Nejvíce citovaný článek - PubMed ID 18440161
High-risk human papillomavirus infection and p16INK4a protein expression in laryngeal lesions
The aim of the study was to investigate prevalence of high-risk human papillomavirus (HR-HPV) infection in sinonasal carcinomas by immunohistochemistry, in situ hybridization, and polymerase chain reaction, detecting p16(INK4a) protein (p16) expression and presence of both HPV DNA and HPV E6/E7 messenger RNA (mRNA). The study comprised 47 males and 26 females, aged 23-83 years (median 62 years), mostly (67 %) with a squamous cell carcinoma (SCC). Of the tumors, 53 % arose in the nasal cavity, 42 % in the maxillary sinus, and 5 % in the ethmoid complex. The follow-up period ranged 1-241 months (median 19 months). HPV16, HPV18, or HPV35 were detected in 18/73 (25 %) tumors, 17 SCCs, and 1 small cell neuroendocrine carcinoma. There was a strong correlation between results of HPV detection methods and p16 expression (p < 0.005). HPV-positive SCCs occurred more frequently in smokers (p = 0.04) and were more frequently p16-positive (p < 0.0001) and nonkeratinizing (p = 0.02), the latter occurring more commonly in nasal cavity (p = 0.025). Median survival for HPV-positive SCC patients was 30 months, while for HPV-negative SCC patients was 14 months (p = 0.23). In summary, we confirm that HR-HPV is actively involved in the etiopathogenesis of a significant subset of sinonasal SCCs. p16 may be used as a reliable surrogate marker for determination of HPV status also in sinonasal SCCs. Although we observed a trend toward better overall survival in HPV-positive SCCs, the prognostic impact of HPV status in sinonasal carcinomas needs to be elucidated by further studies.
- Klíčová slova
- Human papillomavirus (HPV), Nonkeratinizing, RNA, Sinonasal carcinoma, Squamous cell carcinoma, p16 protein,
- MeSH
- dlaždicobuněčné karcinomy hlavy a krku MeSH
- DNA virů analýza MeSH
- dospělí MeSH
- genetická transkripce MeSH
- imunohistochemie MeSH
- inhibitor p16 cyklin-dependentní kinasy MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA analýza MeSH
- nádorové proteiny analýza MeSH
- nádory hlavy a krku mortalita patologie virologie MeSH
- nádory vedlejších dutin nosních mortalita patologie virologie MeSH
- onkogenní proteiny virové genetika MeSH
- Papillomaviridae izolace a purifikace MeSH
- Papillomavirus E7 - proteiny genetika MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- represorové proteiny genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom mortalita patologie virologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CDKN2A protein, human MeSH Prohlížeč
- DNA virů MeSH
- E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
- inhibitor p16 cyklin-dependentní kinasy MeSH
- messenger RNA MeSH
- nádorové proteiny MeSH
- oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
- onkogenní proteiny virové MeSH
- Papillomavirus E7 - proteiny MeSH
- represorové proteiny MeSH
Head and neck squamous cell cancer (HNSCC) includes tumors of various anatomical sites sharing the common etiological factors. However some differences in pathogenesis and prognosis of HNSCC have been hitherto documented. Laryngeal squamous cell carcinoma (LSCC) is one the most common type of the head and neck cancer. The majority of laryngeal cancers are located in the glottic area. P16 was recently documented to be important prognostic marker in many tumors including HNSCC. The aim of our study was to assess the significance of p16 expression in glottic LSCC. Fifty eight patients after surgical treatment of the glottic LSCC were enrolled in the retrospective study. The p16 expression was immunohistochemically detected and semiquantitatively evaluated in tumor tissue. The results were statistically correlated with clinical and pathological parameters. Protein p16 was expressed in glottic LSCC of 15 patients (25.9 %). Statistically significant higher p16 overexpression was proven in non-smokers in comparison with smokers (75 % versus 18 %; p =0.003). Recurrent cancer was diagnosed in 8 patients (13.8 %), and all these tumors were p16 negative. Our study shows, that p16 expression in glottic LSCC especially in subgroup of non-smokers might be promising prognosticator of better clinical outcome in routine practice. The p16 status did not statistically correlate with cervical lymph node metastases or with grading and staging of cancers, respectively. The preliminary results suggest that p16 overexpression in glottic LSCC may identify patients at low risk of disease recurrence. However, the pathobiology of this tumor as well as predictive role of p16 expression in laryngeal cancer still remains to be better elucidated.
- MeSH
- dospělí MeSH
- glottis metabolismus patologie MeSH
- inhibitor p16 cyklin-dependentní kinasy metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru metabolismus mortalita patologie MeSH
- lymfatické metastázy MeSH
- míra přežití MeSH
- nádorové biomarkery metabolismus MeSH
- nádory hrtanu metabolismus mortalita patologie MeSH
- následné studie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- spinocelulární karcinom metabolismus mortalita sekundární MeSH
- staging nádorů MeSH
- stupeň nádoru MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- inhibitor p16 cyklin-dependentní kinasy MeSH
- nádorové biomarkery MeSH
The aim of the study was to investigate the role of high-risk human papillomavirus (HR-HPV) infection in the etiopathogenesis of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma in non-smoking and non-drinking patients (NSNDP). Twenty-four OSCCs and 22 OPSCCs were analyzed by immunohistochemistry for p16(INK4a) protein (p16) expression and by chromogene in situ hybridization (CISH) and polymerase chain reaction (PCR) for HR-HPV DNA presence. The series included 23 males and 23 females aged 35-93 years. p16 expression was seen in 7 out of 24 (29%) OSCCs and in 22 out of 22 (100%) OPSCCs. Using CISH, HR-HPV DNA was observed in 6 out of 24 (25%) OSCCs and in 21 out of 22 (95%) OPSCCs. HPV DNA was found in 3 out of 24 (13%) OSCCs and in 18 out of 22 (82%) OPSCCs using PCR. HPV 16 and 33 were detected in 16 and in two cases, respectively. Compared with OSCCs, OPSCCs more frequently showed basaloid morphology (p < 0.0001), lymph node involvement (p = 0.0063), diffuse p16 expression (p < 0.0001), HR-HPV DNA presence using both CISH and PCR (p < 0.0001; p < 0.0001), and better outcome. The sensitivity and specificity of p16 expression for HR-HPV DNA presence detected by CISH were 0.89 and 0.95, respectively, and 0.95 and 0.85 for PCR detected HPV DNA. The sensitivity and specificity of CISH for PCR detected presence of HPV DNA were 1.00 and 0.73, respectively. Our study is the first larger study analyzing OSCC and OPSCC in NSNDP. Our results indicate that unlike OSCC, a vast majority of OPSCCs may be associated with HR-HPV infection.
- MeSH
- DNA virů analýza MeSH
- dospělí MeSH
- hybridizace in situ MeSH
- imunohistochemie MeSH
- infekce papilomavirem komplikace MeSH
- inhibitor p16 cyklin-dependentní kinasy analýza biosyntéza MeSH
- kouření MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory orofaryngu etiologie patologie virologie MeSH
- nádory úst etiologie patologie virologie MeSH
- pití alkoholu MeSH
- polymerázová řetězová reakce MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- spinocelulární karcinom etiologie patologie virologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA virů MeSH
- inhibitor p16 cyklin-dependentní kinasy MeSH