The accumulation of human papillomavirus type 16 (HPV-16)-specific RNAs in tissue sections from biopsies of patients with genital precancers was studied by in situ hybridization with single-stranded 35S-labeled RNA. These analyses revealed that the most abundant early-region RNAs were derived from the E4 and E5 open reading frames (ORFs). RNAs homologous to the E6/E7 ORFs were also detected, whereas RNAs homologous to the intervening E1 ORF were not. This suggests that the E4 and E5 mRNAs are derived by splicing to the upstream E6/E7 ORFs, consistent with studies of HPV-11 in condylomata (L. T. Chow et al., Cancer Cells (Cold Spring Harbor) 5:55-72, 1987). Abundant RNAs homologous to the 5' portion of L1 were also detected. These RNAs were localized to the apical strata of the epithelium. HPV-16 RNAs accumulated in discrete regions of these lesions, and when present were most abundant in the upper cell layers of the precancerous epithelium. RNAs homologous to early ORFs were also detected in some germinal cells within the basal layer of the epithelium.
In this study we determined the frequency of association of human papillomavirus (HPV) and laryngeal carcinomas and investigated the possibility that HPV may be associated with larger or more aggressive tumors. Laryngeal squamous cell carcinomas from 40 patients who did not have preexisting papillomas by clinical history were retrieved from formalin-fixed, paraffin-embedded blocks and analyzed for HPV. Twenty-two cases were tumors of the true vocal folds, and 18 were supraglottic. Clinical follow-up was available for 25 patients. We used the polymerase chain reaction (PCR) with the "hot start" modification and consensus primers that can detect over 30 distinct HPV types. Three of the 40 patients (8%) had detectable HPV DNA. These 3 patients did not have unusual age demographics and were smokers. All but 1 of the 22 HPV-negative patients who were questioned were also smokers. We compared the outcomes for large (4 cm or greater) HPV-positive and -negative tumors. Six of the 40 tumors were 4 cm or greater and involved contiguous structures. Two of these 6 were HPV-positive, and these patients died of disease after 3 and 16 months, respectively. Of the 4 HPV-negative patients with tumors greater than 4 cm, 3 are disease-free at 41, 42, and 3 months, respectively, and 1 was lost to follow-up. The third HPV-positive patient had a tumor less than 1 cm, and is disease-free after 38 months. While the number of HPV-positive cases is too small for definitive conclusions, it is possible that for large tumors the presence of HPV DNA may portend a worse prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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