HPV-16 infection may be a risk factor for squamous-cell carcinoma of the head and neck.

Background:The hypoxia marker pimonidazole is a candidate biomarker of cancer aggressiveness. We investigated the transcriptional programme associated with pimonidazole staining in prostate cancer.Methods:Index tumour biopsies were taken by image guidance from an investigation cohort of 52 patients, where 43 patients received pimonidazole before prostatectomy. Biopsy location within the index tumour was verified for 46 (88%) patients, who were included for gene expression profiling and immunohistochemistry. Two independent cohorts of 59 and 281 patients were used for validation.Results:Expression of genes in proliferation, DNA repair and hypoxia response was a major part of the transcriptional programme associated with pimonidazole staining. A signature of 32 essential genes was constructed and showed positive correlation to Ki67 staining, confirming the increased proliferation in hypoxic tumours as suggested from the gene data. Positive correlations were also found to tumour stage and lymph node status, but not to blood prostate-specific antigen level, consistent with the findings for pimonidazole staining. The association with aggressiveness was confirmed in validation cohorts, where the signature correlated with Gleason score and had independent prognostic impact, respectively.Conclusions:Pimonidazole staining reflects an aggressive hypoxic phenotype of prostate cancer characterised by upregulation of proliferation, DNA repair and hypoxia response genes.

The oncogenic potential of the human papillomavirus (HPV) early genes E6 and E7 is well established and a source of interest with regard to HPV testing for cervical carcinoma. Here we present a study performed with 204 histologically confirmed invasive cervical squamous cell carcinomas (SCCs) in which we evaluated the HPV E6 and E7 mRNA detection assay PreTect HPV-Proofer for detection of high-risk HPV types 16, 18, 31, 33, and 45. For further evaluation, detection of E6 and E7 mRNA from HPV types 35, 52, and 58 by real-time multiplex nucleic acid sequence-based amplification was also included. For comparison and to assess the overall prevalence of various HPV types, samples were also tested for HPV DNA by both consensus and type-specific PCR, reverse line blotting, sequencing, and in situ hybridization. The overall prevalence of HPV was 97%. HPV E6 and E7 transcripts were detected in 188 of 204 (92%) biopsy specimens, of which 181 contained one of the following HPV types: 16, 18, 31, 33, or 45. Consensus PCR and type-specific PCR detected HPV in 187 of 204 and 188 of 204 (92%) specimens, respectively. In conclusion, this study verifies the presence of HPV E6 and E7 mRNA in SCCs and demonstrates that HPV infections among Norwegian women with SCCs are limited mainly to the five high-risk types, 16, 18, 31, 33, and 45. This, together with the fact that PreTect HPV-Proofer detects the HPV oncogenic transcripts, suggests that the assay is a valuable approach in the field of HPV detection in cervical carcinoma.The presence of human papillomavirus (HPV) infection in the majority of cases of cervical neoplasia has been considered evidence of an etiological role of HPV in cervical cancer. The association is strong, consistent, and specific to a limited number of viral types (2,5,32,46). On the other hand, the lifelong risk of HPV infection is 80%, and only a small proportion of women infected with HPV will develop high-grade cervical neoplasia (42). Among HPV-positive women, it is therefore of the utmost importance to identify those with an increased risk of developing cervical carcinoma by either methods that reveal persistent HPV infection (38), methods that detect viral oncogene expression (40), or the use of additional human markers for cervical carcinogenesis (45).The most frequent HPV types found in cervical intraepithelial neoplasia and squamous cell carcinoma (SCC) are HPV type 16 (HPV-16) and HPV-18, which in 1995 were classified as human carcinogens by the International Agency for Research on Cancer. In total, based on their high frequencies in carcinomas, 13 HPV types are now considered carcinogenic types (6). In the largest multinational studies performed so far, HPV types 16, 18, 31, 33, and 45 were shown to be the most prevalent types associated with cervical carcinomas (2, 22, 32), with HPV-16 alone found in more than 50% of the cases. The oncogenic potential of these high-risk HPV types lies in the oncoproteins E6 and E7, which bind to and modulate a number of different gene products, in particular, the ...

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