In vitro study of HPV18-positive cervical cancer HeLa cells based on CRISPR/Cas13a system.

The E6 protein is a known oncogene in cervical cancer and plays a key role in the development and progression of cervical cancer by reducing the expression level of the tumor suppressor protein P53 and ultimately leading to enhanced cell proliferation and reduced apoptosis. Therefore, antiviral agents that inhibit the expression of E6 oncoprotein are expected to be potential therapies for human cervical cancer. Here we developed CRISPR/Cas13a: crRNA dual plasmid system and demonstrated that CRISPR/Cas13a could effectively and specifically knock down human papillomavirus 18 E6 mRNA, downregulate the expression level of E6 protein, and restore the expression of the tumor suppressor gene P53 protein, thereby inhibiting the growth of cervical cancer cells and increasing their apoptosis, the E6-2, E6-3, and E6-5 groups resulted in apoptosis rates of 25.4%, 22.4%, and 22.2% in HeLa cells. Moreover, CRISPR/Cas13a enhances the proliferation inhibition and apoptosis induction of cisplatin in cervical cancer HeLa cells. The CRISPR/Cas13a system targeting HPV E6 mRNA may be a promising therapeutic approach for the treatment of human papillomavirus-associated cervical cancer.

Interferon-γ-induced GBP1 is an inhibitor of human papillomavirus 18.

BACKGROUND: Human papillomavirus (HPV) infection is an important factor leading to cervical cell abnormalities. 90% of cervical cancers are closely associated with persistent infection of high-risk HPV, with the highest correlation with HPV16 and 18. Currently available vaccines and antivirals have limited effectiveness and coverage. Guanylate binding protein 1 (GBP1) was induced by interferon gamma and involved in many important cellular processes such as clearance of various microbial pathogens. However, whether GBP1 can inhibit human papillomavirus infection is unclear. RESULTS: In this study, we found that GBP1 can effectively degrade HPV18 E6, possibly through its GTPase activity or other pathways, and E6 protein degrades GBP1 through the ubiquitin-proteasome pathway to achieve immune escape. CONCLUSION: Therefore, GBP1 is an effector of IFN-γ anti-HPV activity. Our findings provided new insights into the treatment of HPV 18 infections.

Nona-Arginine Mediated Anti-E6 ShRNA Delivery Suppresses the Growth of Hela Cells in vitro.

Background: The E6 oncoprotein of HPV plays a crucial role in promoting cell proliferation and inhibiting apoptosis, leading to tumor growth. Non-viral vectors such as nona-arginine (R9) peptides have shown to be potential as carriers for therapeutic molecules. This study aimed to investigate the efficacy of nona-arginine in delivering E6 shRNA and suppressing the E6 gene of HeLa cells in vitro. Methods: HeLa cells carrying E6 gene were treated with a complex of nona-arginine and E6 shRNA. The complex was evaluated using gel retardation assay and FESEM microscopy. The optimal N/P ratio for R9 peptide to transfect HeLa cells with luciferase gene was determined. Relative real-time PCR was used to evaluate the efficiency of mRNA suppression efficiency for E6 shRNA, while the effect of E6 shRNA on cell viability was measured using an MTT assay. Results: The results indicated that R9 efficiently binds to shRNA and effectively transfects E6 shRNA complexes at N/P ratios greater than 30. Transfection with R9 and PEI complexes resulted in a significant toxicity compared to the scrambled plasmid, indicating selective toxicity for HeLa cells. Real-time PCR confirmed the reduction of E6 mRNA expression levels in the cells transfected with anti-E6 shRNA. Conclusion: The study suggests that R9 is a promising non-viral gene carrier for transfecting E6 shRNA in vitro, with significant transfection efficiency and minimal toxicity.

Human papillomavirus vaccination receipt and provider counseling rates among high-risk patients.

OBJECTIVE: We describe provider documented counseling patterns and perception regarding HPV vaccination among patients with a history of cervical dysplasia. METHODS: All patients ages 21-45 who underwent colposcopy at a single academic medical center from 2018 to 2020were sent a self-administered survey through the electronic medical record patient portal to assess their attitudes regarding human papillomavirus (HPV) vaccination. Demographic information, HPV vaccination history, and documented obstetrics and gynecology provider counseling at the time of colposcopy were examined. RESULTS: Of 1465patients, 434 (29.6 %) reported or had documented receipt of at least one dose of the human papillomavirus vaccine. The remainder reported they were not vaccinated or had no documentation of vaccination. Proportion of vaccinated patients was higher among White compared to Black and Asian patients (P = 0.02). On multivariate analysis, private insurance (aOR 2.2, 95 % CI 1.4-3.7) was associated with vaccinated status while Asian race (aOR 0.4, 95 % CI 0.2-0.7) and hypertension (aOR 0.2, 95 % CI 0.08-0.7) were less likely to be associated with vaccination status. Among patients with unvaccinated or unknown vaccination status, 112 (10.8 %) received documented counseling regardingcatch-up human papillomavirus vaccination at a gynecologic visit. Patients seen by a sub-specialist obstetrics and gynecologic provider were more likely to have documented provider counseling regarding vaccination compared to those seen by a generalist obstetric/gynecologist provider (26 % vs 9.8 %, p < 0.001). Patients cited lack of physician discussion (53.7 %) and the belief that they were too old to receive the HPV vaccine (48.8 %) as the main reasons for remaining unvaccinated. CONCLUSION: HPV vaccination and the rate of obstetric and gynecologic provider counseling regarding HPV vaccination among patients undergoing colposcopy remains low. When surveyed, many patients with a history of colposcopy cited provider recommendation as afactor in their decision to undergo adjuvant HPV vaccination, demonstrating the importance of provider counseling in thisgroup.

The association between high-risk human papillomavirus and oral lichen planus.

OBJECTIVES: Oral lichen planus (OLP) is a cell-mediated inflammatory mucosal disorder and is classified as an oral potentially malignant disorder. Some research has shown that apoptosis in OLP cells is similar to a viral infection such as human papillomavirus (HPV). So, the aim of this case-control study was to investigate the association of high-risk HPV with OLP. MATERIAL AND METHODS: DNA was extracted from 25 formalin-fixed, paraffin-embedded (FFPE) OLP tissues and 25 FFPE normal oral tissues as case and control groups, respectively. The presence of high-risk HPV16 and HPV18 DNA was investigated by polymerase chain reaction (PCR). p-value<.05 was considered significant. RESULTS: Twelve samples (48%) of OLPs were positive for HPV16, compared with six samples (24%) of controls; although the difference was not significant, it was borderline (p = .07). Three samples (12%) of OLPs were positive for HPV18 compared with one sample (4%) of controls; the difference was not significant (p = .3). The total frequency of both high-risk HPV were 14 samples (56%) of OLPs and 7 samples (28%) of controls; there was a significant association between the high-risk HPV and OLP (p = .04). High-risk HPVs was more prevalent in erosive-atrophic (EA) form of OLP as compared to non-EA form, although the difference was not significant (p = .13). CONCLUSIONS: The results suggest a significant association between high-risk HPVs and OLP.

PCR-based Evaluation of Human Papillomavirus Genotypes in Oral Lichen Planus.

Objective: The objective of the study was to use polymerase chain reaction (PCR) to examine and compare the genotype distribution of human papillomavirus (HPV) in oral lichen planus (OLP). Materials and Methods: Deoxyribonucleic acid (DNA) was extracted from 20 OLP biopsy specimens. Conventional PCR assay employing consensus HPV primers was used to identify HPV DNA. Positive PCR samples were then subjected to PCR assay with HPV type-specific primers. Results: Out of the total 20 OLP specimens evaluated, eight samples (40%) were positive for HPV. Females had a 41.7% higher HPV-positive rate than males. The most common type in the HPV type-specific PCR assay was HPV-18 (75%), which is a high-risk type of HPV linked to malignant diseases. The erosive kind of OLP had the greatest percentage of HPV positives (50%). Conclusion: The present study confirms the detection of HPV in OLP lesions, as determined by PCR-coupled HPV gene sequencing, as well as its likely mechanism of malignant transformation.

Searching for the methylation sites involved in human papillomavirus type 16 and 18­positive women with cervical cancer.

It has been reported that >90% of women with cervical cancer are human papillomavirus (HPV)-positive, with HPV16 and 18 being the most 'highest-risk' HPV genotypes. However, in numerous women, HPV infection will not progress to cervical cancer. Accordingly, more appropriate screening markers need to be explored. In the present study, genome-wide DNA methylomic differences between cervical cancer tissues with HPV-16 or HPV-18 infection and normal cervical tissues were detected by using an Illumina Human Methylation 850 K BeadChip. The Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted in order to define the nearest neighbouring genes of differentiated methylation sites. Moreover, differentiated methylation sites were verified using pyrosequencing. KEGG analyses suggested that the focal adhesion pathway and pathways in cancer were highly enriched. Bioinformatics and statistical analysis indicated that the nine CpG loci had the most significant differences amongst the genes involved in these pathways. Among these, six CpG sites in the CHRM2, LAMA4, COL11A1, FGF10, IGF1 and TEK genes were highly associated with HPV-16-positive cervical cancer, as validated using pyrophosphate sequencing. Additionally, 10 significantly different CpG sites of the HPV-18-positive group were selected and verified in The Cancer Genome Atlas, indicating their possible diagnostic roles in cervical cancer development and determination. In addition, eight hypermethylated CpG island sites that were associated with HPV-16-positive cervical cancer tissues and 10 hypermethylated CpG island sites that were associated with HPV-18-positive cervical cancer tissues were identified, highlighting their potential roles in screening and evaluating targeted therapy efficacy and prognosis. The main focus of the present study was to identify the genetic variability in HPV-16- and HPV-18-positive samples and to elucidate possible methylation biomarkers in HPV-positive women with a risk of developing cervical cancer.

Repositioning of Anti-Inflammatory Drugs for the Treatment of Cervical Cancer Sub-Types.

Cervical cancer is the fourth most commonly diagnosed cancer worldwide and, in almost all cases is caused by infection with highly oncogenic Human Papillomaviruses (HPVs). On the other hand, inflammation is one of the hallmarks of cancer research. Here, we focused on inflammatory proteins that classify cervical cancer patients by considering individual differences between cancer patients in contrast to conventional treatments. We repurposed anti-inflammatory drugs for therapy of HPV-16 and HPV-18 infected groups, separately. In this study, we employed systems biology approaches to unveil the diagnostic and treatment options from a precision medicine perspective by delineating differential inflammation-associated biomarkers associated with carcinogenesis for both subtypes. We performed a meta-analysis of cervical cancer-associated transcriptomic datasets considering subtype differences of samples and identified the differentially expressed genes (DEGs). Using gene signature reversal on HPV-16 and HPV-18, we performed both signature- and network-based drug reversal to identify anti-inflammatory drug candidates against inflammation-associated nodes. The anti-inflammatory drug candidates were evaluated using molecular docking to determine the potential of physical interactions between the anti-inflammatory drug and inflammation-associated nodes as drug targets. We proposed 4 novels anti-inflammatory drugs (AS-601245, betamethasone, narciclasin, and methylprednisolone) for the treatment of HPV-16, 3 novel drugs for the treatment of HPV-18 (daphnetin, phenylbutazone, and tiaprofenoic acid), and 5 novel drugs (aldosterone, BMS-345541, etodolac, hydrocortisone, and prednisolone) for the treatment of both subtypes. We proposed anti-inflammatory drug candidates that have the potential to be therapeutic agents for the prevention and/or treatment of cervical cancer.

HPV vaccination among seropositive, DNA negative cohorts: a systematic review & meta-analysis.

OBJECTIVE: Vaccine efficacy among previously exposed, but currently uninfected women, i.e., those who have serological evidence of a prior human papillomavirus (HPV) infection without corresponding detectable HPV DNA, remains incompletely defined. This meta-analysis assessed the serotype-specific efficacy of prophylactic HPV vaccination against HPV16/18 persistent infection (PI) and cervical intraepithelial neoplasia (CIN) among seropositive, DNA negative (SPDN) women enrolled to randomized controlled trials (RCTs) of HPV L1-based vaccines. METHODS: Searches were conducted on 08/16/20 on MEDLINE, Embase, Scopus and CENTRAL. RCTs of L1-based prophylactic bivalent or quadrivalent HPV vaccines, reporting serotype-specific clinical efficacy endpoints in the HPV16/18 seropositive, DNA-negative populations were included. Relative risks (RRs) of 6-month PI (6mPI), 12-month PI (12mPI), CIN1+ and CIN2+ were pooled using a random-effects model. RESULTS: A total of 1,727 citations were reviewed. 8 studies, with a total of 9,569 SPDN participants, met all eligibility criteria. The RR of 6mPI (RR=0.22; 95% confidence interval [CI]=0.08-0.61; p=0.018), 12mPI (RR=0.20; 95% CI=0.05-0.80; p=0.035), CIN1+ (RR=0.13; 95% CI=0.05-0.30; p=0.003) and CIN2+ (RR=0.15; 95% CI=0.04-0.59; p=0.022) was significantly reduced in the vaccinated compared to the unvaccinated group. CONCLUSION: Our findings suggest high serotype-specific efficacy for HPV vaccination among cohorts of women with evidence of prior HPV16/18 infections, including 87% efficacy (95% CI=70%-95%; p=0.003) against HPV16/18 cervical dysplasia. HPV vaccination is highly effective among uninfected women, regardless of prior exposure history. TRIAL REGISTRATION: PROSPERO Identifier: CRD42020206888.

Observation on the composition and distribution of human papillomavirus infection and its aging changes in female genital tract of Zhuang and Han nationality in Guangxi / 中华老年医学杂志

Objective:To study the composition and distribution of human papillomavirus(HPV)in female genital tract of Zhuang and Han nationality in Guangxi.Methods:The composition and distribution of cervical human papillomavirus(HPV)infection in Han and Zhuang women visiting Department of Gynecology and Obstetrics of the First Affiliated Hospital of Guangxi Medical University from August 2012 to October 2020 were retrospectively analyzed to provide the basic data for prevention and treatment of HPV infection.A total of 20 736 cases were divided into Han nationality group(n=16 390 cases)and Zhuang nationality group(n=4 346 cases). Polymerase chain reaction(PCR)was used to detect HPV type 21 and analyze the epidemiological characteristics of cervical HPV in women of different ethnic groups in this area.Results:In the 20, 736 cases, the proportion of positive HPV was 27.0%(5 591/20, 736). Among them, positive HPV accounted for 27.7%(4 536)in the Han group, and 24.3%(1 055)in Zhuang group, which were statistically significant( χ2=20.17, P<0.01). Peak age of infection in Zhuang women was more than 65 years.The most common HPV genotypes in both ethnics groups in Guangxi were HPV 16, 52, 58, 18, and 53.In women with positive HPV, the constituent ratio of HPV16 and HPV 52 rose with age ageing, while constituent ratio of HPV 6 and 11 presented the opposite trend. Conclusions:The HPV and HR(high-risk)-HPV positive composition ratio is lower in Zhuang women than in Han women in Guangxi.Among Han and Zhuang females, HPV 16, 52, 58, 18 and 53 have the highest positive composition ratio.HPV genotyping shows an age-increasing change.

Prevalence of Human Papillomavirus (HPV) 16 and 18 in Oral Malignant and Potentially Malignant Disorders: A Polymerase Chain Reaction Analysis - A Comparative Study.

INTRODUCTION: Human papillomavirus (HPV) are now being increasingly associated as a cause of oral squamous cell carcinomas (OSCC). This study was designed to evaluate the prevalence of HPV in Pelizaeus-Merzbacher disease (PMD) and OSCC using polymerase chain reaction that might help in better understanding of the role played by this virus in the oncogenic process even from its evolution stage. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue samples (n = 40) of OSCC and mild, moderate, and severe dysplasia were used for this study. DNA was quantified and checked for purity spectrophotometrically. Statistical analysis was performed using SPSS software and statistical significance was assessed using Fischer's exact test (p < 0.05 was considered significant). RESULTS: High-risk (HR)-HPV-16 was found to be positive in 35% of OSCC cases which showed a statistically significant association of HPV 16 with OSCC. Verrucous carcinoma had predominant HPV 16 infection (60%), followed by SCC with 40%. However, this association was not statistically significant. None of the OSCC samples were infected with HPV 18. Among the PMD, we found only 5% showing HR-HPV 16 infection which was not significant. DISCUSSION: Although OSCC is attributed to tobacco and alcohol consumption, a significant proportion of OSCC cases have been demonstrated to contain HPV types. The high-risk HPV type 16 tends to be the most predominant type detected in cases of OSCC.

HPV infections in retinoblastoma: a systematic review.

BACKGROUND: Retinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%-5% of all childhood cancers. Recent studies demonstrated that interacting between RB tumor suppressor and oncoproteins of DNA tumor viruses such as human papillomavirus (HPV). The objective of the current systematic review study was to present conducted studies in the field of HPV infection and its possible role in retinoblastoma. METHODS: For this systematic review, all relevant original research studies were assessed by searching in electronic databases include PubMed, Embase, Scopus, Google Scholar, and Web of Science by using relevant keywords. The study was designed based on the PRISMA criteria. All publications with English literature and original researches are considered for screening. RESULTS: Conducted search results lead to 4070 studies. The title and abstract screening lead to 11 studies. Data extraction was performed on 8 included studies. The prevalence of the HPV was ranged from 0 to 69%, and HPV genotype 16 and 18 were the most detected types. The most used method for the detection of the viruses was PCR, and the most assessed sample was formalin-fixed, paraffin-embedded tissue blocks. CONCLUSION: The association between HPV and retinoblastoma is still inconsistent. The prevalence of the HPV in RB was ranged from 0 to 69%, which indicates a wide range and highlights the importance of further investigation for more accurate statistical of HPV prevalence in RB. Thus, further worldwide studies of larger sample sizes of cohorts should be investigated to clarify this uncertainty.

Human Papilloma Virus 18-Positive Submucosal Small Cell Neuroendocrine Carcinoma of the Vagina: An Immunohistochemical and Genomic Study.

Primary vaginal neuroendocrine carcinoma (NEC) is extremely rare among female genital tract tumors. Here, we report 2 cases of vaginal small cell NEC (SCNEC) using immunohistochemistry and next-generation sequencing (NGS) analysis. The 2 patients were in their mid-to-late 70s, presented with abnormal vaginal bleeding and had a vaginal submucosal mass. The biopsied or resected tumors showed a typical neuroendocrine morphology consisting of solid nests of atypical tumor cells, with no specific organoid patterns, and proliferating in the vaginal submucosa. Immunohistochemical analysis showed strong and diffuse expression of chromogranin A, synaptophysin, and p16, but no thyroid transcription factor 1 expression. Additionally, both cases were positive for human papillomavirus (HPV) 18. An NGS-based cancer panel analysis revealed that the tumors carried NF1 and AR mutations, but no major driver mutations were detected. The results of this study suggested that HPV18 infection is linked to vaginal SCNEC.

Expression of Sp100 Protein in Human Papillomavirus-Associated Sinonasal Inverted Papilloma.

OBJECTIVE: Sinonasal inverted papilloma (SNIP) is a benign tumor characterized by an aggressive growth, a tendency to recur, and an association with malignancy. However, the precise etiology of SNIP is still unknown. The objective of this study was to identify the expression pattern of speckled protein 100 (Sp100) in the malignant transformation (MT) of SNIP and its correlation with human papillomavirus (HPV)-16 and HPV-18 infections and other clinical features. This would further help in understanding the possible mechanisms for the development of SNIP. METHODS: Individual nasal mucosa specimens from 40 patients (25 males and 15 females) and 10 inferior turbinate specimens as controls were included in the present study. The samples were divided into several sections for histopathological examination, HPV DNA detection, and immunohistochemical staining. RESULTS: We observed that as SNIP progressed, the Sp100 protein expression was gradually downregulated, and SP100 localization changed from nucleus to the cytoplasm. Positive rate of HPV infection in the SNIP with MT group was higher than that in the other groups, and Sp100 expression was correlated to HPV infections and SNIP with MT. However, no correlation was observed between Sp100 expression and clinical features, such as age, gender, and smoking. CONCLUSION: Positive rate of HPV infection is high in the SNIP with MT and has a correlation with Sp100 expression. In addition, the expression of Sp100 is downregulated in SNIP with MT, and Sp100 may play a role in the progression of SNIP.

The utility of high-risk human papillomavirus E6/E7 mRNA in situ hybridization in assessing HPV status on cell block.

INTRODUCTION: Assessment of human papillomavirus (HPV) status is critical to the treatment and prognosis of patients with oropharyngeal squamous cell carcinoma. Patients often present with enlarged cervical lymph nodes which are amenable to fine needle aspiration (FNA) and cell block creation. The most widely used method for assessing HPV status is the surrogate marker p16. Other HPV specific methods such as high-risk HPV E6/E7 mRNA in situ hybridization (ISH) have been shown to perform as well as p16 and are easier to interpret. Our study evaluates the utility of high-risk HPV mRNA ISH in cell block specimens. METHODS: Thirty-six cases of metastatic squamous cell carcinoma in cervical neck lymph node FNAs were identified over a 3-year period. All cases had p16 immunohistochemistry (IHC) performed on cell block. HR HPV mRNA ISH was performed on the cell block and compared to the p16 results. Additionally, p16 and HR HPV mRNA ISH status was assessed in those cases with corresponding surgical resections. RESULTS: HR HPV mRNA ISH confirmed the p16 IHC (either positive or negative) in 24 of the 36 cases (66.7%). Six false negative cases were p16 negative/HR HPV mRNA ISH positive. HR HPV mRNA ISH was positive in 75% of the four p16 equivocal cases. Two cases were p16 positive/HR HPV mRNA ISH negative. CONCLUSIONS: HR HPV mRNA ISH is no more difficult to perform in the IHC lab and is easier to interpret than p16 IHC. HR HPV mRNA ISH is a useful alternative to p16 in cell block specimens.

Human papillomavirus genotype distribution in head and neck cancer: Informing developing strategies for cancer prevention, diagnosis, treatment and surveillance.

Current clinical practice algorithms for HPV testing make no effort to discern the impact of genotypes for patients with head and neck squamous cell carcinoma (HNSC). Data was collected for all patients with HNSCs that had undergone HPV testing at an academic hospital as part of clinical care (2012-2019). Screening was performed using real-time PCR targeting L1 of low and high-risk HPV types, followed by genotyping of positive cases. Genotype status was correlated with age, site and histologic parameters. Of the 964 patients tested, 68% had HPV-positive cancers. Most arose from the oropharynx (OP) (89%) and sinonasal tract (5%). The most frequent genotype was 16 (84.4%) followed by 35 (5.6%), 33 (4.1%), 18 (2.7%), 45 (1.1%), 69 (0.8%) and others (1.3%). There was an association between genotype (16 vs non-16) and tumor origin (OP vs non-OP) (p < 0.0001). HPV18 was associated with transformation to an aggressive small cell phenotype, but HPV16 was not (22% vs 0%, p < 0.0001). Patients with HPV-non-16 OP carcinomas were older than patients with HPV16 OP carcinomas, but the difference was not significant. HPV genotypes are variable and unevenly distributed across anatomic sites of the head and neck. The association of HPV18 with small cell transformation suggests that variants can track with certain phenotypes in ways that may account for differences in clinical behavior. This study challenges the prevailing assumption of HPV equivalency across all high-risk genotypes in ways that may inform preventive, diagnostic, therapeutic and surveillance strategies.

Prognostic implication of human papillomavirus types in cervical cancer patients: a systematic review and meta-analysis.

BACKGROUND: To estimate the prognostic relevance of human papillomavirus (HPV) 16 and HPV 18 in patients with cervical cancer. METHOD: We searched PubMed, EMBASE, American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO), CNKI, and Wanfang databases to search primary articles illustrating the survival outcomes in cervical cancer patients with or without HPV 16/18 infection. A meta-analysis was conducted to generate a combined hazard ratio (HR) with 95% confidence intervals (CI) for progression-free survival (PFS), disease free survival (DFS) and overall survival (OS). RESULTS: A total of 13 studies were included. Our meta-analysis revealed that HPV 16 positive did not have any impact on OS (HR, 0.76; 95% CI = 0.37-1.54; P = 0.44). Cervical cancer patiensts infected with HPV 18 had worse OS (HR, 1.66; 95% CI = 1.28-2.17; P = 0.0001), DFS (HR, 2.10; 95% CI = 1.73-2.54; P < 0.0001) and worse PFS (HR, 2.97; 95% CI = 1.69-5.23; P = 0.00012) compared with those not infected with HPV 18. cervical cancer patiensts infected with HPV 18 had worse PFS compared with those infected with HPV 16 ((HR, 1.34; 95% CI = 1.06-1.70; P = 0.01). CONCLUSION: Cervical cancer patients infected with HPV 18 had worse survival compared with cervical cancer patients with HPV 16 infection.

Better or Worse? The Independent Prognostic Role of HPV-16 or HPV-18 Positivity in Patients With Cervical Cancer: A Meta-Analysis and Systematic Review.

Background: The literature reports conflicting results regarding the effect of human papillomavirus (HPV) genotype 16 (HPV-16)/18 (HPV-18) positivity on cervical cancer (CC) prognosis. Aim: To conduct a meta-analysis to examine the effect of HPV-16/18 positivity on the prognosis of patients with CC. Methods: PubMed, Embase, and the Cochrane Library were searched for available papers published up to March 2020. The main outcome was the hazard ratio (HR) of overall survival (OS) or disease-free survival (DFS) comparing HPV-16 or HPV-18 positivity and negativity. The random-effects model was used for synthesizing survival outcomes. Results: Nine studies and 2,028 patients were included. Four studies reported OS in HPV-16 positivity, and no association was found between HPV-16 positivity and OS to CC (HR = 0.79, 95% CI: 0.26-2.39, P = 0.675). Three studies reported DFS in HPV-16 positivity, and no association was found between HPV-16 positivity and DFS to CC (HR = 0.80, 95% CI: 0.30-2.11, P = 0.654). Two studies reported DFS in HPV-18 positivity, and no association was found between HPV-18 positivity and DFS to CC (HR = 0.99, 95% CI: 0.55-1.78, P = 0.984). One study reported progression-free survival (PFS) in HPV-18 positivity, and an association was observed between HPV-18 positivity and PFS to CC (HR = 2.66, 95% CI: 1.44-4.94, P = 0.002). The sensitivity analyses showed that one study biased the analysis of the association between HPV-16 and OS, and another study biased the association between HPV-16 and DFS. Conclusion: The presence of HPV-16 and HPV-18 positivity appears to have no significant association with prognosis in CC in either OS or PFS. The presence of HPV-16 or HPV-18 positivity has no significant association with prognosis in CC in either OS or PFS.

[Evaluation of the effectiveness of BMRT-HPV for cervical cancer screening].

Objective: Evaluation of the clinical value of the BioPerfectus multiplex real time (BMRT)-HPV for cervical cancer screening. Methods: Physician-collected specimens of 1 495 women who were positive of Cobas 4800 HPV (Cobas-HPV), HPV genotyping based on SEQ uencing (SEQ-HPV), and (or) cytology ≥low grade squamous intraepithelial lesion (LSIL) in the primary screening of Chinese Multiple-center Screening Trial (CHIMUST), and 2 990 women selected from those who were negative of primary screening in the same project through nested control randomization with age-matching were tested for BMRT-HPV, which reported type-specific viral loads/10 000 cells in each specimen. With comparing to Cobas-HPV results and taking cervical histopathological diagnosis as the endpoint, the concordance of high-risk (HR)-HPV subtypes among the three assays was explored ,and the sensitivity and specificity of BMRT-HPV for cervical cancer screening were evaluated. Results: (1) The overall agreenment of HR-HPV subtypes between BMRT-HPV and Cobas-HPV, or SEQ-HPV test sample was 94.8%, 94.4%, with Kappa values 0.827, 0.814. (2) The sensitivity and specificity for cervical intraepithelial neoplasia (CIN) Ⅱ+ of BMRT-HPV, Cobas-HPV and SEQ-HPV were 92.62%, 94.26%, 93.44% and 84.67%, 83.25%, 82.76%, respectively. There were no significant difference in sensitivity among the three HPV assays (all P>0.05), but the specificity of BMRT-HPV for CIN Ⅱ+ was higher than those of Cobas-HPV and SEQ-HPV (P<0.01). The sensitivity for CIN Ⅲ+ of three HPV assays were all 100.00%, and the specificity for CIN Ⅲ+ of BMRT-HPV was higher than those of Cobas-HPV and SEQ-HPV (83.40% vs 81.95%, 83.40% vs 81.50%; P<0.01). The number of pathological examinations of colposcopy for cervical biopsy detected in 1 case of CIN Ⅱ+ or CIN Ⅲ+ in BMRT-HPV was less than those in Cobas-HPV and SEQ-HPV (P<0.01). When using HPV 16/18 + cytology ≥atypical squamous cell of undetermined signification (ASCUS) to triage HPV positive women among three assays, there was no different in the sensitivities of detecting CIN Ⅱ+ and CIN Ⅲ+ (P>0.05). The specificity BMRT-HPV was slightly higher than those in Cobas-HPV or SEQ-HPV (all P<0.05), and the colposcopy referral rate was lower than those in Cobas-HPV and SEQ-HPV (all P<0.05). Conclusions: BMRT-HPV is as sensitive as Cobas-HPV or SEQ-HPV for primary cervical cancer screening, and has higher specificity. Therefore it could be used as a primary screening method for cervical cancer, which is worthy of clinical application.

Frequency of high-risk genotypes of human papilloma virus in oral lesions / Frecuencia de genotipos alto riesgo del virus papiloma humano en lesiones bucales

Some genotypes of the human papilloma virus (HPV) in the oral cavity cause genetic instability that may lead to cancer. Clinical and histological diagnoses are key tools; however, molecular techniques allow predicting, detecting and monitoring the disease. Objective: To identify the frequency of four high-risk HPV genotypes and their association with lesions in the oral cavity. Materials and Methods: Descriptive cross-sectional study with a sample of 48 patients diagnosed with hyperplastic lesions and others currently classified as potentially malignant disorders (PMDs) of the oral cavity, who underwent biopsies, histopathological analysis, and HPV16, 18, 31, and 45 detection and genotyping by polymerase chain reaction (PCR). Results: Epithelial hyperplasia was the most frequent lesion found in 45.8% (n=22) of patients. Nicotine palatinus and leukoplakia were found in 8.3% and 6.2%, respectively; oral cancer in 6.2%. The total frequency of HPV was 12.5% (6/48). Oral papilloma was found in 6.1% (3/48), and nicotine palatinus and oral cancer in 2.0% each (1/48). HPV16, HPV31, and HPV45 were detected, while HPV18 was not observed. HPV16 was the most frequent genotype found (4 out of 6 patients), while HPV31 and HPV45 were found in one patient each. Only one genotype per lesion was found. The presence of HPV was associated with lesions (χ2=11.810; p=0.0375). No significant association with age and gender was found. Conclusion: High-risk HPV continues to be present in oral lesions. The HPV16 viral genotype was the most frequent in the studied lesions.

Algunos genotipos del virus del papiloma (VPH) en boca, producen inestabilidad genética dando lugar al cáncer. El diagnóstico clínico e histológico son herramientas claves, sin embargo, técnicas moleculares permiten predecir, detectar y dar seguimiento a la enfermedad. Objetivo: Identificar la frecuencia de cuatro genotipos del VPH de alto riesgo y su asociación con lesiones en cavidad bucal. Material y Métodos: Estudio descriptivo de corte transversal con una muestra de 48 pacientes diagnosticados con lesiones hiperplásicas y otros clasificados actualmente como desordenes potencialmente malignos (DPM) de la cavidad bucal, a quienes se les realizó biopsias, análisis histopatológico y detección y genotipificación VPH16, 18, 31, y 45 mediante reacción en cadena a la polimerasa (PCR). Resultado: La hiperplasia epitelial fue la lesión más frecuente en 45,8% (n=22). La palatinitis nicotínica y la leucoplasia, se encontraron 8,3% y 6,2% respectivamente, cáncer oral, en 6,2%. La frecuencia total de VPH fue 12,5% (6/48). El papiloma oral estuvo en un 6,1% (3/48), palatinitis nicotínica y cáncer oral en 2,0% (1/48).Se detectó VPH16, VPH31 y VPH45, mientras que VPH18 estuvo ausente. ElVPH16 fue el de mayor frecuencia con 66,7% (4/6), el VPH31 y VPH45 se encontraron en 16,7% (1/6). No se evidenció más de un genotipo por lesión. La presencia de VPH estuvo asociado con las lesiones (χ2=11,810; p=0,0375). No se encontró asociación significativa con edad y género. Conclusión: El VPH de alto riesgo sigue estando presente en lesiones bucales. El genotipo viral VPH16 se encontró con mayor frecuencia en las lesiones estudiadas.