Cervical cancer is the second most common and the fifth deadliest malignancy among women worldwide (1–3). Patients with recurrent cervical cancer exhibit a very high mortality, despite several currently available treatment options, although central-local recurrences, most likely due to a better clinical response to chemoradiation therapy, have a better overall survival rate compared to lateral-pelvic recurrences (45.4 vs. 18.2%, respectively) (4–6). Previous studies have demonstrated that lymph node metastasis, parametrial and surgical margin involvement, tumor size and deep stromal invasion, but not histological type or grade, significantly affect cervical cancer recurrence (7–10). However, the risk factors that are considered to contribute to cervical cancer recurrence are not universally accepted or duplicated in other study populations. Furthermore, the risk factors contributing to early recurrence (<2 years) have not been investigated, although recurrence and metastasis of cervical cancer contribute to a poor prognosis. Other molecular analyses have demonstrated that altered expression of different genes predicts early recurrence of cervical cancer (7–10), but these may not be superior to routine clinicopathological parameters (7–10). Thus, in this study, we aimed to perform a retrospective analysis of 284 cervical cancer patients with disease recurrence in order to determine the association of their clinicopathological parameters with early cervical cancer recurrence.

Cervical cancer remains a significant public health concern worldwide (2, 5, 6), particularly among women aged ≤65 years or in developing countries (11–13). Approximately one-third of patients with invasive, recurrent, or metastatic cervical cancer eventually succumb to the disease. The recurrence rate of cervical cancer ranges from ∼ 10% for International Federation of Gynecology and Obstetrics stages Ib-IIa to ∼ 60% in locally advanced cases (stages IIb-IVa) (14). The mortality rate in patients with early recurrence is even higher (14). Previous studies identified several risk factors, such as tumor size and lymph node metastasis, which are associated with the recurrence of cervical cancer (7–10). Consistently, in our present study, we identified tumor size as an independent risk factor associated with early recurrence of cervical cancer. Furthermore, our data identified patient age and tumor appearance as independent risk factors contributing to early recurrence of cervical cancer.

Over the last few years, the incidence of cervical cancer has increased among younger women; furthermore, younger patients with cervical cancer have a worse clinical outcome (15, 16). Our present findings demonstrated that patient age was an independent determining factor for early recurrence of cervical cancer, which was consistent with the findings of previous studies (15, 16). Compared to older patients, younger cervical cancer patients often exhibit the following characteristics : immune deficiency; tobacco smoking; high serum hormone levels; cervical erosions; HPV16 infection; and high levels of survivin, cyclooxygenase 2, matrix metalloproteinase and CD44 expression. In addition, younger patients with cervical cancer also exhibit poor tumor differentiation and lymph node metastasis. These characteristics may collectively contribute to early recurrence of cervical cancer in this patient population. Thus, the age of the patient requires careful consideration in the treatment of cervical cancer.

Previous studies demonstrated that a cervical cancer lesion with a diameter >4 cm is more difficult to control compared to smaller lesions (17, 18). The reason may be that large tumor lesions are more frequently associated with an earlier onset of distant tumor metastasis (17, 18). Large cervical cancer lesions with a cauliflower-like and ulcerative tumor appearance often lack sufficient blood supply in their lesion center; thus, they subsequently recruit hypoxic cells and are more resistant to radiation therapy. Furthermore, exophytic cervical cancers often destroy the normal appearance of the cervix, which is likely to affect the pelvic radiation dose distribution and reduce the effective radiation dose administered to the tumor cells. All these factors may result in difficult control of these large, exophytic, ulcerated cervix cancers, subsequently causing early recurrence or metastasis. Therefore, in accordance with the 2012 National Comprehensive Cancer Network Cervical Cancer Clinical Practice Guidelines, such patients should be treated by radical surgery with chemoradiotherapy. Chemotherapy enhances the radiosensitivity of tumor cells for better local control and also controls potential distant tumor metastasis. If the patients fail to show local control following radiotherapy, surgical removal of local tumor lesions should be considered, which may help control tumor progression, reduce recurrence and improve patient outcome (19–21). These reasons may explain why patient age, tumor appearance and tumor size are independent factors for cervical cancer recurrence and they should be considered for future management of cervical cancer. However, several factors, such as patient age and tumor size, stage and localization, may also affect the outcome or therapeutic decisions made in cervical cancer patients. In this patient cohort, only patient age and tumor appearance and size were identified as independent predictors of recurrence and metastasis of cervical cancer, whereas treatment selection (radiation vs. surgery) and clinicopathological stage did not predict recurrence or metastasis of cervical cancer. Thus, future studies are required to verify our findings prior to their application in clinical practice.