross...

BackgroundHuman papillomavirus (HPV)–attributable oropharyngeal cancer (HPV-OPC) incidence is increasing in many high-income countries among men. Factors associated with oral HPV persistence, the precursor of HPV-OPC, are unknown. Data from the HPV Infection in Men (HIM) Study, which followed participants >7 years, were utilized to examine rates of persistence and associated factors.MethodsOral gargle samples from 3095 HIM study participants were HPV genotyped using the SPF10 PCR-DEIA-LiPA25 assay (DDL Diagnostic Laboratory). Oral HPV persistence for individual and grouped high-risk HPV types among 184 men positive for any high-risk HPV at their oral baseline visit was assessed at 6-month intervals. Factors associated with grouped high-risk HPV/HPV16 persistence were examined using logistic regression. Kaplan-Meier curves were constructed to examine median time to HPV clearance overall, and by selected risk factors.ResultsAmong the 7 HPV vaccine types, HPV33 had the longest median duration (7.6 months) followed by HPV16 and HPV45 (6.4 months). 10–30% of oral high-risk HPV infections persisted ≥24 months. Six months’ persistence of oral high-risk HPV infections was positively associated with age and gingivitis and negatively with lifetime number of sexual partners, while 12 months’ persistence was only inversely associated with lifetime number of sexual partners. Oral HPV16 persistence was positively associated with baseline HPV16 L1 antibody status.ConclusionsEighteen percent of HPV16 infections persisted beyond 24 months, potentially conferring higher risk of HPV-OPC among these men. Older age appears to be an important factor associated with oral high-risk HPV persistence. More studies among healthy men are required to understand the progression of oral HPV infection to HPV-OPC.

Background Human papilloma virus (HPV)-associated head and neck cancer is now recognized as a distinct clinical entity from HPV-negative tumors, which are primarily associated with tobacco and alcohol exposure.Little is known, however, about the behavior of HPV-associated oropharynx (OP) and oral cavity (OC) SCCs as two distinct cancers and how sex affects the overall survival (OS) in these two cancers. The objective of our study is to determine if sex is associated with overall survival (OS) in patients with high-risk human papillomavirus (HPV)-positive and HPV-negative squamous cell carcinomas (SCC) in the oropharynx and oral cavity sites.MethodsThis is a retrospective cohort study using a national database. Data were extracted from the National Cancer Database (NCDB) of patients diagnosed with OP or OC SCC from 2010 to 2014. Univariate and multivariate survival analyses were conducted with chi-square tests, Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards multivariable modeling.ResultsA total of 30,707 patients (13,694 OP HPV-associated, 7933 OP HPV-, 1220 OC HPV-associated, 7860 OC HPV-) were identified. In all four groups, women tended to be older and have lower T and N clinical classification than men. Though there were no significant differences in OS between the sexes in OP HPV-associated cancers, female sex was associated with worse OS in OP HPV- cancers (HR: 1.15; 95% CI 1.04–1.28, p = 0.004), whereas it was associated with improved OS in OC HPV-associated and HPV- cancers (HPV-associated: HR: 0.71; 95% CI 0.50–0.99, p = 0.048; HPV-: HR: 0.87; 95% CI 0.78–0.95, p = 0.004).ConclusionThe effect of sex on OS in OC and OP SCC appears to vary based on tumor location and HPV status. While the source of this difference in prognostic association is unclear, it may be related to an emerging difference in the biology of HPV carcinogenesis in these locations.

Objective : The detection of high-risk human papilloma virus (HPV) allows us to predict the presence and future development of cervical intraepithelial neoplasia. The aim of this study was to evaluate the efficacy and diagnostic performance of hybrid capture (HC) II and oligonucleotide microarray (HPV DNA chip) in detecting high risk HPV. Methods : Cytologic study, HC H, HPV DNA chip test and pathologic study (punch biopsy, cone biopsy or hysterectomy) were performed on 102 patients. The screening pe -formance was evaluated, such as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results : HPV tests were performed to detect high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68). The sensitivity of each test to detect low grade cervical intraepithelial neoplasia (LGCTN), high grade cervical intraepithelial neoplasia (HGCIN) and invasive cancer was 65.7% in HC H and 85.7% in oligonucleotide microarray. The combination of each test and cytologic study resulted in higher sensitivities, 90.0% in HC II and 95.5% in oligonucleotide. For patients with HGCIN and invasive cancer, the sensitivity was 71.7% in HC H and 86.8% in oligonucleotide microarray. In cases of multiple HPV subtype infection, the PPV of DNA chip was 89.5%. Conclusion : DNA chip test was more sensitive in detecting women with CIN lesion/invasive cancer and high risk HPV infection than HC H in a single test but no significant difference is found when combined with cytologic study. There was a highly significant correlation between multiple HPV subtype infection and CIN lesion/invasive cancer.

Infection with high-risk (HR) human papillomavirus (HPV) genotypes is an important risk factor for cervical cancers. We evaluated the clinical performances of two new real-time PCR assays for detecting HR HPVs compared to that of the Hybrid Capture 2 test (HC2). A total of 356 cervical swab specimens, which had been examined for cervical cytology, were assayed by Abbott RealTime HR and Roche Cobas HPV as well as HC2. Sensitivities and specificities of these assays were determined based on the criteria that concordant results among the three assays were regarded as true-positive or -negative and that the results of genotyping and sequencing were considered true findings when the HPV assays presented discrepant results. The overall concordance rate among the results for the three assays was 82.6%, and RealTime HR and Cobas HPV assays agreed with HC2 in 86.1% and 89.9% of cases, respectively. The two real-time PCR assays agreed with each other for 89.6% of the samples, and the concordance rate between them was equal to or greater than 98.0% for detecting HPV type 16 or 18. HC2 demonstrated a sensitivity of 96.6% with a specificity of 89.1% for detecting HR HPVs, while RealTime HR presented a sensitivity of 78.3% with a specificity of 99.2%. The sensitivity and specificity of Cobas HPV for detecting HR HPVs were 91.7% and 97.0%. The new real-time PCR assays exhibited lower sensitivities for detecting HR HPVs than that of HC2. Nevertheless, the newly introduced assays have an advantage of simultaneously identifying HPV types 16 and 18 from clinical samples.