For patients with cervical cancer treated with definitive CCRT or radiotherapy, the level of SCC Ag normalized in most patients who had a complete response [
27]. However, 20–30% of patients suffered from tumor relapse during follow-up [
2,
7,
16,
22,
28]. Early detection of tumor relapse has a significant impact on prognosis and may improve the survival of patients [
29]. Among cervical cancer patients with tumor relapse, 62.3–82.4% had elevated SCC Ag levels before the diagnosis of tumor relapse [
28,
30,
31].
In the surveillance of cervical cancer, the Society of Gynecologic Oncology (SGO) [
32] and National Comprehensive Cancer Network guidelines [
4] recommend a medical history, a physical examination, cervical/vaginal cytology and imaging as indicated based on symptoms or suspicion for recurrence. However, assessment of SCC Ag is not currently recommended. Oh et al. analyzed 53 patients with locally advanced cervical cancer who were primarily treated with definitive CCRT or radiotherapy and experienced tumor relapse and found that adding SCC Ag assessment to the basic follow-up protocol recommended by the SGO may improve sensitivity for detecting tumor relapse. The sensitivity of the basic protocol and the basic protocol plus the SCC Ag protocol were 49.1 and 88.7%, respectively (p < 0.001). Early diagnosis of tumor relapse that can be treated by salvage therapy, which may lead to better survival [
30]. Another study by Oh et al. demonstrated that the optimal cutoff value of the SCC Ag level for detecting tumor relapse was 2 ng/ml [
33]. Yoon et al. reviewed the records of 116 patients with cervical cancer who were treated with CCRT and found that 18 developed recurrent disease. The change in SCC Ag (ΔSCC Ag), which is defined as the difference between the last elevated value and the value immediately before elevation, might accurately predict tumor relapse. The optimal cutoff value of ΔSCC Ag was 0.95 ng/ml. The true positive and false positive rates were 75 and 11%, respectively [
34]. In a study by Forni et al., the sensitivity, positive predictive value and negative predictive value of SCC Ag were 79.1, 89.5 and 90.7%, respectively, during the follow-up of patients with cervical cancer treated with radiotherapy or CCRT; the cutoff value was 1.4 ng/ml. In a study by Hu et al., the sensitivity and positive predictive value of SCC Ag in detecting tumor recurrence of cervical cancer were 72.1 and 96.9%, respectively [
35]. Compared with the complete follow-up protocol, the recurrence miss rate of the simplified approach (SCC Ag plus gynecologic examination) was 2.2%. The cost-effectiveness profile of the simplified approach was better than that of the standard approach [
31].