BACKGROUND: Standard treatment of oropharyngeal squamous cell carcinoma (OPSCC) is associated with high morbidity, whereas immunotherapeutic approaches using PD-1:PD-L1 checkpoint blockade only show moderate response rates in OPSCC patients. Therefore, a better stratification of patients and the development of novel therapeutic protocols are crucially needed. The importance of tumor-infiltrating B cells (TIL-Bs) in shaping antitumor immunity remains unclear; therefore, we analyzed frequency, phenotype, prognostic value and possible roles of TIL-Bs in OPSCC. METHODS: We utilized transcriptomic analysis of immune response-related genes in 18 OPSCC samples with respect to human papillomavirus (HPV) status. The density and localization of CD20+, CD8+ and DC-LAMP+ cells were subsequently analyzed in 72 tissue sections of primary OPSCC samples in relation to patients' prognosis. The immunohistochemical approach was supplemented by flow cytometry-based analysis of phenotype and functionality of TIL-Bs in freshly resected primary OPSCC tissues. RESULTS: We observed significantly higher expression of B cell-related genes and higher densities of CD20+ B cells in HPV-associated OPSCC samples. Interestingly, CD20+ TIL-Bs and CD8+ T cells formed non-organized aggregates with interacting cells within the tumor tissue. The densities of both intraepithelial CD20+ B cells and B cell/CD8+ T cell interactions showed prognostic significance, which surpassed HPV positivity and CD8+ TIL density in stratification of OPSCC patients. High density of TIL-Bs was associated with an activated B cell phenotype, high CXCL9 production and high levels of tumor-infiltrating CD8+ T cells. Importantly, the abundance of direct B cell/CD8+ T cell interactions positively correlated with the frequency of HPV16-specific CD8+ T cells, whereas the absence of B cells in tumor-derived cell cultures markedly reduced CD8+ T cell survival. CONCLUSIONS: Our results indicate that high abundance of TIL-Bs and high density of direct B cell/CD8+ T cell interactions can predict patients with excellent prognosis, who would benefit from less invasive treatment. We propose that in extensively infiltrated tumors, TIL-Bs might recruit CD8+ T cells via CXCL9 and due to a highly activated phenotype contribute by secondary costimulation to the maintenance of CD8+ T cells in the tumor microenvironment.

• MeSH
• adjuvantní chemoradioterapie MeSH
• aktivace lymfocytů MeSH
• B-lymfocyty imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• dlaždicobuněčné karcinomy hlavy a krku imunologie   mortalita   terapie   virologie   MeSH
• dospělí MeSH
• infekce papilomavirem imunologie   mortalita   terapie   virologie   MeSH
• Kaplanův-Meierův odhad MeSH
• kohortové studie MeSH
• krční disekce MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezibuněčná komunikace imunologie   MeSH
• nádorové mikroprostředí imunologie   MeSH
• nádory orofaryngu imunologie   mortalita   terapie   virologie   MeSH
• orofarynx patologie   chirurgie   MeSH
• Papillomaviridae imunologie   izolace a purifikace   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• senioři MeSH
• tumor infiltrující lymfocyty imunologie   MeSH
• výběr pacientů MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Lidský papilomavirus (human papilloma virus, HPV) je dvouvláknový DNA virus, s tropismem k epiteliím pokožky a sliznic genitálního traktu nebo horních cest dýchacích. Je přenášen hlavně pohlavním stykem a vstupuje do těla skrz mikrotraumata. Na základě schopnosti papilomavirů indukovat karcinomy byly rozděleny na nízkorizikové LR (low-risk) a vysokorizikové HR (high-risk). Nízkorizikové typy jsou zodpovědné za virové bradavice (veruca). Vysokorizikové typy jsou spojovány s malignitami anogenitálních oblastí a oblastí hlavy a krku. Na základě změny profilu pacientů s HNSCC (head and neck squamous cell carcinoma, karcinom skvamózních buněk hlavy a krku) se uvažuje, že papilomaviry zvyšují riziko pro vznik karcinomů a jsou kauzálně spojené s vývojem HNSCC, nezávisle na dvou hlavních karcinogenech - tabáku a alkoholu. HPV-pozitivní pacienti s HNSCC mají odlišnou molekulární charakteristiku a jsou spojováni s lepší prognózou, reakcí na léčbu a s vyšším celkovým přežitím. Pacienti s HNSCC mohou profitovat z anti-EGFR terapie cetuximabem, avšak doposud bez definovaných prediktorů, jako je tomu u kolorektálního karcinomu.

Human papillomavirus (HPV) is a double stranded DNA virus with a tropism to skin epithelia and mucosa of genital tract or upper airways. It is transmitted mainly by sexual intercourse and enters the body through microscopic injuries. Based on their ability to induce cancer these were further divided into low-risk and high-risk subgroups. Low-risk subgroup is responsible for the presence of viral verrucas. The high-risk subgroup is related to malignant anogenital dysplasias and also dysplasias in areas of head and neck. It is speculated that based on the change in profile of patients with HNSCC (head and neck squamous cell carcinoma) papilloma viruses increase the risk of cancer development and are causally related to the development of HNSCC independent of the two main carcinogens - tabaco and alcohol. Interestingly HPV positive HNSCC patients have dissimilar molecular characteristics and are related to better prognosis, therapy response and higher overall survival. They may profit from anti-EGFR therapy by cetuximab, but without defined predictors, such as those known in CRC patients.

• MeSH
• biologická terapie metody   trendy   MeSH
• cetuximab aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• erbB receptory antagonisté a inhibitory   terapeutické užití   MeSH
• farmakoterapie metody   trendy   MeSH
• kouření tabáku škodlivé účinky   MeSH
• lidé MeSH
• lidský papilomavirus 16 * genetika   imunologie   patogenita   MeSH
• nádory hlavy a krku * epidemiologie   etiologie   virologie   MeSH
• otorinolaryngologické chirurgické výkony metody   trendy   MeSH
• Papillomaviridae * genetika   imunologie   růst a vývoj   MeSH
• pití alkoholu škodlivé účinky   MeSH
• radioterapie metody   škodlivé účinky   trendy   MeSH
• rizikové faktory MeSH
• spinocelulární karcinom epidemiologie   etiologie   terapie   MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

OBJECTIVE: The human papillomavirus (HPV) causes recurrent respiratory papillomatosis (RRP). Although HPV prevalence is high, the incidence of papillomatosis is low. Thus, factors other than HPV infection probably contribute to RRP. This study investigated whether patients with papillomatosis are more often infected with herpes simplex virus type 2 and chlamydia trachomatis (ChT) and whether laryngopharyngeal reflux (LPR) occurs in this group of patients more often. DESIGN: Prospective case-control study. SETTING: Department of Otorhinolaryngology of University Hospital. PARTICIPANTS: The study included 20 patients with adult-onset RRP and 20 adult patients with vocal cord cyst and no pathology of laryngeal mucosa (control group). MAIN OUTCOME MEASURES: Immunohistochemical analysis of pepsin, HPV, herpes simplex virus type 2 and ChT was performed in biopsy specimens of laryngeal papillomas and of healthy laryngeal mucosa (control group) obtained from medial part of removed vocal cord cyst during microlaryngoscopy procedures. RESULTS: Pathologic LPR (pepsin in tissue) was diagnosed in 8/20 (40.0%) patients with papillomatosis and in 0/20 control patients (P = .003). Herpes simplex virus type 2 was present in 9/20 (45.0%) patients with papillomatosis and in 0/20 control patients (P = .001). Five specimens were positive for both pepsin and herpes simplex virus type 2. No samples were positive for ChT. There were no significant differences between groups for age, body mass index, diabetes mellitus and gastrooesophageal reflux disease. Tobacco exposure was not more frequent in RRP group either (P = .01). CONCLUSIONS: Results show that LPR and herpes simplex virus type 2 are significantly more often present in patients with RRP. LPR and herpes simplex virus type 2 might activate latent HPV infection and thereby be possible risk factors for RRP.

• MeSH
• dospělí MeSH
• herpes simplex komplikace   epidemiologie   MeSH
• incidence MeSH
• infekce dýchací soustavy epidemiologie   etiologie   MeSH
• infekce papilomavirem epidemiologie   etiologie   MeSH
• laryngofaryngeální reflux komplikace   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský herpesvirus 2 imunologie   MeSH
• mladý dospělý MeSH
• Papillomaviridae imunologie   MeSH
• prevalence MeSH
• prospektivní studie MeSH
• protilátky virové analýza   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

• Klíčová slova
• nonavalentní vakcína,
• MeSH
• dysplazie děložního hrdla prevence a kontrola   MeSH
• infekce papilomavirem * prevence a kontrola   MeSH
• kondylomata akuminata prevence a kontrola   MeSH
• lidé MeSH
• nádory anu prevence a kontrola   MeSH
• nádory děložního čípku * prevence a kontrola   MeSH
• očkovací programy MeSH
• Papillomaviridae genetika   imunologie   MeSH
• rekombinantní kvadrivalentní vakcína proti lidskému papilomaviru typu 6, 11, 16, 18 * aplikace a dávkování   terapeutické užití   MeSH
• vakcinace MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Importance: Human papillomavirus (HPV) infections cause anogenital cancers and warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for 90% of genital warts. Objective: To determine whether HPV type-specific antibody responses would be noninferior among girls and boys aged 9 to 14 years after receiving 2 doses of the 9-valent HPV vaccine compared with adolescent girls and young women aged 16 to 26 years receiving 3 doses. Design, Setting, and Participants: Open-label, noninferiority, immunogenicity trial conducted at 52 ambulatory care sites in 15 countries. The study was initiated on December 16, 2013, with the last participant visit for this report on June 19, 2015. Five cohorts were enrolled: (1) girls aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (2) boys aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (3) girls and boys aged 9 to 14 years to receive 2 doses 12 months apart (n = 301); (4) girls aged 9 to 14 years to receive 3 doses over 6 months (n = 301); and (5) a control group of adolescent girls and young women aged 16 to 26 years to receive 3 doses over 6 months (n = 314). Interventions: Two doses of the 9-valent HPV vaccine administered 6 or 12 months apart or 3 doses administered over 6 months. Main Outcomes and Measures: The primary end point was prespecified as the antibody response against each HPV type assessed 1 month after the last dose using a competitive immunoassay. Each of the three 2-dose regimens was compared with the standard 3-dose schedule in adolescent girls and young women using a noninferiority margin of 0.67 for the ratio of the antibody geometric mean titers. Results: Of the 1518 participants (753 girls [mean age, 11.4 years]; 451 boys [mean age, 11.5 years]; and 314 adolescent girls and young women [mean age, 21.0 years]), 1474 completed the study and data from 1377 were analyzed. At 4 weeks after the last dose, HPV antibody responses in girls and boys given 2 doses were noninferior to HPV antibody responses in adolescent girls and young women given 3 doses (P < .001 for each HPV type). Compared with adolescent girls and young women who received 3 doses over 6 months, the 1-sided 97.5% CIs for the ratio of HPV antibody geometric mean titers at 1 month after the last dose across the 9 HPV subtypes ranged from 1.36 to ∞ to 2.50 to ∞ for girls who received 2 doses 6 months apart; from 1.37 to ∞ to 2.55 to ∞ for boys who received 2 doses 6 months apart; and from 1.61 to ∞ to 5.36 to ∞ for girls and boys who received 2 doses 12 months apart. Conclusions and Relevance: Among girls and boys aged 9 to 14 years receiving 2-dose regimens of a 9-valent HPV vaccine separated by 6 or 12 months, immunogenicity 4 weeks after the last dose was noninferior to a 3-dose regimen in a cohort of adolescent girls and young women. Further research is needed to assess persistence of antibody responses and effects on clinical outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01984697.

• MeSH
• časové faktory MeSH
• dítě MeSH
• dospělí MeSH
• fyziologie výživy seniorů MeSH
• genotyp MeSH
• imunogenicita vakcíny MeSH
• infekce papilomavirem prevence a kontrola   MeSH
• kohortové studie MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• očkovací schéma * MeSH
• Papillomaviridae genetika   imunologie   MeSH
• sexuální faktory MeSH
• specificita protilátek MeSH
• vakcíny proti papilomavirům aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

An increased rate of second nonmelanoma skin cancers is found in immunocompromised patients. Epidemiological and molecular data implicate ultraviolet radiation as the major risk factor. In addition, there is increasing evidence supporting the role of human papillomavirus (HPV) in the pathogenesis of premalignant and malignant skin lesions in both immunocompetent and immunocompromised patients. In a retrospective cross-sectional study, the authors examined the expression of p16 by immunohistochemistry and the presence of mucosal (α-genus) and cutaneous/epidermodysplasia verruciformis (β-genus) HPV DNA by polymerase chain reaction in 29 biopsy specimens of extragenital/extraungual Bowen disease (BD) from 24 Eastern European white immunocompromised patients. Furthermore, the author evaluated the association between the expression of p16 protein and the presence of HPV DNA. Among 25 specimens from 21 patients evaluable by polymerase chain reaction, HPV DNA was detected in 10 (40%) BD lesions from 9 patients. Beta-HPV predominated over alpha-HPV types. Among 29 immunohistochemically evaluable BD specimens, 22 lesions (∼76%) from 20 patients were scored as p16 positive. HPV DNA-positive and HPV DNA-negative lesions displayed the same proportion of p16 positivity (80%) and no correlation was found between the HPV DNA presence and the p16 expression status. Our pilot study demonstrated that β-HPV infections predominate in BD cases diagnosed among immunocompromised patients, although high- and low-risk mucosal (alpha) HPV genotypes may be detected in a minority of cases. In contrast to anogenital HPV-associated lesions, positive p16 expression is not a reliable marker of high-risk α-HPV infection in BD cases, as it can be also detected in β-HPV infected and HPV-negative cases.

• MeSH
• biopsie MeSH
• Bowenova nemoc chemie   imunologie   virologie   MeSH
• DNA testy na papilomavirus MeSH
• DNA virů genetika   MeSH
• hostitel s imunodeficiencí * MeSH
• imunohistochemie MeSH
• infekce papilomavirem imunologie   virologie   MeSH
• inhibitor p16 cyklin-dependentní kinasy analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory kůže chemie   imunologie   virologie   MeSH
• Papillomaviridae genetika   imunologie   patogenita   MeSH
• pilotní projekty MeSH
• prediktivní hodnota testů MeSH
• prekancerózy chemie   imunologie   virologie   MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• virová transformace buněk MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVES: The assessment of the prevalence of antibodies to human papillomaviruses (HPV) in the healthy population is essential for effective planning of HPV vaccine implementation into the preventive programmes for HPV-associated diseases and for the prospective monitoring of the impact of HPV vaccines in the Czech population. METHODS: The seropositivity for HPV-6, 11, 16, 18, 31 and 33 virus-like particles was determined in sera from 3150 healthy individuals (age range 6-76 years) by means of enzyme-linked immunoassay. RESULTS: The seroprevalences for HPV-6, 11, 16, 18, 31 and 33 were 23.8%, 15.2%, 14.5%, 9.9%, 16.4% and 9.6% in women and 18.4%, 13.7%, 6.5%, 5.4%, 6.1% and 4.3% in men. For both genders, except for HPV11, these rates were age dependent. The prevalence of antibodies to HPV-16 and/or 18 reached the maximum of 27.0% in women 30-39 years of age and of 14.4% in men 50-59 years of age. The highest proportion of individuals' seropositive for any of the vaccine types HPV-6/11/16/18 was in 30- to 39-year-old women (50.0%) and in ≥ 60-year-old men (37.6%). Antibodies specific for vaccine HPV types were detected in 18.0% of children 6- to 14-year-old but in 26.4%, those older than 14 years. CONCLUSIONS: The data reveal age-specific differences in the HPV seropositivity rates between healthy women and men and support the implementation of HPV vaccination in the Czech Republic before the age of 13.

• MeSH
• dítě MeSH
• dospělí MeSH
• ELISA MeSH
• infekce papilomavirem epidemiologie   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• Papillomaviridae imunologie   MeSH
• předškolní dítě MeSH
• protilátky virové krev   MeSH
• průřezové studie MeSH
• senioři MeSH
• séroepidemiologické studie MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

• MeSH
• infekce papilomavirem * dějiny   terapie   MeSH
• lidé MeSH
• mladiství MeSH
• nádory děložního čípku prevence a kontrola   MeSH
• očkovací schéma MeSH
• Papillomaviridae imunologie   patogenita   MeSH
• pediatrie MeSH
• prekancerózy MeSH
• primární prevence MeSH
• vakcinace metody   trendy   MeSH
• vakcíny proti papilomavirům * dějiny   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH

The association of high-risk human papillomaviruses (HR HPVs) with tonsillar cancer (TC) has been documented. Because patients with HPV-associated tumors show better survival rates, modification of their treatment regimen is being considered. It is therefore crucial to find markers for the identification of patients whose tumors are linked to viral infection. A cohort of 109 patients with primary TC was screened for HPV DNA presence in the tumor tissues and HPV-specific antibodies in sera. Data regarding risk factors and clinical parameters were collected. Forty-five specimens were analyzed for the expression of viral E6 and E2-region mRNA, and the p16 and p53 protein expression status was assessed by immunohistochemistry. The overall prevalence of HPV DNA in TC tissues was 65.1%. Ninety-three percent of HR HPV DNA-positive samples expressed E6*I mRNA. E2-region mRNA expression was detected in 36% of positive samples, which implies that the virus is integrated in 64% of HPV DNA/RNA-positive tumors. p16 overexpression and the presence of antibodies specific to HPV16 E6/E7 oncoproteins correlated well with HPV DNA and RNA presence. The disease-specific survival rate of patients with HPV DNA-positive tumors was significantly higher than that of HPV DNA-negative patients. In addition to providing further evidence of the involvement of HPV infection in the etiopathogenesis of a proportion of TC cases, our study demonstrates that p16 immunostaining and anti-E6/E7 antibodies as surrogate markers of HPV involvement represent specific, sensitive and clinically accessible assays for the identification of TC patients who have a considerably better prognosis.

• MeSH
• DNA virů metabolismus   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• infekce onkogenními viry metabolismus   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• Papillomaviridae genetika   imunologie   patogenita   MeSH
• polymerázová řetězová reakce MeSH
• prognóza MeSH
• protilátky virové krev   MeSH
• tonzilární nádory metabolismus   patologie   virologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• nádory děložního čípku etiologie   prevence a kontrola   MeSH
• Papillomaviridae imunologie   patogenita   účinky léků   MeSH
• primární prevence metody   MeSH
• vakcíny proti papilomavirům aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH