RESUMEN
HYPOTHESIS: Assessment of the prevalence and type distribution of human papillomavirus (HPV) in squamous cell carcinomas (SCC) of the cervix across India was undertaken to estimate the impact of available prophylactic HPV-L1 vaccines in the country and to find out additional types that might be needed to be incorporated in second-generation vaccines. METHODS: High-risk (HR) HPVs were genotyped from 667 histopathologically confirmed cases of SCC from 6 different centers representing 4 regions across India: Advanced Centre for Treatment, Research and Education in Cancer, Mumbai; All India Institute of Medical Sciences, New Delhi; Cancer Foundation of India, Kolkata; Christian Medical College, Vellore; Kidwai Memorial Institute of Oncology, Bangalore; and Regional Cancer Center, Thiruvananthapuram. Human papillomaviruses in tumor biopsies were analyzed by Xcytonscreen HPV based on PGMY09/11 multiplex polymerase chain reaction and reverse dot blot assay. RESULTS: Overall viral prevalence across India was not different; 92.1% of 667 cases harbored HPV; 8% were negative. Infection with single HR type was seen in 86.8%: predominant types being HPV-16 followed by HPV-18, -45, -73, -31, -56, -52, -58, -59, -33, -68, -51, -35, -26, and -39. Human papillomavirus types 16/18-positive fraction formed 79.6%; other types comprised 12.4%. CONCLUSIONS: Prophylactic HPV-16/18-L1 vaccines would provide greater than 75% protection against SCC in India. Ranking and frequencies of non-16/18 types were different from earlier reports. Hence, considering the possibility of promotion of persistence of nonvaccine types in the vaccinees due to original antigenic sin and the lack of organized screening programs in India, a broad-based vaccine approach would be appropriate.
Asunto(s)
Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/virología , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , ADN Viral/análisis , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Humanos , Inmunohistoquímica , India/epidemiología , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Reacción en Cadena de la Polimerasa , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/patología , Prevalencia , Medición de Riesgo , Neoplasias del Cuello Uterino/patología , Frotis VaginalRESUMEN
AIMS: Cisplatin-based chemotherapy with radiotherapy is currently the standard treatment for locally advanced carcinoma of the cervix. Recent studies have shown a better response with the addition of newer chemotherapeutic agents. The aim of this phase I study was to establish the maximum tolerated dose (MTD) of paclitaxel in combination with cisplatin as a radiosensitiser along with radiation therapy in the treatment of carcinoma of the cervix and to analyse the toxicity profile of the combination regimen. MATERIALS AND METHODS: In total, 21 newly diagnosed patients with squamous cell carcinoma of the cervix, International Federation of Gynecology and Obstetrics stage IB to IIIB were included in this trial. All patients received external beam radiation therapy to the pelvis (50 Gy in 25 fractions) delivered by conventional four-field box technique followed by low dose rate brachytherapy. Concurrent chemotherapy was administered with weekly cisplatin (30 mg/m(2)) and an escalating dose of weekly paclitaxel starting at 10 mg/m(2) up to 50 mg/m(2) (according to the modified Fibonacci series). RESULTS: The MTD of weekly paclitaxel was found to be 40 mg/m(2). The dose-limiting toxicity that occurred in our patients at a dose of 50 mg/m(2) weekly paclitaxel was grade 3 proctitis and vaginitis. CONCLUSION: In this phase I trial of concurrent radiation and combination chemotherapy with weekly paclitaxel and cisplatin (30 mg/m(2)/week), the MTD of paclitaxel was found to be 40 mg/m(2). This combination was feasible, with an acceptable toxicity profile.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia/efectos adversos , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Dosis Máxima Tolerada , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Radioterapia/efectos adversos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patologíaRESUMEN
Human papilloma virus is a causative factor in the etiology of cervical cancer with HPV16 being the most prevalent genotype associated with it. Intratype variations in oncogenic E6/E7 and capsid L1 proteins of HPV 16 besides being of phylogenetic importance, are associated with risk of viral persistence and progression. The objective of this multicentric study was to identify HPV-16 E6, E7 and L1 variants prevalent in India and their possible biological effects. Squamous cell cervical cancer biopsies were collected from 6 centres in India and examined for the presence of HPV 16. Variants of HPV-16 were characterized by full length sequence analysis of L1, E6 and E7 genes in 412 samples. Similar distribution of the variants was seen from the different centres/regions, with the European variant E350G being the most prevalent (58%), followed by American Asian variant (11.4%). Fifty six changes were seen in E6 region, 31 being nonsynonymous. The most frequent being L83V (72.3%), Q14H (13.1%) and H78Y (12.1%). Twenty-nine alterations were seen in E7 region, with 12 being nonsynonymous. The most frequent being F57V (9%). L1 region showed 204 changes, of which 67 were nonsynonymous. The most frequent being 448insS (100%), and 465delD (100%), H228D (94%), T292A (85%). The identified variants some new and some already reported can disrupt pentamer formation, transcriptional regulation of the virus, L1 protein interface interaction, B and T cell epitopes, p53 degradation, and thus their distribution is important for development of HPV diagnostics, vaccine, and for therapeutic purpose.
Asunto(s)
Proteínas de la Cápside/genética , Variación Genética , Papillomavirus Humano 16/genética , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/genética , Proteínas Represoras/genética , Neoplasias del Cuello Uterino/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virología , Femenino , Papillomavirus Humano 16/clasificación , Humanos , India , Persona de Mediana Edad , Proteínas E7 de Papillomavirus , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virologíaRESUMEN
Capillary haemangiomas rarely occur in the auditory canal and have mainly been managed with surgical excision or kept on close follow up for development of symptoms. Radiotherapy, as a treatment method, has not been reported previously in the published work. We describe a study of a capillary haemangioma in the auditory canal of a 26-year-old woman who presented with bleeding. She was treated with radiotherapy, after the lesion was found to be unsuitable for surgery and embolization. The patient remains well 5 years after completion of treatment.