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Gynecologic Cancer Editorial Why We Need to Continue to Research Ways to Improve the Treatment of Locally Advanced Cervical Cancer Linda Mileshkin, MD Medical Oncologist, Division of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia Abstract Morbidity and mortality from locally advanced cervical cancer continues to be a major problem worldwide. Clinical research has defined the best approaches to standard therapy currently. However, it is essential that international clinical trials in this disease continue to be supported to improve outcomes globally. Keywords Cervical cancer, chemoradiotherapy, HPV Disclosure: Linda Mileshkin, MD, has nothing to declare in relation to this article. No funding was received in the publication of this article. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: September 20, 2015 Published Online: November 10, 2015 Citation: Oncology & Hematology Review, 2015;11(2):110–12 Correspondence: Linda Mileshkin, MD, Medical Oncologist, Division of Cancer Medicine, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett St, Vic 8006, Australia. E: firstname.lastname@example.org Cervical cancer remains one of the leading causes of cancer-related morbidity and mortality worldwide, and is the fourth leading cause of cancer death in women. 1 Human papilloma virus (HPV), particularly types 16 and 18, is significantly associated with subsequent development of cervical cancer, with an increased risk also seen among smokers. 2 Cervical cancer incidence has decreased in developed countries since the widespread introduction of cervical screening. 3 However, it remains a major health problem in countries without screening programs and in disadvantaged communities within developed countries with screening programs. 2,4,5 For example, indigenous Aboriginal and Torres Strait Islander women have double the incidence and five times the mortality risk than other Australians. 6–9 Many patients with cervical neoplasia have early lesions detected by Pap smear, which are curable with surgery. However, screening rates are low in women from disadvantaged areas, even in developed countries. Hence we continue to see women present with locally advanced diseases who have much lower cure rates. 10–12 In addition, there difficulties continue with detecting the precursors of adenocarcinomas using Pap smears. The development of the cervical cancer vaccine is a major advance, which will reduce cervical cancer rates for future generations. Realizing the benefit of the vaccine is predicted to take some time given that the incidence of cervical cancer continues to rise with age, and that ongoing screening will be required in addition to the vaccine program, which needs to be initiated prior to the age of commencement of sexual activity to be 110 effective. The current vaccine that has been in clinical use is predicted to protect against 70 % of cervical cancer, but does not provide protection for the 30 % of chronic infections by HPV types other than HPV 6, 11, 16, and 18 and has no role in the treatment of established cancer. 1 However, in December 2014, the US Food and Drug Administration (FDA) approved a nonavalent vaccine, which offers protection against seven high-risk HPV subtypes and appears even more effective. A UK modeling analysis suggests that 60 years of an ongoing vaccination program of 12-year- old girls at 80 % coverage will be required to see a 38–82 % reduction in cervical cancer incidence if vaccine protection lasts for 20 years on average. 13 Unfortunately, many countries worldwide still have neither screening nor vaccination programs so the need to treat locally advanced cervical cancer will remain a problem in our community for many years and needs ongoing research. The use of low-dose chemotherapy concurrent with pelvic radiation has been proven to improve survival for locally advanced cervical cancer. 14 The Medical Research Council (MRC) individual patient data meta-analysis found that the addition of concurrent chemotherapy to radiation increased the 5-year overall survival rate by 6 % (HR 0.81: 60 versus 66 %). 15 On the basis of the studies in this analysis, weekly cisplatin at a dose of 40 mg/m 2 during pelvic radiation has become the standard of care for the treatment of locally advanced disease. However, the 5-year disease-free survival rate was only 58 % in the chemoradiation group, which, although superior to 50 % with radiation alone, still leaves significant room for improvement. Although chemoradiation is a generally effective treatment for the Touch ME d ica l ME d ia