ABSTRACT
HPV genotyping is an important tool in the epidemiology and surveillance of HPV-associated cancers and for the risk-stratification of HPV infections. HPV sign Genotyping Test (QIAGEN) is a new pyrosequencing assay for the detection and genotyping of HPV. The sensitivity and comparative performance of HPV sign was determined using a sample panel derived from histologically confirmed cervical lesions (cervical intraepithelial neoplasia 2 or worse) and oropharyngeal squamous cell carcinomas. Comparative analysis showed that 80% of cervical intraepithelial neoplasia 2+ and 81% of oropharyngeal squamous cell carcinomas were HPV-positive by HPV sign compared to 100% of the cervical intraepithelial neoplasia 2+ and 81% of oropharyngeal squamous cell carcinomas by the digene HPV Genotyping RH Test (RH), and INNO-LiPA HPV Genotyping Extra assay, respectively. Fewer genotypes were detected overall by HPV sign than via the relevant comparator assays (10 vs 21 for cervical intraepithelial neoplasia 2+; 4 vs 9 for oropharyngeal squamous cell carcinomas) and also fewer multiple infections (9 vs 28 for cervical intraepithelial neoplasia 2+; 0 vs 4 for oropharyngeal squamous cell carcinomas). HPV sign results were more compatible with the comparator assay for the oropharyngeal squamous cell carcinoma samples (100%) than for the cervical samples (73%). These results suggest that HPV sign in its current form is suited to samples that harbour multiple infection.
Subject(s)
Carcinoma, Squamous Cell/virology , Genotyping Techniques/methods , Molecular Diagnostic Techniques/methods , Oropharyngeal Neoplasms/virology , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Uterine Cervical Neoplasms/virology , Female , Humans , Papillomaviridae/classification , Papillomaviridae/genetics , Papillomavirus Infections/virology , Sensitivity and Specificity , Virology/methodsABSTRACT
The SRC family of ER co-regulators are frequently overexpressed in breast cancer. Overexpression of AIB1 appears to be linked to hormone resistance in HER2 positive breast cancer. However, the role of these co-regulators in ER negative disease is poorly understood. SRC1, SRC2 and AIB1 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate tumours that overexpress both HER2 and AIB1 were associated with markedly reduced relapse free, distant relapse free and overall survival compared to HER2 and AIB1 only overexpressing tumours irrespective of ER status. In ER negative disease both SRC1 and AIB1 were linked to early relapse and death. The SRC family of ER co-regulators is involved in early relapse and resistance in both ER negative and ER positive breast cancer challenging the conventional concept that this effect is mediated solely via the ER.
