HPV-negative Group Research Articles

Analyses of human papillomavirus, Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, and co-infections in a gynecology outpatient clinic in Haikou area, China

BackgroundThe purpose of this study was to study the infection rates of Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Neisseria gonorrhoeae (NG), and co-infections with human papillomavirus (HPV) in a hospital gynecology outpatient clinic in the Haikou region in 2021.MethodsFrom January to December 2021, the Women and Children Medical Center of Hainan Province collected 2389 samples of cervical exfoliated cells and vaginal swab specimens from gynecologic outpatients. The samples were then analyzed descriptively for data, and the detection rate of each pathogen was tallied. All vaginal swabs were obtained for CT, UU, and NG DNA testing, and cervical exfoliated cells for HPV genotyping. Analyses were performed on the detection rate of each group.ResultsIn 2389 samples, the frequencies of pathogen identification among the 2389 samples were as follows: UU (58.43%); HPV (17.29%); CT (7.99%); and NG (0.38%). HPV, CT, UU, and NG were detected in 33.33%, 22.55%, 77.45%, and 2.94% of individuals between 15 and 20 years of age, respectively. The detection rates of CT, UU, and NG were substantially greater in the HPV-positive group than the the HPV-negative group (P < 0.05).ConclusionAmong gynecologic outpatients at a hospital in the Haikou area, the probability of mixed infections with genital tract pathogens in HPV-positive patients was higher compared to HPV-negative patients. Reproductive tract infections are becoming more prevalent in younger people, hence adolescent sexual health education needs improvement.

Impact of an HPV diagnosis on the psychosexual sphere

We aimed to evaluate the psychosexual impact of being diagnosed with human papillomavirus (HPV). A cross-sectional study was conducted to assess the anxiety and depression levels and sexual functions in women with and without HPV between March and May 2021. Beck anxiety inventory (BAI), the Beck depression inventory (BDI), and the Libido scoring system scales (LSSS) were used as scales. A total of 575 respondents were included; 292 (50.2%) HPV-negative, and 283 (49.8%) HPV-positive, of whom 170 (60,1%) had high risk HPV genotypes 16/18 and 113 (39,9%) had non-16/18 high risk HPV-positive patients. There was no significant association between HPV-negative and HPV-positive patients in terms of sociodemographic characteristics. While 21.6% of the HPV-positive group experienced masturbation, it was 15.1% in the HPV-negative group (p=0.044). While severe depression was 4.9% in HPV-positive women, this rate was 1.4% in HPV-negative women (p=0.002). The present study showed that being diagnosed with HPV made a significant difference in sexual function, except for sexual interest, but increased anxiety and depression scores. Sexual dysfunction following an HPV diagnosis cannot be explained solely by depression and anxiety.

Association between human papillomavirus infection and common sexually transmitted infections, and the clinical significance of different Mycoplasma subtypes.

Human papillomavirus (HPV) infection, especially persistent high-risk HPV, is associated with cervical cancer. Female reproductive tract microecological disorders and lower genital tract infections have been increasingly correlated with HPV infection and cervical lesions. Due to their common risk factors and transmission routes, coinfection with other sexually transmitted infections (STIs) has become a concern. Additionally, the clinical significance of Mycoplasma subtypes appear to vary. This study aimed to assess the correlations between common STIs and HPV infection, and to investigate the clinical significance of Mycoplasma subtypes. We recruited 1,175 patients undergoing cervical cancer screening at the Peking University First Hospital gynecological clinic from March 2021 to February 2022 for vaginitis and cervicitis tests. They all received HPV genotyping and detection of STIs, and 749 of them underwent colposcopy and cervical biopsy. Aerobic vaginitis/desquamative inflammatory vaginitis and STIs (mainly single STIs) were found significantly more often in the HPV-positive group than in the HPV-negative group. Among patients with a single STI, rates of infection with herpes simplex virus type 2 or UP6 in the HPV-positive group were significantly higher than in the HPV-negative group (ORadj: 1.810, 95%CI: 1.211-2.705, P=0.004; ORadj: 11.032, 95%CI: 1.465-83.056, P=0.020, respectively). Through detailed Mycoplasma typing, a correlation was found between different Mycoplasma subtypes and HPV infection. These findings suggest that greater attention should be paid to detecting vaginal microecological disorders in those who are HPV-positive. Further, lower genital tract infections, including both vaginal infections and cervical STIs, are significantly more common among women who are HPV-positive and who thus require more thorough testing. Detailed typing and targeted treatment of Mycoplasma should become more routine in clinical practice.

Clinical correlation analysis of HPV infection in adult laryngeal papilloma and adverse events

ObjectTo explore the factors affecting dysplasia and carcinogenesis in adult patients with laryngeal papilloma, and the clinical differences between human papillomavirus (HPV)-positive and HPV-negative patients. MethodsClinical data of 80 adult patients with laryngeal papilloma and associated adverse events were collected retrospectively. They had undergone surgery in the Department of Otolaryngology Head and Neck, Beijing Tongren Hospital, Capital Medical University between January 2010 and December 2020. HPV infection was detected using RNA in situ hybridization. ResultsRegression analysis showed that multiple lesions and high Ki-67 expression were independent factors affecting the occurrence of adverse events. Differences between the HPV-positive and HPV-negative groups were compared. The age and Ki-67 expression in the HPV-negative group were significantly higher than those in the HPV-positive group. In the severe dysplasia to carcinogenesis subgroup, the proportion of HPV-negative patients was significantly higher than that in the mild to moderate dysplasia subgroup. There was a high correlation between positive p16 immunohistochemistry (IHC) and positive HPV. ConclusionsMultiple lesions and high Ki-67 expression are independent factors that are linked with adverse laryngeal papilloma progression. Elderly HPV-negative patients are at an increased risk of severe dysplasia and carcinogenesis. Positive p16 IHC was very accurate in detecting HPV infection.

Relationship between vaginal microecological changes and oncogene E6/E7 and high-risk human papillomavirus infection

High-risk (HR)-human papillomavirus (HPV) is the leading cause of precancerous cervical lesions in patients with chronic untreated infection. We investigated the relationships among several vaginal microbiological alterations, oncogene E6/E7 expression, and HR-HPV. A total of 1327 women who underwent HPV screening, vaginal microecology determination, and fluid-based thin-layer cytological test were enrolled and classified into the HPV-negative group, the low-risk (LR)-HPV-positive group, and the HR-HPV-positive group. The status of cervical HPV infection, vaginal microecology, and E6/E7 mRNA expression were examined sequentially. The effect of HR-HPV infection on cervical cancer (CC) was meticulously assessed, and associations between HR-HPV infection and vaginal microecology and E6/E7 mRNA were identified. In total 548/1327 patients were HPV positive, including LR-HPV infection (N = 132) and HR-HPV infection (N = 416). Patients in the HR-HPV positive group revealed higher detection rates of bacterial vaginosis (BV), trichomonal vaginitis (TV), and vulvovaginal candidiasis (VVC) relative to the HPV negative group. A higher E6/E7 mRNA expression was identified in HR-HPV patients compared to LR-HPV patients. BV and E6/E7 mRNA were classified as independent risk factors for HR-HPV infection. Patients with HR-HPV infection were more susceptible to CC development. Overall, BV and E6/E7 mRNA expression were identified as independent risk factors for HR-HPV infection. IMPACT STATEMENT What is already known on this subject? Through literature review, we found that vaginal ecological changes increase the risk of HPV infection, and HPV persistent infection is an important risk factor for cervical precancerous lesions and cervical cancer. In addition, HPV gene E6/E7 is expressed in HPV-positive cervical cancer cells, which is related to cell malignant transformation and even tumorigenesis. What do the results of this study add? This study further revealed that bacterial vaginosis (BV) and E6/E7 mRNA were independently correlated with HR-HPV infection, and HR-HPV infection increased the risk of cervical cancer. What are the implications of these findings for clinical practice and/or further research? E6/E7 mRNA detection may be used as a new auxiliary diagnostic index for HR-HPV infection. In addition, this study provides a reference for whether the restoration of vaginal microecological balance in patients with BV undergoing clinical treatment is conducive to HR-HPV regression, and provides theoretical support for the prevention and control of cervical cancer microecological approach and the occurrence and development of cervical cancer.

Analysis of T1-T2 stage oropharyngeal squamous cell carcinoma treated with transoral robotic surgery.

Transoral robotic surgery (TORS) has become an effective treatment for early-stage oropharyngeal squamous cell carcinomas (OPSCCs). We aimed to analyze the clinical safety and efficacy of TORS for human papilloma virus (HPV)-positive and HPV-negative OPSCC in China. Patients with OPSCC of pT1-T2 stage who underwent TORS from March 2017 to December 2021 were analyzed. A total of 83 patients (HPV-positive, n=25; HPV-negative, n=58) were included. The median age of the patients was 57.0 years and 71 were men. The majority of primary tumor sites were palatine tonsils (52, 62.7%) and base of tongues (20, 24.1%). Three patients have a positive margin. A total of 12 (14.5%) patients received tracheotomies, the average duration of tracheostomy tube use was 9.4 days, and nasogastric tube was 14.5 days. No patient had a long-term tracheotomy. The 3-year overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) for all 83 patients were 89.5%, 80.1%, and 83.3%, respectively. The OS at 3 years between the HPV-positive group and HPV-negative group were 100% versus 84.3% (P=.07), while the DFS and RFS between two groups also showed no significant difference. Among multivariate cox regression analysis of all potential risk factors, smoking was the significant risk factors for disease recurrence (P< .05). Transoral robotic surgery achieved encouraging oncologic outcomes and safety in T1-T2 stage OPSCC treatment, regardless of HPV status. 4.

Microbiota unbalance in relation to high-risk human papillomavirus cervical infection

ObjectivesTo assess vaginal dysfunction using basic vaginal states and the presence of lactobacillary microbiota in patients with human papillomavirus (HPV) infection with no squamous intra-epithelial lesions (SIL), with low-grade squamous...

Role of Genetic Ancestry in Oropharyngeal Squamous-Cell Carcinoma: A Cross-Sectional Study in Brazil

Background: HPV infection represents an important etiologic factor for Oropharyngeal Squamous Cell Carcinoma (OPSCC). The different ethnic backgrounds could be related to different susceptibility to Human Papillomavirus (HPV). The aim of our study was to assess the whole of genetic ancestry in HPV status in OPSCC patients. Methods: We conducted a cross-sectional study on patients with OPSCC admitted to the Barretos Cancer Hospital, Brazil from 2014 to 2019. Of these, DNA extraction was performed on 40 patients and genetic ancestry was assessed using a specific panel of 46 informative ancestry markers. Results: We observed a predominance of European ancestry (63%), followed by African (18%), Amerindian (9%) and Asian (8%) both in the OPSCC HPV-positive and HPV-negative group. We did not find any statistically significant differences between the HPV-positive and HPV-negative OPSCC groups in relation to European (p = 0.499), African (p = 0.448), Asian (p = 0.275) or Amerindian (p = 0.836) ancestry. Conclusions: We found a predominance of European ancestry, both in the HPV-positive and HPV-negative groups. In our study, we did not find statistically significant differences between HPV-positive or HPV-negative groups in relation to ancestry.

Research of cervical microbiota alterations with human papillomavirus infection status and women age in Sanmenxia area of China.

BackgroundHuman papillomavirus (HPV) infection is the leading cause of cervical cancer. More and more studies discovered that cervical microbiota (CM) composition correlated with HPV infection and the development of cervical cancer. However, more studies need to be implemented to clarify the complex interaction between microbiota and the mechanism of disease development, especially in a specific area of China.Materials and methodsIn this study, 16S rDNA sequencing was applied on 276 Thin-prep Cytologic Test (TCT) samples of patients from the Sanmenxia area. Systematical analysis of the microbiota structure, diversity, group, and functional differences between different HPV infection groups and age groups, and co-occurrence relationships of the microbiota was carried out.ResultsThe major microbiota compositions of all patients include Lactobacillus iners, Escherichia coli, Enterococcus faecalis, and Atopobium vaginae at species level, and Staphylococcus, Lactobacillus, Gardnerella, Bosea, Streptococcus, and Sneathia in genus level. Microbiota diversity was found significantly different between HPV-positive (Chao1 index: 98.8869, p < 0.01), unique-268 infected (infections with one of the HPV genotype 52, 56, or 58, 107.3885, p < 0.01), multi-268 infected (infections with two or more of HPV genotype 52, 56, and 58, 97.5337, p = 0.1012), other1 (94.9619, p < 0.05) groups and HPV-negative group (83.5299). Women older than 60 years old have higher microbiota diversity (108.8851, p < 0.01, n = 255) than younger women (87.0171, n = 21). The abundance of Gardnerella and Atopobium vaginae was significantly higher in the HPV-positive group than in the HPV-negative group, while Burkholderiaceae and Mycoplasma were more abundant in the unique-268 group compared to the negative group. Gamma-proteobacteria and Pseudomonas were found more abundant in older than 60 patients than younger groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) analysis revealed the effects on metabolism by microbiota that the metabolism of cells, proteins, and genetic information-related pathways significantly differed between HPV-negative and positive groups. In contrast, lipid metabolism, signal transduction, and cell cycle metabolism pathway significantly differed between multi-268 and negative groups.ConclusionThe HPV infection status and age of women were related to CM’s diversity and function pathways. The complex CM co-occurrent relationships and their mechanism in disease development need to be further investigated.

Association between common vaginal and HPV infections and results of cytology test in the Zhoupu District, Shanghai City, China, from 2014 to 2019

BackgroundHPV (human papillomavirus) is an important cause of cervical cancer. Cervical-vaginal infection with pathogens, such as herpes simplex virus (HSV), bacterial vaginosis Trichomonas vaginalis and vaginal candidiasis could be a cofactor. This study aimed to assess the relationship between vaginal infection with HPV genotype and cytology test results and analyze the relationship between vaginal and HPV infections and cervical cancer.MethodsWe performed a district-based study to elucidate the relationship among the vaginal and HPV infections and cervical cancer. We collected the cervical exfoliation data of 23,724 women admitted to the Shanghai Zhoupu Hospital and received ThinPrep cytology test (TCT) and HPV detection between 2014 and 2019.ResultsTotal vaginal infection rate was 5.3%, and the HPV-positive group had a slightly higher vaginal infection rate than the HPV-negative group (P < 0.01). The incidence rate of cervical intraepithelial neoplasia or cervical cancer with vaginal infection was higher than without vaginal infection (P < 0.001).ConclusionHPV/vaginal infection-positive women tended to have abnormal results of TCT. Women with vaginal infection were more likely to develop HPV infection. HSV combined with HPV infection was noted as a causal factor for HSIL.

Amide proton transfer imaging for the determination of human papillomavirus status in patients with oropharyngeal squamous cell carcinoma.

The aim of this study was to investigate the utility of amide proton transfer (APT) imaging for the determination of human papillomavirus (HPV) status in patients with oropharyngeal squamous cell carcinoma (SCC). Thirty-one patients with oropharyngeal SCC were retrospectively evaluated. All patients underwent amide proton transfer imaging using a 3T magnetic resonance (MR) unit. Patients were divided into HPV-positive and -negative groups depending on the pathological findings in their primary tumor. In APT imaging, the primary tumor was delineated with a polygonal region of interest (ROI). Signal information in the ROI was used to calculate the mean, standard deviation (SD) and coefficient of variant (CV) of the APT signals (APT mean, APT SD, and APT CV, respectively). The value of APT CV in the HPV-positive group (0.43 ± 0.04) was significantly lower than that in the HPV-negative group (0.48 ± 0.04) (P = .01). There was no significant difference in APT mean (P = .82) or APT SD (P = .13) between the HPV-positive and -negative groups. Receiver operating characteristic (ROC) curve analysis of APT CV had a sensitivity of 0.75, specificity of 0.8, positive predictive value of 0.75, negative predictive value of 0.8, accuracy of 0.77 and area under the curve (AUC) of 0.8. The APT signal in the HPV-negative group was considered heterogeneous compared to the HPV-positive group. This information might be useful for the determination of HPV status in patients with oropharyngeal SCC.

Expression patterns of uPAR, TF and EGFR and their potential as targets for molecular imaging in oropharyngeal squamous cell carcinoma.

The clinical introduction of molecular imaging for the management of oropharyngeal squamous cell carcinoma (OPSCC) relies on the identification of relevant cancer-specific biomarkers. The application of three membrane-bound receptors, namely urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and EGFR have been previously explored for targeted imaging and therapeutic strategies in a broad range of solid cancers. The present study aimed to investigate the expression patterns of uPAR, EGFR and TF by immunohistochemistry (IHC) to evaluate their potential for targeted imaging and prognostic value in OPSCC. In a retrospective cohort of 93 patients with primary OPSCC, who were balanced into the 45 human papillomavirus (HPV)-positive and 48 HPV-negative groups, the IHC-determined expression profiles of uPAR, TF and EGFR in large biopsy or tumor resection specimens were analyzed. Using the follow-up data, overall survival (OS) and recurrence-free survival were measured. Specifically, associations between survival outcome, biomarker expression and clinicopathological factors were examined using Cox proportional hazards model and log-rank test following Kaplan-Meier statistics. After comparing the expression pattern of biomarkers within the tumor compartment with that in the adjacent normal tissues, uPAR and TF exhibited a highly tumor-specific expression pattern, whereas EGFR showed a homogeneous expression within the tumor compartment as well as a consistent expression in the normal mucosal epithelium and salivary gland tissues. The positive expression rate of uPAR, TF and EGFR in the tumors was 98.9, 76.3 and 98.9%, respectively. No statistically significant association between biomarker expression and survival outcome could be detected. Higher uPAR expression levels had a trend towards reduced OS according to results from univariate analysis (P=0.07; hazard ratio=2.01; 95% CI=0.92-4.37). Taken together, these results suggest that uPAR, TF and EGFR may be suitable targets for molecular imaging and therapy in OPSCC. In particular, uPAR may be an attractive target owing to their high positive expression rates in tumors and a highly tumor-specific expression pattern.

Comprehensive Analysis of the Carcinogenic Process, Tumor Microenvironment, and Drug Response in HPV-Positive Cancers.

Human papillomavirus (HPV) is a common virus, and about 5% of all cancers worldwide is caused by persistent high-risk HPV infections. Here, we reported a comprehensive analysis of the molecular features for HPV-related cancer types using TCGA (The Cancer Genome Atlas) data with HPV status. We found that the HPV-positive cancer patients had a unique oncogenic process, tumor microenvironment, and drug response compared with HPV-negative patients. In addition, HPV improved overall survival for the four cancer types, namely, cervical squamous cell carcinoma (CESC), head and neck squamous cell carcinoma (HNSC), stomach adenocarcinoma (STAD), and uterine corpus endometrial carcinoma (UCEC). The stronger activity of cell-cycle pathways and lower driver gene mutation rates were observed in HPV-positive patients, which implied the different carcinogenic processes between HPV-positive and HPV-negative groups. The increased activities of immune cells and differences in metabolic pathways helped explain the heterogeneity of prognosis between the two groups. Furthermore, we constructed HPV prediction models for different cancers by the virus infection score (VIS) which was linearly correlated with HPV load and found that VIS was associated with drug response. Altogether, our study reveals that HPV-positive cancer patients have unique molecular characteristics which help the development of precision medicine in HPV-positive cancers.

56. Association between vaginal microflora, high-risk hpv infection and hpv e6/e7 expression in high grade cervical intraepithelial neoplasia

Introduction: Role of persistent high-risk HPV infection is essential in development of cervical precancerous lesions. HPV achieves persistent expression by integration of E6 and E7 oncogenes into host genome. Vaginal flora changes can result in proinflammatory environment, that facilitates E6 and E7 expression. Aim of the study was to assess an association between HPV E6/E7 expression, vaginal microflora and high-risk HPV infection in women with high grade cervical intraepithelial neoplasia. Methods: Cross-sectional study was performed in July 2016-June 2017. 62 patients aged 18 to 50 referred for colposcopy to Riga East Clinical University Hospital and with histologically proven CIN 2 or worse were included in the study. Material from cervix was tested for HR HPV DNA types 16/18, 31, 33, 45, 58 and high-risk HPV E6/E7 RNA with real time PCR. Wet mount microscopy of vaginal material was performed using phase-contrast microscope and interpreted according to modified Donders-Schrӧder scale. Data analysis was performed with MS Excel 2019. Results: E6/E7 RNA expression was positive in 58/62 patients. 42/62 patients were HR-HPV positive and 41 of them had E6/E7 expression. From 20 HPV negative patients 17 were E6/E7 positive. 30/62 women had abnormal vaginal flora. In HPV positive group 18/42 had abnormal vaginal flora vs. 12/20 in HPV negative group. (p=ns). In E6/E7 RNA positive group 28/58 had vaginal flora changes vs. 2/4 in E6/E7 negative group. In HR HPV positive/ HPV E6/E7 positive group 18/41 had abnormal vaginal flora vs. 2/3 in HR HPV negative/ HPV E6/E7 negative group (p=ns). Conclusions: In the current study we were not able to find an association between vaginal flora changes, HPV E6/E7 expression and high-risk HPV infection. Larger studies are needed to further asses these associations.

Visual appearance of the uterine cervix differs on the basis of HPV type status in high-grade squamous intraepithelial lesion: the results of a reliable method

BackgroundThis study aimed to evaluate the differences in cervical appearance among different human papillomavirus (HPV) genotypes in patients with high-grade squamous intraepithelial lesions (HSILs).Methods A total of 239 histopathological HSIL patients were included and divided into eight groups on the basis of HPV genotype in this prospective study. We present a reliable imaging method that provides reproducible, sensitive and unbiased assessments of cervical appearance characteristics. Colorimetric and morphometric data of colposcopic patterns after the application of acetic acid and iodine were acquired using ImageJ software and the surrounding normal regions were used as controls.ResultsThe differences in red, green, blue and mean greyscale values in acetowhite epithelium obtained from ImageJ were not significant between the HPV16 and HPV18 groups (P < 0.05). The differences in red, green, and mean greyscale values in iodine staining were significant between the HPV18 and the other groups (P < 0.05). The frequency of the occurrence of the coarse mosaic patterns was significantly different among groups (P < 0.05), reducing in sequence were the HPV16, HPV-negative, HPV18, HPV31/33 and HPV52/58 groups. For the lesion area of HSILs, the HPV-negative group was the largest. The sensitivity of colposcopic impression varied among HPV genotypes (P < 0.01), being lowest in the HPV52 group.ConclusionsAlthough being nonspecific, iodine negativity should be concerned in HPV18-positive lesions which is closely related to glandular epithelium. Vascular patterns in HPV52/58-positive HSIL are quite occult and tend to be missed by colposcopists. HPV-negative lesions are prone to be large and present typical vascular patterns despite being rare.

Identification of differentially expressed genes and pathways for risk stratification in HPV-associated cancers governing different anatomical sites.

Human papillomavirus (HPV) is the major cause of cervical cancer (CC) etiology; its contribution to head and neck cancer (HNC) incidence is steadily increasing. As individual patients' response to the treatment of HPV-associated cancer is variable, there is a pressing need for the identification of biomarkers for risk stratification that can help determine the intensity of treatment. We have previously reported a novel prognostic and predictive indicator (HPPI) scoring system in HPV-associated cancers regardless of anatomical location by analyzing The Cancer Genome Atlas and Gene Expression Omnibus databases. In the present study, we comprehensively investigated the association of group-specific expression patterns of common differentially expressed genes (DEGs) between high- and low-risk groups in HPV-associated CC and HNC, identifying molecular biomarkers and pathways for risk stratification. Among the 174 identified DEGs, the expression of genes associated with extracellular matrix (ECM)-receptor interaction pathway (ITGA5, ITGB1, LAMB1, and LAMC1) was increased in high-risk groups in both HPV-associated CC and HNC, while the expression of genes associated with T-cell immunity (CD3D, CD3E, CD8B, LCK, and ZAP70) was decreased and vice versa. The individual genes showed significant prognostic impact on HPV-associated cancers but not on HPV-negative cancers. The expression levels of identified genes were similar between HPV-negative and HPV-associated high-risk groups with distinct expression patterns only in HPV-associated low-risk groups. Each group of genes showed negative correlations and distinct patterns of immune cell infiltration in tumor microenvironments. These results allowed us to identify molecular biomarkers and pathways for risk stratification in HPV-associated cancers regardless of anatomical location. The identified targets were found to be selectively working in only HPV-associated cancers and not in HPV-negative cancers, indicating the possibility of selective targets governing HPV-infective tumor microenvironments.

Decreased CD1a + and CD83 + cells in tonsillar squamous cell carcinoma regardless of HPV status.

Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer.Objective:To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection.Methodology:CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018).Results:There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004).Conclusion:Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.

MORPHOLOGICAL CHANGES IN SOFT PALATINE TISSUES STANDING BEHIND OBSTRUCTIVE SLEEP APNEA SYNDROME: GENERAL PATTERN AND ROLE OF HUMAN PAPILLOMA VIRUS

snoring and obstructive sleep apnea syndrome (OSAS) are a serious medical problem, as they lead to a complex of complications from various body systems, disrupt the socio-economic sphere and stigmatize patients. To date, a set of treatments has been developed, the most effective of which are conservative therapy using CPAP and surgical interventions - various modifications of uvulopalatopharyngoplasty. However, only a small number of studies have elucidated soft palate tissue pathology in patients with chronic and OSAS. But understanding the morphological changes is one of the key aspects for the development of treatment tactics. The aim of current study is to justify the choice of surgical intervention in the treatment of snoring and OSAS by description of morphological changes of the soft palate and to estimate the impact of HPV infection on the progression of soft palatine remodeling. The study included soft palatine tissue samples, which were removed during surgery for snoring and OSAS in 15 patients. Histological (H&amp;E) and immunohistochemical techniques (Ki-67, p16, Human Papilloma Virus). All patients were divided in two groups according HPV-positivity: 5 persons in HPV-positive group and 10 persons in HPV-negative group. For indicators were estimated: number of cellular layers (CL), number of intraepithelial lymphocytes (per 100 epitheliocytes) (IEL), number of vessels per x100 field (NV), Ki-67 proliferation index (PI). Results shows in HPV+ group: CL - 24,2 (±2,17); IEL - 37,8 (±20,97), NV - 21 (±8,46); PI - 17,6 (±2,51). In HPV- group: CL - 6 (±4,78); IEL - 3,3 (±1,77); NV - 10,7 (±2,67); PI - 7,3 (±2,71). Mann-Whitney criterion shows statistical significant difference between groups for all mentioned indicators. In conclusion: patients with snoring and obstructive sleep apnea syndrome had hypertrophy of the soft palate structures caused by changes in epithelial and connective tissue components. Subepithelial structures underdo the disorganization of connective tissue components with a violation of the histoarchitectonics of collagen fibers, edema and angiomatosis. Thus, the study revealed a number of irreversible pathological processes of soft palate tissues, which is the basis for the choice of surgical treatment tactics including the resection of excess tissue. At the same time HPV-infection leads to more pronounced changes in the epithelial layer and subepithelial tissue with concomitant inflammation that likely to create a negative background for further treatment of OSA syndrome.

Prognostic value of human papillomavirus detection and the eighth edition of the TNM classification staging system in oropharyngeal squamous cell carcinoma: A single-center Polish study

This study aimed to determine human papillomavirus (HPV) status and genotypes, the HPV status-dependent survival, and the applicability of the eighth TNM classification in Polish patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC). All patients with primary OPSCC, diagnosed and treated from 2007 to 2017 at the National Research Institute of Oncology, Warsaw, Poland, who underwent radical radiotherapy were included. The Kaplan-Meier method was deployed to produce 3- and 5-year observed survival (OS) estimates. A total of 110 OPSCC cases were identified. Double positivity for HPV (IHC p16INK4a and HPV-DNA) was recorded in 70.9% of cases, with HPV16 being the most prevalent genotype (96.2%). The disease stage was significantly less advanced in the HPV-related group than in the HPV-negative group (P < .001). Three- and 5-year OS in HPV-related carcinoma was 80.7% and 74.0%, respectively; in the HPV-negative group, OS was 52.9% and 48.5%. OS rates were associated with HPV status, tumor stage, and disease stage according to the eighth edition TNM classification. The majority of Polish patients with OPSCC are HPV16-positive. In HPV-related OPSCC, survival rates are significantly higher than in HPV-negative OPSCC. The findings support the requirement of HPV testing in Polish patients with OPSCC because HPV-positive status influences tumor prognosis.

Pretreatment C-Reactive Protein/Albumin Ratio is Associated With Poor Survival in Patients With 2018 FIGO Stage IB-IIA HPV-Positive Cervical Cancer.

Objectives: The present study aimed to identify the predictive value of inflammatory indexes stratified according to human papillomavirus (HPV) infection status in women with FIGO 2018 stage IB∼IIA cervical cancer. We also explored the influences of HPV infection status on the survival of cervical cancer patients. Methods: We collected data for 583 women with stage IB∼IIA cervical cancer in Sun Yat-sen University Cancer Center between 2009 and 2017. The t-test, chi-squared (χ2) test and Fisher’s exact test were applied to compare the differences of inflammatory indexes and clinicopathological features between HPV-positive and HPV-negative groups. Univariate and multivariate analyses were used to identify clinicopathological factors that were associated with the prognosis of cervical cancer patients. Results: There were no differences in overall survival (OS) and progression-free survival (PFS) between HPV-positive and HPV-negative groups. In HPV-positive group, the maximum tumor size, neoadjuvant chemotherapy and the body mass index (BMI) correlated significantly with C-reactive protein/albumin ratio (CAR). The maximum tumor size and the prognostic nutritional index (PNI) correlated significantly with the platelet-lymphocyte ratio (PLR). The maximum tumor size, neoadjuvant chemotherapy and PLR correlated significantly with PNI. Univariate and multivariate analyses showed that the depth of tumor invasion (HR: 3.651, 95% CI: 1.464–9.103, p = 0.005; HR: 2.478, 95% CI: 1.218–5.043, p = 0.012) and CAR (HR: 5.201, 95% CI: 2.080–13.004, p < 0.0001; HR: 2.769, 95% CI: 1.406–5.455, p = 0.003) were independent predictors of poor OS and PFS. PNI was an independent protective factor of OS (HR: 0.341, 95% CI: 0.156–0.745, p = 0.007). PLR was an independent factor of PFS (HR: 1.991, 95% CI: 1.018–3.894, p = 0.044). In HPV-negative group, BMI correlated significantly with CAR. Only depth of invasion (HR: 9.192, 95% CI: 1.016–83.173, p = 0.048) was the independent predictor of poor OS, and no inflammation indexes were independent predictors of prognosis. Conclusion: In patients with HPV-positive cervical cancer, depth of invasion, PNI and CAR are independent factors of OS, and depth of invasion, PLR and CAR are independent factors for PFS. For patients with HPV-negative disease, no inflammation indexes had predictive value for prognosis. The predictive value of inflammation indexes on prognosis is more significant in patients with HPV-positive cervical cancer. Stratification of HPV infection status promotes a more precise clinical application of inflammation indexes, thus improving their accuracy and feasibility.