Supervivencia de cirugía de rescate en carcinoma escamoso de orofaringe / Survival outcomes of salvage surgery in oropharyngeal squamous cell carcinoma

La recurrencia de carcinoma de células escamosas orofaríngeo (CCEOF) se asocia a mal pronóstico, particularmente en recurrencias en etapa avanzada. La cirugía en el contexto de rescate es más complicada por el tratamiento oncológico del tumor primario, por lo tanto, tiene un mayor riesgo de complicaciones y estadía hospitalaria. Sin embargo, la cirugía de rescate es la mejor oportunidad del paciente como tratamiento curativo y para supervivencia a largo plazo. La población de pacientes que reciben tratamiento para CCEOF ha cambiado en la última década, se ha reconocido que la incidencia de virus papiloma humano (VPH) asociado a CCEOF ha generado el gran aumento de CCEOF y el cambio asociado en las características de la población de pacientes, ahora los pacientes son más jóvenes y tienen menos comorbilidades. Con el aumento exponencial en la incidencia de CCEOF, la necesidad de cirugía de rescate en CCEOF podría verse en aumento. En vista del aumento de la incidencia de casos con carcinoma escamoso de orofaringe y su importante relación con el VPH, esta revisión se enfoca en la supervivencia tras cirugía de rescate con intención curativa y evaluar si con los avances en su tratamiento ha mejorado su pronóstico.

Recurrence of oropharyngeal squamous cell carcinoma (OPSCC) is associated with poor prognosis, particularly in advanced stage recurrences. Salvage surgery is complicated by previous oncological treatment of the primary tumor, therefore, it has a higher risk of complications and hospital stay. However, salvage surgery is the patient's best opportunity as a curative treatment and for long-term survival. The population of patients receiving treatment for OPSCC has changed in the last decade, it has been recognized that the incidence of human papilloma virus (HPV) associated OPSCC has generated an increase of OPSCC and changes in the epidemiology of the patient population, with younger patients and with less comorbidities. With the exponential increase in the incidence of OPSCC, the need for salvage surgery in OPSCC could increase in the future. In view of the increase in the incidence of cases with squamous oropharyngeal carcinoma and its relationship with HPV, this review focuses on survival after salvage surgery with curative intent and assessing whether the progress in its treatment has improved its prognosis.

Alterations in the expression and activity of extracellular matrix components in HPV-associated infections and diseases

Infection with human papillomaviruses is associated with a series of benign and malignant hyperproliferative diseases that impose a heavy burden on human populations. A subgroup of mucosal human papillomavirus types are associated with the majority of cervical cancers and a relevant fraction of vulvar, vaginal, anal, penile and head and neck carcinomas. Human papillomaviruses mediate cell transformation by the expression of two pleiotropic oncoproteins that alter major cellular regulatory pathways. However, these viruses are not complete carcinogens, and further alterations within the infected cells and in their microenvironment are necessary for tumor establishment and progression. Alterations in components of the extracellular matrix for instance, matrix metalloproteinases and some of their regulators such as tissue inhibitors of metalloproteinases, have been consistently reported in human papillomaviruses-associated diseases. Matrix metalloproteinases function by remodeling the extracellular matrix and alterations in their expression levels and/or activity are associated with pathological processes and clinical variables including local tumor invasion, metastasis, tumor relapse and overall patient prognosis and survival. In this review we present a summarized discussion on the current data concerning the impact of human papillomavirus infection on the activity and expression of extracellular matrix components. We further comment on the possibility of targeting extracellular matrix molecules in experimental treatment protocols.

p16INK 4a and Ki-67 expression in human papilloma virus-related head and neck mucosal lesions / Expresión de p16INK 4a y Ki-67 en las lesiones de cabeza y cuello relacionados con el virus del papilloma humano

Human papilloma virus (HPV) is postulated as a risk factor in the etiology of some specific mucosal pathologies in the head and neck regions. Despite the frequent use of p16INK4a as a surrogate marker for HPV-infection, there is still controversy with respect to its reliability. This study has been undertaken to assess the potential role of p16INK 4a and Ki-67 expression in HPV-related lesions. The study was conducted on 71 specimens of oral, tonsillar and laryngeal lesions which comprised 25 dysplasia and 46 papilloma specimens. Specimens were immunohistochemically stained for p16INK4A and Ki-67 proteins. HPV DNA was determined by one step multiplex polymerase chain reaction. HPV DNA was detected in 33.8% of all lesions. Tonsil and larynx lesions showed significant differences with oral lesions for HPV positivity (p<0.001). p16INK 4a over-expression was seen in 56.5% of papilloma and 60% of dysplasia specimens. HPV status showed a positive correlation with p16INK 4a expression in tonsillar dysplasias (p<0.001). p16INK 4a expression may have a value as a marker in high risk HPV induced dysplasias, but not in low risk infected lesions. The proliferation index is not related to HPV-induced lesions and may be evaluated as an independent marker in head and neck premalignant lesions.

El virus del papiloma humano (VPH) se postula como un factor de riesgo en la etiología de algunas patologías de la mucosa, específicas en las regiones de cabeza y cuello. A pesar de usar con frecuencia el p16INK4A como un marcador sustituto para la infección por VPH, todavía existe controversia con respecto a su fiabilidad. Este estudio se ha llevado a cabo para evaluar el papel potencial de la expresión de p16INK 4a y de Ki-67 en las lesiones relacionadas con el VPH. El estudio se realizó en 71 muestras de lesiones orales, tonsilares y laríngeas que comprendían 25 displasias y 46 especímenes de papiloma. Los especímenes fueron teñidos inmunohistoquímicamente para p16INK4a y Ki-67. El ADN del VPH se determinó mediante una PCR multiplex de un paso. ADN del VPH se detectó en el 33,8% de todas las lesiones. Las lesiones de la amígdala y laringe mostraron diferencias significativas con lesiones orales para la positividad de VPH (p <0,001). Sobre-expresión de p16INK 4a se observó en 56,5% de las muestras de papiloma y 60% de las muestras de displasia. El estatus del VPH mostró una correlación positiva con la expresión de p16INK4a en displasias tonsilares (p <0,001). La expresión de p16INK4a puede tener valor como marcador en las displasias inducidas por VPH de alto riesgo, pero no en las lesiones infectadas de bajo riesgo. El índice de proliferación no está relacionado con las lesiones inducidas por VPH y puede ser evaluado como un marcador independiente en las lesiones premalignas de la cabeza y del cuello.

Cáncer de cabeza y cuello asociado al virus papiloma humano: revisión de la literatura / Head and neck cancer associated with human papilloma virus: literature review

Oral cavity and oropharyngeal squamous cell carcinoma is the sixth most common cancer worldwide and human papillomavirus (VPH) is proposed as an etiologic risk factor. In our country there is no prevalence studies of this virus either in oral or oropharyngeal mucosa. This data would be useful at the moment of evaluating the risk in general population of developing head and neck cancer VPH related and also the impact that it could have the proved effective vaccines against VPH...

Impact of HPV infection on the development of head and neck cancer

Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is considered to be a distinct clinical entity with better prognosis than the classical tobacco- and alcohol-associated tumors. The increasing incidence of this neoplasia during the last decades highlights the need to better understand the role of HPV in the development of these cancers. Although the proportion of HNSCC attributed to HPV varies considerably according to anatomical site, overall approximately 25% of all HNSCC are HPV-DNA positive, and HPV-16 is by far the most prevalent type. In this review we discuss the existing evidence for a causal association between HPV infection and HNSCC at diverse anatomical head and neck subsites.

Human papilloma virus in head and neck squamous cell cancer

Epidemiologic and molecular evidences have established a strong link between high risk types of Human Papilloma Virus and a subgroup of Head and Neck Squamous Cell Carcinomas [HNSCC]. We evaluated the frequency of HPV positivity in HNSCC and its relationship to demographic and some risk factor variables in an open casecontrol study. Fourteen recently diagnosed patients with squamous cell cancer of oropharynx, hypopharynx and larynx aged 18-50 years were examined from 2008-2010 in Tabriz, Iran. HPV DNA was extracted from paraffin-embedded blocks of each patient's sample for PCR evaluation. Saliva samples of 94 control cancer-free subjects were collected for DNA analysis. Multivariable logistic regression method was used to calculate odds ratio for case-control comparisons. High risk HPV was detected in 6[42.8%] patients, and 6[5.3%] control subjects which was statistically significant [p<0.0001]. HPV-18 was the most frequent type both in the cases and controls. HPV-16 DNA was detected in two patients of the case group, but it was not detected in any of the controls. The relation between demographic and risk factor variables was not statistically significant. HPV infection has a significant impact on HNSCC. Despite HPV-16 stronger impact, HPV-18 is more likely to cause malignant degeneration in such cancers amongst some communities. It is vital to introduce and conduct immunization schedules in health care systems to protect communities to some extent

Prevalencia del VPH en el proceso de malignización de lesiones de vías aérodigestivas superiores / HPV prevalence on malignant lesion process of the upper aerodigestive tract

Los papilovirus o virus del papiloma son considerados el grupo más prevalente de virus causantes de tumores de cabeza y cuello asociados a la infección con virus del papiloma humano (VPH). Según revisiones sistemáticas en México y Colombia, la prevalencia de VPH en el proceso de malignización de lesiones de vías aerodigestivas superiores (VADS) se presenta con una incidencia en orofarìnge de 35,6 por ciento, en cavidad oral 23,5 por ciento y en laringe 24,0 por ciento. En ésta revisión también destacan los genotipos de VPH de bajo riesgo (VPH 31, 45, 6 y 11), los cuales inducen la aparición de algunas lesiones precancerosas. La falta de un diagnostico oportuno del VPH y de las lesiones que deriven de este virus, puede complicar el tratamiento del mismo. En cuanto a los métodos de su diagnóstico, se demuestra la efectividad del método PCR-RFLP como el punto de partida del monitoreo de la infección y su progresión a cáncer. Estos métodos pueden permitir comprender la virulencia del mismo y contribuir a la disminución de las tasas de incidencia a causa de las imprecisiones de diagnostico clínico por metodologías convencionales ya que dificultan la detección precoz del cáncer de las vías aerodigestivas superiores.

Papilovirus or papillomaviruses are considered the most prevalent group of viruses that cause tumors of head and neck associated with infection with human papilloma virus (HPV). According to systematic reviews in Mexico and Colombia, the prevalence of HPV in the process of malignant lesions of the upper aerodigestive tract, can be shown with a clinical prevalence of 35,6 percent in oropharynx, 23.5 percent in oral cavity and 24.0 percent in larynx. This review highlights the genotypes of low-risk HPV (HPV 31, 45, 6 and 11), which induce the appearance of precancerous lesions. It demonstrates the effectiveness of PCR-RFLP method as a starting point for the monitoring of infection and progression to cancer this method can facilitate understanding of its virulence activity and contribute to reduced incidence rates because of the inaccuracies of clinical diagnosis by conventional methods that hinder the early detection of cancer of upper aerodigestive tract.

El virus del papiloma humano como factor pronóstico en pacientes con carcinoma epidermoide de cabeza y cuello / Human papilloma virus in patients with epidermoid head and neck carcinoma: a prognostic factor

Introducción: Los tres principales factores pronóstico en pacientes con carcinoma epidermoide de cabeza y cuello (CECyC) son tamaño del tumor, estado histológico ganglionar y origen del tumor. Se ha reconocido al virus del papiloma humano, sobre todo la variedad 16 (VPH-16), como factor pronóstico, sin embargo, resulta controversial que los pacientes VPH+ tengan mejor supervivencia que los VPH−. El objetivo del presente es conocer si la infección por VPH tiene valor pronóstico en pacientes con CECyC. Material y métodos: Evaluación retrospectiva de pacientes con CECyC. Se analizó supervivencia, localización tumoral, estado general (ECOG), tipo de tratamiento y asociación a VPH identificado por PCR en tejido tumoral. Análisis descriptivo de frecuencias simples, medidas de tendencia central y dispersión, de acuerdo con el tipo de variables. Análisis descriptivo para supervivencia con Kaplan-Meier y regresión de Cox, con intervalo de confianza de 95%. Resultados: Se incluyeron 179 pacientes, 119 (66.5%) hombres; promedio de edad de 64 años; 34% de los tumores se localizó en cavidad oral y 33% en laringe. Factores asociados con supervivencia: ECOG (RR = 11.3, 2.6-48), estadio clínico (RR = 7.8, 1.7-34), edad mayor a 70 años (RR = 3.5, 1.4-8.5) y tratamiento no quirúrgico (RR = 2.3, 1.4-3.8). La mediana de supervivencia para pacientes con VPH-16 fue de 22 meses versus 28 meses de quienes tuvieron otros tipos virales. La infección por VPH no se asoció con el pronóstico. Conclusiones: El ECOG en el momento del diagnóstico y la etapa clínica fueron los factores pronóstico más importantes en esta serie; el VPH no mostró valor pronóstico.

BACKGROUND: The three most important prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC) are tumor size, nodular histological condition and tumor origin. Recently, human papilloma virus (HPV), particularly HPV-16, has been acknowledged as a prognostic factor. HPV+ patients have better survival than HPV-. This has created a controversy because other factors may influence the prognosis. The objective of this study was to investigate whether HPV has prognostic value in patients with HNSCC. METHODS: We carried out a retrospective evaluation of patients with HNSCC and the following variables were analyzed: survival, tumor location, stage, general condition according to Eastern Cooperative Oncology Group (ECOG) status, treatment and HPV association identified by PCR. We used a descriptive analysis of simple frequencies and central tendency and dispersion measures according to the type of variables. We used descriptive analysis for overall survival with Kaplan- Meier and Cox regression with 95% confidence interval. RESULTS: There were 179 patients included: 119 (66.5%) were male. Average age of patients was 64 years; 34% of the tumors were located in the oral cavity and 33% were located in the larynx. Factors associated with survival were ECOG (RR = 11.3; 2.6-48), clinical stage (RR = 7.8; 1.7-34), age >70 years (RR = 3.5, 1.4-8.5) and nonsurgical treatment (RR = 2.3; 1.4-3.8). Average overall survival for patients with HPV16 was 22 months vs. 28 months in those with other types of viruses. HPV infection was not associated with the prognosis in this series. CONCLUSIONS: ECOG at the time of the diagnosis and clinical stage were the most significant prognostic factors in this series. HPV did not show any prognostic value.

Polymerase chain reaction; detection of human papilloma virus [HPV] type - 16 and 18 infection in laryngeal and oral squamous cell carcinoma in southern Iran

One fifth of cancers world wide are associated with viral infection. Epidemiologic and biomolecular evidence suggested that Human Papilloma Virus [HPV] infection may be associated with the development of head and neck cancer. [1] To clarify the role of HPV infection in head and neck cancers. [2] To evaluate the presence of HPV DNA in laryngeal and oral squamous cell carcinoma in southern Iran and comparison of results with studies in other regions Department of Otolaryngology-Head and Neck Surgery, Khallili Hospital, Shiraz Medical University Iran From 2003 to 2006. Eighty three [83] patients with Squamous Cell Carcinoma [SCC] of the larynx, 40 patients with benign mucosal lesion of the larynx [control], 47 patients with SCC of oral cavity and 10 patients with benign oral lesion were studied for the presence, of HPV DNA by Polymerase Chain Reaction [PCR]. None of the laryngeal SCCs or control group was positive for HPV DNA. Only 3/47 specimens from oral SCC were positive for HPV DNA. Oral control group was negative for HPV DNA. The present work suggests that HPV infection has not important role in carcinogenesis of laryngeal or oral SCC in southern Iran. However a multi center case-control study is needed to clarify this association

Epstein-Barr virus in head and neck squamous cell carcinoma

We compared 50 patients with head and neck squamous cell carcinomas [cases] and 45 matched healthy controls. Biopsy specimens were taken from tumours and normal tissue of the cases and controls respectively and serial paraffin embedded sections were processed to detect Epstein-Barr [EB] viral antigen. We found EB viral proteins in 38% of cases and none in controls, which suggests a positive correlation. Serum samples were also tested for the presence of EB virus IgG by ELISA for comparison with immunohistochemical findings. Patients with positive immunohistochemical staining results had significantly higher mean antibody titres compared with those with negative results. ELISA may be useful in determining the etiology of head and neck cancers, but the results are not unequivocally reliable