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Marker di staminalità nei carcinomi squamocellulari del cavo orale e orofaringe in relazione al sito di origine e a infezione da HPV: implicazioni cliniche.In questo studio è stata esaminata l’espressione di potenziali marcatori di staminalità nei carcinomi della testa e collo (HNSCC) per valutarne il loro possibile ruolo clinico. Sono stati arruolati 69 carcinomi squamocellulari del cavo orale (OSCC) e dell’orofaringe (OPSCC) primitivi e non precedentemente sottoposti a trattamento, raccogliendo i dati anagrafici, clinici e sul follow up. Abbiamo valutato l’eventuale infezione da HPV e l’espressione di 5 potenziali marker di staminalità (CD44, CD133, Oct-4, Nanog, and Sox-2). Gli OPSCC positivi per HPV hanno mostrato minor espressione di Nanog, mentre la sua espressione citoplasmatica è stata associata con una prognosi significativamente peggiore negli OPSCC ma non in OSCC. La colorazione di Sox-2 si è rivelata più intensa tra gli OPSCC, e la sua espressione nucleare è associata con una peggiore prognosi. L’espressione di Nanog è associata a OPSCC HPV-negativi e può avere un ruolo come marker diagnostico surrogato. In conclusione il profilo di espressione di alcuni marker di cellule staminali nei HNSCC sembra essere differente a seconda del sito di origine del tumore e dell’infezione da HPV. Inoltre Nanog e Sox-2 potrebbero presentare un significato prognostico.The expression of potential stem cell markers in HNSCCs was investigated to assess their potential clinical role. 69 primary, previously untreated oral (OSCC) and oropharyngeal squamous cell carcinomas (OPSCC) were enrolled; personal, clinical and follow-up data were collected. HPV infection and expression of 5 potential stem cell markers (CD44, CD133, Oct-4, Nanog, and Sox-2) were evaluated. HPV+ OPSCC showed lower expression of Nanog. The cytoplasmic expression of Nanog was associated with significantly worse prognosis in OPSCC, but not in OSCC. Sox-2 staining was more intense among OPSCCs. Sox-2 nuclear staining was associated with worse prognosis. Nanog expression was associated with HPV- OPSCC and may have a role as a surrogate diagnostic marker. In general, the expression profile of some stem cell markers in HNSCC seems to vary according to the site of origin and HPV infection. Nanog and Sox-2 may also have prognostic value.

Background Recent studies have shown a 13-fold increase of oropharyngeal cancer in the presence of HPV, while α-HPV detection seems to be rare in oral cavity in comparison to anal or cervical district, many novel β and γ types have been isolated in this anatomical site suggesting a wide tropism range. Currently, there are no guidelines recommending HPV oral cavity screening as a mandatory test, and it remains unknown which HPV types should be included in HPV screening programs. Our goal was to assess HPV prevalence in oropharyngeal, anal, and cervical swabs using different sets of primers,which are able to amplify α, β, γ HPV types. Methods We analysed the presence of HPV DNA in oropharyngeal (n = 124), anal (n = 186), cervical specimens (n = 43) from HIV positive and negative patients using FAP59/64 and MY09/11 primers. All untyped strains were genetically characterized through PCR amplification and direct sequencing of partial L1 region, and the resulting sequences were classified through phylogenetic analysis. Results HPV prevalence was 20.9% in 124 oropharyngeal swab samples, including infections with multiple HPV types (5.6%). HPV prevalence in this anatomical site was significantly associated with serostatus: 63.3%in HIV positive and 36.3% in HIV negative patients (p

Tumori glave i vrata nalaze se na šestom mjestu po učestalosti tumora u svijetu. U posljednih nekoliko desetljeća zabilježen je porast broja oboljelih od karcinoma orofarinksa u razvijenim zemljama svijeta, dok ostatak tumora područja glave i vrata bilježi pad ili stagnaciju. Prema istraživanjima, glavni je uzrok porast broja oboljelih od HPV pozitivnih karcinoma orofarinksa. Glavni čimbenik rizika za nastanak HPV pozitivnog karcinoma orofarinksa je dugotrajna infekcija visokorizičnim tipovima HPV virusa (16 i 18) stečena, u većini slučajeva, rizičnim seksualnim ponašanjem. Način na koji infekcija napreduje u karicnogenezu zahtijeva nekoliko mehanizama poput bijega od imunološkog odogovora, aktivaciju ranih virusnih onkogena E6 i E7 u bazalnim epitelnim stanicama, poremećaj stabilnosti genoma domaćina, integraciju virusne DNA u genom domaćina te mnoge druge još nedovoljno istražene mehanizme. S obzirom na specifične karakteristike bolesnika oboljelih od HPV pozitivnih tumora orofarinksa, a to su mlađa životna dob, viši socioekonomski status, oženjeni, viši stupanj obrazovanja, nepušači i umjereni konzumenti alkoholnih pića, te na bolji odgovor na liječenje i bolju prognozu, javila se potreba za procjenom dosadašnjih terapijskih mogućnosti i njihovom prilagodbom čime bi se smanjio rizik za nastanak nuspojava uz što veću učinkovitost u izlječenju od karcinoma. Ovaj pregledni rad opisuje trenutne terapijske mogućnosti u liječenju bolesnika oboljelih od HPV pozitivnih karcinoma orofarinksa uz dodatak opisa novih metoda liječenja koje su još uvijek u fazi istraživanja učinkovitosti., Head and neck carcinoma is the sixth most common cancer worldwide. In the last few decades an increase in the incidence of oropharyngeal carcinoma has been noted in developed countries, while the incidence of other head and neck tumors has been decreasing or stagnating. According to researches, the main cause of it is the increase in number of HPV- positive oropharyngeal carcinoma. The main risk factor for developing HPV-positive oropharyngeal carcinoma is chronic infection with high-risk HPV genotypes (16 and 18), mostly acquired via risky sexual behavior. Progression of infection into a carcinogenesis requires few mechanisms such as evasion of immune response, the activation of early viral oncogenes E6 and E7 in basal epithilial cells, the deregulation of cell-cycle and genom instability, viral DNA integration and other still unsufficiently researched mechanisms. Regarding specific patient's charachteristics, such as younger age, higher socioeconomic status, married, higher education level, non-smokers, non-drinkers or moderate drinkers, and better treatment response and prognosis in general, there has been a need for evaluation of current therapeutic options and their adjustment in order to decrease the risk of side effects with maximum efficiency of carcinoma eradication. This review paper describes current therapeutic options in the treatment of HPV-positive oropharyngeal carcinoma with addition of newest methods that are still in the phase of efficiency estimation.

O Papilomavírus Humano tem alta incidência na população. O objetivo deste trabalho é o estudo dos resultados encontrados no exame anatomo-patológico e no PCR das formas clínica e subclínica da infecção anal por HPV em quatro grupos de pacientes. MÉTODO: Foram estudados 10 pacientes com prurido anal idiopático, seis com infecção genital pelo HPV, tratada, seis com condiloma anal tratado e oito com condiloma anal. As verrugas foram biopsiadas nos oito pacientes com condiloma e feito exame de anuscopia de alta resolução com biópsia dirigida nos outros 22 pacientes. O material foi encaminhado para exame anátomo-patológico e depois, a partir do mesmo bloco de parafina, foi feito o exame de PCR. Resultados: O anátomo-patológico foi positivo para HPV em todos os pacientes, sendo que nos oito com condiloma confirmou-se a forma clínica e em 22 diagnosticou-se a subclínica com 13 casos de neoplasia intraepitelial associada. O PCR foi positivo em 91,9% dos 22 pacientes da forma subclínica ao anátomo-patológico e em 87,5% dos oito pacientes da forma clínica. O tipo predominante nos casos de HPV anal subclínico foi o 16 e o predominante nas verrugas foi o 11. CONCLUSÕES: O exame anátomo-patológico foi positivo para HPV em todos os pacientes, propiciando também o diagnóstico de 13 casos de neoplasia intraepitelial, sendo dois de carcinoma "in situ". O PCR foi positivo em 91,9% dos pacientes da forma subclínica ao anátomo-patológico e em 87,5% da forma clínica ao anátomo-patológico. O tipo predominante da forma subclinica foi o 16 e das verrugas foi o 11.The purpose of this study is to analyze the results found in the pathological examination and PCR test for clinical and subclinical HPV anal infections in four groups of patients. Methods: The four groups studied were: ten patients with idiopathic anal pruritus, six with treated HPV genital infection, six with treated anal condyloma, and eight with anal condyloma. Eight patients with condyloma underwent wart biopsy, and high-resolution anoscopy with directed biopsy was performed in the remaining 22 patients. Paraffin wax embedded biopsy specimens were sent to pathological analysis, and later PCR was carried out on the same samples. Results: Through the pathological examination, the presence of HPV is positive in all patients studied: clinically in the eight patients with condyloma, and subclinically in the others 22. Thirteen of these 22 patients presented and associated intraepithelial neoplasia. PCR was positive in 91,9% of the 22 patients those who presented the subclinical infection at pathology examination and 87,5% of the eight patients that presented the clinical infection the most common type of anal subclinical HPV infection was HPV-16 and HPV-11 when warts were presented. Conclusions: Pathological findings related to HPV were presented in all patients studied, and 13 cases were diagnosed two of them were carcinoma in situ. PCR was positive in 91,9% of patients presenting the subclinical infection, and in 87,5% with the clinical infection was HPV-16, and for warts HPV-11.

O Papilomavírus Humano tem alta incidência na população. O objetivo deste trabalho é o estudo dos resultados encontrados no exame anatomo-patológico e no PCR das formas clínica e subclínica da infecção anal por HPV em quatro grupos de pacientes. MÉTODO: Foram estudados 10 pacientes com prurido anal idiopático, seis com infecção genital pelo HPV, tratada, seis com condiloma anal tratado e oito com condiloma anal. As verrugas foram biopsiadas nos oito pacientes com condiloma e feito exame de anuscopia de alta resolução com biópsia dirigida nos outros 22 pacientes. O material foi encaminhado para exame anátomo-patológico e depois, a partir do mesmo bloco de parafina, foi feito o exame de PCR. Resultados: O anátomo-patológico foi positivo para HPV em todos os pacientes, sendo que nos oito com condiloma confirmou-se a forma clínica e em 22 diagnosticou-se a subclínica com 13 casos de neoplasia intraepitelial associada. O PCR foi positivo em 91,9% dos 22 pacientes da forma subclínica ao anátomo-patológico e em 87,5% dos oito pacientes da forma clínica. O tipo predominante nos casos de HPV anal subclínico foi o 16 e o predominante nas verrugas foi o 11. CONCLUSÕES: O exame anátomo-patológico foi positivo para HPV em todos os pacientes, propiciando também o diagnóstico de 13 casos de neoplasia intraepitelial, sendo dois de carcinoma "in situ". O PCR foi positivo em 91,9% dos pacientes da forma subclínica ao anátomo-patológico e em 87,5% da forma clínica ao anátomo-patológico. O tipo predominante da forma subclinica foi o 16 e das verrugas foi o 11. The purpose of this study is to analyze the results found in the pathological examination and PCR test for clinical and subclinical HPV anal infections in four groups of patients. Methods: The four groups studied were: ten patients with idiopathic anal pruritus, six with treated HPV genital infection, six with treated anal condyloma, and eight with anal condyloma. Eight patients with condyloma underwent wart biopsy, and high-resolution anoscopy with directed biopsy was performed in the remaining 22 patients. Paraffin wax embedded biopsy specimens were sent to pathological analysis, and later PCR was carried out on the same samples. Results: Through the pathological examination, the presence of HPV is positive in all patients studied: clinically in the eight patients with condyloma, and subclinically in the others 22. Thirteen of these 22 patients presented and associated intraepithelial neoplasia. PCR was positive in 91,9% of the 22 patients those who presented the subclinical infection at pathology examination and 87,5% of the eight patients that presented the clinical infection the most common type of anal subclinical HPV infection was HPV-16 and HPV-11 when warts were presented. Conclusions: Pathological findings related to HPV were presented in all patients studied, and 13 cases were diagnosed two of them were carcinoma in situ. PCR was positive in 91,9% of patients presenting the subclinical infection, and in 87,5% with the clinical infection was HPV-16, and for warts HPV-11.