Hpv und p16
In addition to tobacco and alcohol abuse, certain viruses have been associated with squamous cell carcinoma SCC of the head and neck, causing alterations in DNA. It has been demonstrated that the human papillomavirus HPV type 16, a subtype of the human papillomavirus, is present in the oropharyngeal carcinomas of non-smokers patients inclusive.
HPV-infected cells express some viral proteins encoded by genes called E6 and E7, and can inactivate p53 protein and the retinoblastoma-type protein RBP involved in the regulation hpv und p16 proliferation and cell death. Materials and method. We present an immunohistochemical study conducted to identify significant tumour markers in tonsillar SCC.
We present the statistically significant correlations between the presence of immunohistochemical markers and studied local recurrence, lymph node recurrence and risk of a second cancer in the aerodigestive upper tract.
Hpv und p16 demonstration of HPV in tonsillar tumour tissue requires in situ hybridization or polymerase chain reaction PCR for the evidence of viral genome included into the host cell.
Studiile au demonstrat ca femeile si barbatii activi pe plan sexual sunt expusi la acest virus la un moment dat in viata.
The practical implications of an etiologic role of HPV in head and neck cancer generally and in tonsillar SCC in particular remains in question and is in relate with prognosis, treatment hpv und p16 prevention. În afară de consumul de tutun şi abuzul de alcool, anumite virusuri au fost asociate cu carcinomul cu celule scuamoase CCS al capului şi gâtului, cauzând alterări la nivelul ADN-ului. Este dovedit că virusul papiloma uman HPVtipul 16, este prezent la nivelul carcinoamelor orofaringiene inclusiv în cazul nefumătorilor.
Celulele infectate cu HPV exprimă unele proteine virale codate de genele denumite E6 şi E7 şi pot inactiva proteina p53 şi proteina de tip retinoblastom RBP implicate în reglarea proliferării şi morţii celulare.
6. Tumour Suppressor Genes (Retinoblastoma and the two hit hypothesis, p53)
Materiale şi metodă. Prezentăm un studiu imunohistochimic realizat cu scopul de a identifica markeri tumorali semnificativi în CCS de amigdală.
Prezentăm corelaţiile semnificative statistic între prezenţa markerilor imunohistochimici şi recurenţa locală, recurenţa nodulilor limfatici şi riscul apariţiei unui al doilea cancer în tractul aerodigestiv superior.
Hpv und p16 în evidenţă a HPV-ului în ţesutul tumoral amigdalian necesită hibridizare in situ şi reacţie de polimerizare în lanţ Hpv und p16 pentru punerea în evidenţă a genomului viral conţinut în celula-gazdă. Implicaţiile practice ale unui rol etiologic al HPV-ului în cancerele de cap şi gât, în general, şi în CCS de amigdală, în particular, reprezintă un subiect în dezbatere, fiind în relaţie cu prognosticul, tratamentul şi prevenţia acestor tipuri de cancere.
Acesta sta la baza majoritatii neoplaziilor cervicale, dar si hpv und p16 procent mai scazut al celor vulvare, anale si din zona gatului. Virusul Papilloma uman se infiltreaza in mucoase si in piele, transmitandu-se pe cale sexulala exclusiv, de multe ori fara ca partenerii sa fie instiintati de existenta lui. Aceasta infectie nu prezinta simptomatologie asociata.
Cuvinte cheie carcinomul cu celule scuamoase de amigdală CCS HPV markeri tumorali Introduction The tonsillar squamous cell carcinoma SCC is becoming a public health problem because of its rising incidence in the last 20 years, in contrast to the decreasing incidence of carcinomas in other subsites of head and neck associated to the reduced prevalence of smoking. These tumours of oral cavity, oropharynx, larynx, hypopharynx and sinonasal region are linked by common characteristics, including a male predominant appearance in the 5th-6th decade of life, an important etiological link with tobacco, alcohol use or hpv und p16 nut chewing, and a histopathological resemblance 1.
Data regarding the epidemiology revealed that in Romania the oropharyngeal cancer represents 2. In France, during the last 30 years, the mortality in oral and oropharyngeal cancer increased by three hpv und p16 1. As in hpv und p16 cancers, the oropharyngeal infection with HPV hpv und p16 a sexually transmitted disease which involves some particularities of sexual behaviour: a large number of vaginal sex partners, oral and anal sex.
The recent increasing of OPSCC incidence may reflect the social changes regarding sexual behaviour in the modern world 6. The anatomical sites preferred by HPV in oropharynx are the tonsils and the tongue, because of the unique presence of transitional mucosa in oropharynx hpv und p16 particular in ca un vierme tissue, which presents important histological similarities with the cervical mucosa.
Tonsillar epithelium invagination may favour virus capture and viermi și preparate pentru giardia pentru adulți its access to basal cells the only dividing cells in the epithelium. The tonsillar tissue could be a reservoir for HPV in the upper aero digestive tract.
We had two premises for our study on tonsillar cancers. The second consists in the fact that mutagens such as tobacco, alcohol and HPV viral oncogenes E6 and E7 induce dysfunctions of two major hpv und p16 of cellular cycle, which involves the p53 and RBP tumoral suppressor genes 2.
Materials and method We made an immunohistochemical retrospective study between andaiming to identify any correlations between tumoral markers and the evolution and prognosis in hpv und p16 SCC. Materials We studied 52 cases of patients diagnosed with tonsillar SCC. We had a first group Group I with 25 cases, where the positive diagnose was made by biopsy hpv und p16 these patients had radiotherapy as first curative method of treatment. We had a second group Group II with 27 cases, where the positive diagnose was made on surgical specimens and these patients had surgery as the first curative method of treatment.
The two groups were similar regarding age and gender distribution. The dilutions and markers specifications are revealed in Table 1. We also studied lymphocyte populations CD4, CD8, and populations of dendritic cells in tumour tissue. Table 1.
The dilutions and markers specifications For the immunohistochemical identification hpv und p16 tumoral antigens we used the three-stadial indirect method Avidine-Biotine-Peroxidase ABPafter Hsu and colab.
Results The gender repartition of cases was: 47 male cases and 5 female cases. The age repartition of cases was: two cases between years old, 14 cases between years old, 21 cases between years old, 10 cases between years old, and five cases between years old.
The correlation coefficient between the two sets of data, corresponding to Group I and Group II, was 0. In both groups, we had 48 smoker patients, representing The patients who were both smokers and alcohol consumers represented We studied the tumoral markers on 52 cases of squamous cell carcinoma.
Thirty-eight cases were well differentiated carcinoma and 14 cases were medium differentiated carcinoma. We present the results, that we considered immunohistochemically valid and statistically hpv und p16 Table 2. Table 2. The distribution of tumoral markers in hpv und p16 of SCC studied We realised a correlation between the presence of the tumoral marker of a certain type positive and slowly positive results and the post-therapeutic evolution — local recurrence, nodal relapse, the occurrence of second cancers in upper aerodigestive upper ways and distance metastases.
We hpv und p16 had patients who had more than one recurrence in the same time. Our purpose was to identify the correlations between markers of evolution and prognosis in tonsillar SCC.
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Our results indicate p53 protein and RBP protein as tumoral markers of unfavourable prognosis for post-therapeutic evolution in tonsillar SCC. For TGFa, we can make a correlation between its level in tumoral tissue and the risk of loco-regional relapse. For the HPV identification in tumoral tissue, we used the identification of capsid p16 protein, so we cannot make definitive conclusions referring at the presence or absence of HPV in the tumoral tissue for patients with tonsillar SCC.
But we realised a correlation between the presence of HPV and the type of post-therapeutic evolution Peritoneal cancer relapse Figure 1. The presence of RBP protein 48 positive and slowly positive cases was associated with local recurrence in 29 cases The presence of TGF protein 41 positive and slowly positive cases was associated with local recurrence in 18 cases The presence of HPV capsid protein 14 positive cases was hpv und p16 with local recurrence in nine cases Figure 6.
Tumoral markers in evolution of tonsillar SCC result of our retrospective study From our data, we can certify as prognostic factors in tonsillar SCC: T stage, N stage, performing or not an elective type of clinical negative neck N0, type of neck dissection, the total dose of radiotherapy. We cannot make statistical significant conclusions referring to the HPV presence in tumoral tissue in tonsillar SCC and long-term prognosis.
Demonstrating the presence of HPV in tonsillar tumoral tissue imposes hybridisation in situ or polymerase chain reaction PCR. Discussion Slaughter hpv und p16 al. They explained the greater risk for multiple primary cancers 8. Tobacco and alcohol abuse increase the risk for a second cancer development in patients with oropharyngeal SCC.
Tobacco hpv und p16 alcohol abuse are associated with mutations of the p53 protein in patients with OFSCC, being important factors in the molecular progression through carcinogenesis 9. Many clinical studies searched for the p53 protein mutations on surgical specimens from patients with OFSCC.
The patients with surgical positive edges for p53 protein mutations have a higher risk of local relapse P53 protein mutations are involved in the loco-regional failure at OFSCC tonsillar with curative radiotherapy The HPV 16 DNA hpv warts virus identified only in primary tumour cells and in their metastases in similar manner with cervical cancer 3.
The presence of HPV 16 genome was revealed by polymerase chain reaction PCR or the method of hybridisation in situ, which certified the presence of viral genome included in host cell genome It is necessary to make a study on HPV tonsillar infection in non-smokers and non-alcoholic consumers. Our method for HPV identification was immunohistochemistry for p16 protein, which is a specific hpv und p16 protein of HPV 16 type, so we cannot certify the presence of HPV genome in all specimens studied.
We were in the situation of the unavailability of the in situ hybridization kits or polymerase chain reaction for HPV 16 type during the study. We have to mention the high cost for identifying viral markers. Clinical stadialization represents the primary guide to choose the therapeutic modality, but it is a limited guide. We expected the genetic analysis to be the method of future, meaning the identification of markers for prevention, therapy and good hpv und p16.
Recent studies showed an inverse correlation between the presence of HPV hpv und p16 p53 protein mutations. The HPV-positive tumors have genetic alterations associated with a better answer to chemotherapy and with an improved radio-sensitivity. The immune response of the patient is better, because of the immune stimulation realised by viral antigens.
Informatii generale despre virusul HPV
The younger age with less comorbidities may contribute to a better prognosis Prophylactic vaccination is not efficient in already diagnosed infections and in malignant lesions, so it is necessary to study the efficiency of therapeutic HPV vaccination in the treatment of HPV-associated cancer 1.
We found in literature premises for the therapeutic vaccination in HPV-induced cancers, where this type of vaccine induced a cytolytic immune response in cells which express it 5. It is necessary to study the carriage of HPV in apparently normal tonsillar tissue, to have screening programmes and to select the patients at risk for OFSCC Conclusions The prognosis in tonsillar Hpv und p16 is mediocre, due to local recurrence, nodal relapse, the occurrence of second cancers in upper aerodigestive upper ways 17 and to distance metastases.
Oxiuros na gravidez our data, we can certify as prognostic factors in tonsillar SCC: T stage, N stage, performing or not an elective type of clinic negative neck N0, type of neck dissection and total dose of radiotherapy.
We cannot draw significant conclusions referring to the HPV presence in tumoral tissue in tonsillar SCC and regarding the prognosis signification of the HPV presence in the tumoral tissue. The presence of HPV 16 can be considered a positive prognostic factor for disease-free survival and hpv und p16 healing, but the use as a predictive marker has not yet been proven.
The best treatment against cancer is prevention, especially in malignancies where the main pathogen agent is known, and we are talking here about smoking, alcohol consume and a safe sexual behaviour.
Ethical approval: All authors hereby declare that all experiments have been examined and approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the Declaration of Helsinki.
She has done an accurate immunohistochemical examination of paraffin-embedded specimens. Conflict of interests: The authors declare no conflict of interests. Acta Otorhinolaryngol Italica. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck.
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