SUMMARYThe DNA of distinct human papillomaviruses (HPVs) is regularly detected in the majority of human cervical carcinomas. In contrast to benign HPV-induced genital lesions, where the viral genomes are exclusively present as episomes, in cervical carcinomas HPV type 16 (HPV16) DNA was found to be integrated into the host DNA. In order to determine the physical state and expression of HPV DNA sequences at different stages of tumour development, we analysed a series of cervical lesions (mild, moderate and severe dysplasia and carcinoma in situ) that are considered precursors of carcinomas of the cervix. In 66.6~ (18 of 27) of the tumours, HPV16 DNA was present. While in mild dysplasias only episomal HPV genomes were found, in all higher grade lesions integration of the viral DNA was detected. There was a close correlation between the episomal state and the expression of the HPV 16 genomes : in 15 cases harbouring episomal HPVI6 DNA (seven of which also contained integrated genomes) viral transcripts were present. We conclude that integration of HPV genomes takes place very early in cervical cancer development. In addition, the episomal state of the viral DNA depends on viral gene expression. The same conclusion, however, is not applicable in those lesions (three severe dysplasias) containing exclusively integrated HPV16 DNA. Thus, HPV16 DNA can persist in an integrated state without recognizable transcriptional activity. These results point to HPVI6 as one potential prerequisite for the first steps in the multistage development of human cervical cancer.

In light of recent endoscopic techniques the current value of double-contrast pharyngography (DCP) and of CT for detection and staging of hypo-, oropharyngeal, and supraglottic tumors is evaluated. The DCP of 151 patients and CT obtained from 99 of these patients were retrospectively analyzed in a double-blinded manner. We used a standard protocol which comprised all relevant anatomical subregions. Results were compared with direct microlaryngoscopy (DL), indirect laryngoscopy (IL), and post-operative histopathological findings. Sensitivity and specificity of DCP was 75.0 % and 86.7 %, respectively. The DCP and IL techniques together yielded a higher sensitivity (96.7 %) than each method separately. Sensitivity and specificity of CT was 87.5 and 100 %, respectively. In 74.7 % CT provided correct staging. Subregional analysis revealed that the results of DCP and CT depend highly on the localization of the tumor. Our results indicate that DCP represents an important screening method for diagnosing hypo-, oropharyngeal, and supraglottic tumors to complete IL and DL. We show that CT is a reliable method for preoperative staging, although small superficial tumors may occasionally be missed by this method.

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