[Hypoxia in cervical cancer: pathogenesis, characterization, and biological/clinical consequences]

Approximately 60% of locally advanced carcinomas of the uterine cervix exhibit hypoxic and/or anoxic tissue areas which are heterogeneously distributed within the tumor mass. Hypoxia is caused by structural and functional abnormalities of the newly formed tumor vessels arising from neovascularization, by a disturbed microcirculation, enlarged diffusion distances and by tumor- or therapy-associated anemia. The extent of pretherapeutically measured hypoxic tissue areas is independent of clinical size, FIGO stage and histopathological grade of squamous cell carcinomas of the uterine cervix. Anemia can intensify tumor hypoxia. O2-tensions in local recurrences are even lower than those in the primary tumors. About 78% of recurrent tumors exhibit hypoxic tissue areas. Hypoxia is known to directly or indirectly (e.g., via cell cycle effects) affect the therapeutic efficacy of sparsely ionizing radiation and some forms of chemotherapy. Sustained tissue hypoxia may also cause molecular changes that can result in a more malignant phenotype, a process termed malignant progression. Based on this association between tumor hypoxia and malignant progression, tumor oxygenation has proven to be an independent, powerful prognostic factor of local control, overall and disease-free survival. In addition, the routine evaluation of the pretherapeutic oxygenation status may enable individual therapeutic strategies, independent of other oncologic parameters.