Northern Institute of Cancer Research, University of Newcastle upon Tyne, Paul O'Gorman Building, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
* Email: p.k.wright{at}ncl.ac.uk
Human papilloma virus (HPV) testing and sentinel node biopsy both represent significant advances in the diagnosis and management of cervical cancer. In the June 2004 issue of Annals of Oncology, two papers draw attention to these techniques. Dannecker et al. [1] showed that self-testing may be a facile means of sampling in cervical cancer screening, and Barrenger et al. [2
] illustrated the potential of sentinel node biopsy applied to cervical cancer. Although both of these papers contribute significantly to the current knowledge and opinion regarding the diagnostic options available for cervical cancer, I believe that both techniques will eventually be largely circumvented by DNA microarrays.
Cytology is essentially a 19th century technology. Despite refinements including the Pap stain, its overall potential has not changed vastly since the resolving power of the light microscope reached the physical limit. Cervical cytological screening has reduced the incidence and mortality of cervical cancer. However, it has a relatively low sensitivity and reproducibility [3]. The interpretation of cervical cytology is a subjective visual recognition skill rather than a specific laboratory test. It is limited by cellular sampling, human error and, most of all, by its reliance purely on the appearance of the cellular phenotype to predict diagnosis.
HPV testing may be a useful adjunct to cervical cytological screening as it has the potential to be used as an objective diagnostic assay. However, despite this, the majority of cervical HPV infections resulting in dyplasia resolve. Therefore, HPV testing cannot provide the sole solution to cervical cancer screening and diagnosis.
DNA microarrays have been shown to be capable of diagnosing a variety of cancers and to provide diagnostic and prognostic information that is unavailable from cytopathology or histopathology [4]. Beyond diagnosis of cancer, DNA microarrays have been shown to have the ability to predict metastasis. In particular, DNA microarrays have been shown to predict lymph node metastasis, for example in breast cancer [5
]. Therefore, patients could have the benefit of accurate diagnosis as well as the avoidance of minimally invasive but not risk-free sentinel node biopsy. With the advent of global human genome DNA microarrays such as the Affymetrix® Hu U133 Plus 2.0 GeneChip®, it is likely that even greater diagnostic accuracy will be attained.
Limitations of DNA microarrays include the cost and the labile nature of RNA, which is subject to degradation, as well as transcriptome variations secondary to artefacts including hypoxia-induced gene induction. The answer to these limitations may be either to use defined protocols with agents such as RNAlater® combined with a cheaper, focused DNA microarray with probes for several hundred key genes. Alternatively, the solution may be to develop a protein-based diagnostic assay using a panel of protein markers developed from DNA microarray research, perhaps ultimately in the form of a protein microarray. Biomarkers have already been identified in cervical cancer using DNA microarrays [6]. I look forward to the results of further DNA microarray studies on cervical cancer in the current era of high-throughput technologies.
![]() |
References |
---|
![]() ![]() |
---|
2. Barranger E, Cortez A, Commo F et al. Histopathological validation of the sentinel node concept in cervical cancer. Ann Oncol 2004; 15: 870874.
3. Fahey MT, Irwig L, Macaskill P. Meta-analysis of Pap test accuracy. Am J Epidemiol 1995; 141: 680689.[Abstract]
4. Fey MF. Impact of the Human Genome Project on the clinical management of sporadic cancers. Lancet Oncol 2002; 3: 349356.[CrossRef][ISI][Medline]
5. Huang E, Cheng SH, Dressman H et al. Gene expression predictors of breast cancer outcomes. Lancet 2003; 361: 15901596.[CrossRef][ISI][Medline]
6. Chen Y, Miller C, Mosher R et al. Identification of cervical cancer markers by cDNA and tissue microarrays. Cancer Res 2003; 63: 19271935.
|