The annual global incidence of cervical cancer is approximately 604 000 cases/342 000 deaths, making it the fourth most common cancer in women. Cervical cancer is a major healthcare problem in low and middle income countries where 85% of new cases and deaths occur. Secondary prevention measures have reduced incidence and mortality in developed countries over the past 30 years, but cervical cancer remains a major cause of cancer deaths in women. For women who present with Fédération Internationale de Gynécologie et d’Obstétrique (FIGO 2018) stages IB3 or upwards, chemoradiation is the established treatment. Despite high rates of local control, overall survival is less than 50%, largely due to distant relapse. Reducing the health burden of cervical cancer requires greater individualization of treatment, identifying those at risk of relapse and progression for modified or intensified treatment. Hypoxia is a well known feature of solid tumors and an established therapeutic target. Low tumorous oxygenation increases the risk of local invasion, metastasis and treatment failure. While meta-analyses show benefit, many individual trials targeting hypoxia failed in part due to not selecting patients most likely to benefit. This review summarizes the available hypoxia-targeted strategies and identifies further research and new treatment paradigms needed to improve patient outcomes. The applications and limitations of hypoxia biomarkers for treatment selection and response monitoring are discussed. Finally, areas of greatest unmet clinical need are identified to measure and target hypoxia and therefore improve cervical cancer outcomes.
- cervix uteri
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Contributors All contributors have critically reviewed the papers included in the review and have helped write the submission. In particular, CW provided expertise on hypoxia radiobiology and tissue derived biomarkers. JPBO provided expertise on imaging biomarkers. AC and PH provided expertise on the clinical problem of cervical cancer and the role of hypoxia targeting agents.
Funding AD is on a 3-year Cancer Research UK funded PhD (Award ID: A28707). This work is also supported by the NIHR Manchester Biomedical Research Centre.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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