Richard W. Todd

Human papillomavirus (HPV) type 16-specific CD8+ T cell responses in women with high grade vulvar intraepithelial neoplasia†

Human papillomavirus (HPV)‐associated vulvar intraepithelial neoplasia (VIN) has serious sequelae for the sufferer. Current treatments are associated with poor response and high relapse rates. The development of HPV‐specific T cell immunotherapies offers a new approach to treatment. This will require a detailed understanding of the spectrum of T cell responses induced by HPV antigens, and how effectively viral antigens can be accessed by the immune system. We have investigated the frequency and spectrum of HPV16‐specific CD8+ T cell responses to three HPV16 antigens in 9 women with high grade VIN (VIN3). CD4‐depleted populations of responder cells were screened against overlapping 30–35mer peptides covering the sequences of HPV16 E6, E7 and E4 using ELISPOT assays of IFN‐γ release. We demonstrated CD8+ T cell reactivity to one or more of the proteins in 6 of 9 patient samples. All 6 of these responders recognised peptides covering the E7 protein, 3 of 9 women responded to E6 peptides, but no reactivity was seen to E4. Our results suggest that HPV16‐specific cytotoxic T cells (CTLs) are relatively common in women with persistent VIN3. The HPV‐specific CTL response, however, seems to be ineffective. There is some evidence that there are problems associated with the processing and presentation of HPV antigens by the infected vulvar epithelium. It will be crucial to address this in the design of any T cell based therapy for HPV‐associated VIN and vulval cancer.

Medical management of vulvar intraepithelial neoplasia.

Objective. To determine which nonsurgical treatments have been assessed for the treatment of vulvar intraepithelial neoplasia (VIN) and what the outcomes of such treatment might be. Materials and Methods. The English literature over the last 25 years was searched on Medline. Results. A wide variety of nonsurgical treatments was identified and the outcomes were very similar. These treatments showed responses rates varying between 10% and 60%. Responses were poorly defined, however, and few if any studies had large enough subject numbers or long enough follow-up to allow robust conclusions. Conclusions. Although VIN is a condition in which there would seem to be a pressing need for nonsurgical interventions, none of the nonsurgical treatments reviewed resulted in optimal outcomes. No one treatment seemed to be superior. There is a need for consensus on how outcomes are measured and a move toward large well-constructed studies is recommended. Because VIN is uncommon, there is a strong case for establishing research collaboratives.

Primary uterine osteosarcoma presenting synchronously with bilateral breast carcinomas

Primary uterine sarcomas are infrequent neoplasms and most commonly leiomyosarcomas or endometrial stromal sarcomas. We report a rare case of primary uterine osteosarcoma discovered in a woman in her 60s following staging CT imaging for bilateral breast carcinomas. Examination of the subsequent hysterectomy specimen showed a tumour composed of malignant spindle cells and osteoclast-like giant cells associated with osteoid and neoplastic bone, in keeping with primary uterine osteosarcoma. Distinction of osteosarcoma from the more common carcinosarcoma is important due to the worse prognosis impacting on treatment decisions. In addition, synchronous presentation of this unusual tumour with bilateral breast carcinomas raises the possibility of a mutual genetic pathogenesis.

Sesiones clínicas multidisciplinarias de correlación clínico-patológica colposcópica: revisión de la actividad

Objetivo. Las sesiones clínicas multidisciplinarias de correlación clínico‐patológica colposcópica se consideran un aspecto importante de la garantía de calidad colposcópica y a menudo son uno de los centros de atención en las evaluaciones externas de garantía de calidad colposcópica. A pesar de ello, hay pocos datos sobre estas sesiones en las que se detalle la actividad realizada o se aporte una referencia para las auditorías. Material y métodos. Se llevó a cabo un análisis retrospectivo de las sesiones clínicas de correlación clínico‐patológica celebradas durante un periodo de 3 años (2004‐2006) en el University Hospital of North Staffordshire. Resultados. Se celebraron un total de 65 reuniones a intervalos de 2 a 4 semanas. En todas ellas hubo representantes de citología, anatomía patológica y colposcopia. Se incluyeron en los programas de presentación 518 casos, de los que 475 fueron presentados y comentados, lo cual corresponde a un 6,6% del total de visitas de pacientes en la clínica de colposcopia durante el período de estudio. Las principales indicaciones para el análisis de los casos en las sesiones fueron las siguientes: discrepancia de citología/histología (35%), discrepancia de citología/colposcopia (10%), dilema en cuanto al manejo (25%) y revisión de cáncer invasivo (18%). Una pequeña parte de los casos programados para las sesiones (8%) no llegaron a comentarse debido a problemas administrativos. Estos problemas se debieron a la calidad de la documentación e inconsistencias en el registro de los resultados, las conclusiones y los planes de manejo. Conclusiones. Las sesiones clínicas multidisciplinarias clínico‐ patológicas colposcópicas aportan una fuente de datos útil para registrar y analizar ámbitos de especial dificultad en el manejo clínico de las mujeres con citología cervical anormal. Sin embargo, estas sesiones requieren tiempo y esfuerzo, tanto en lo relativo a la dedicación del personal como en cuanto a la preparación. Deberán desarrollarse directrices nacionales para orientar a los clínicos sobre la frecuencia y las normas de calidad exigidas en estas reuniones. ▪