Prevalence and Predictors of Anxiety and Depression Among Cervical Cancer Survivors in Korea

Kim, Soo Hyun RN, PhD*†; Kang, Sokbom MD, PhD‡; Kim, Yong-Man MD, PhD§; Kim, Byoung-Gie MD, PhD∥; Seong, Seok Ju MD, PhD¶; Cha, Soon Do MD, PhD**; Park, Chan-Yong MD, PhD††; Yun, Young Ho MD, PhD*

International Journal of Gynecological Cancer: August 2010 - Volume 20 - Issue 6 - pp 1017-1024
doi: 10.1111/IGC.0b013e3181e4a704
Cervical Cancer

Purpose: With increasing survival rates of women with cervical cancer, quality of life of the survivors becomes a more important issue. However, little is known about the mental health of cervical cancer survivors (CCSs). This study investigated the prevalence of anxiety and depression in CCSs compared with healthy controls and identified factors associated with multidimensional model including sociodemographic, clinical, functioning and well-being, and symptom variables.

Methods: The participants included 828 CCSs (mean time since treatment, 6.9 years) enrolled at 6 tertiary hospitals from 1983 to 2004 and 500 control subjects selected randomly from a representative sample of Korean women. Subjects completed the following questionnaires: the Hospital Anxiety and Depression Scale, the European Organization for Research and Treatment of Cancer Quality of Life questionnaire-C30, its Cervical Cancer module, and the McGill Quality of Life Questionnaire.

Results: Hospital Anxiety and Depression Scale-defined anxiety in CCSs did not differ from that in healthy controls (39.5% and 32.2%, respectively; P = 0.218). Anxiety was significantly more prevalent in younger CCSs (≤50 years) than in controls (40% vs 26.4%, respectively; P < 0.001). Hospital Anxiety and Depression Scale-defined depression was even lower in CCSs than in controls (34.6% vs 48.0%, respectively; P < 0.001). In multivariate analyses, the Hospital Anxiety and Depression Scale-defined anxiety and depression in CCSs were commonly associated with financial difficulty, poor body image, sexual inactivity, and low existential well-being. Low support and insomnia were uniquely related to anxiety, with older age and decrement role function uniquely related to depression. However, disease-related clinical factors were not related to either anxiety or depression.

Conclusions: Cervical cancer survivors showed relatively good mental health compared with healthy controls; however, women who have low functioning and well-being could be at high risk of anxiety or depression or both.

*Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi; †Department of Nursing, Inha University, Incheon; ‡Center for Uterine Cancer, National Cancer Center, Goyang, Gyeonggi; §Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine; ∥Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine; ¶Department of Obstetrics and Gynecology, Kangnam Cha Hospital, College of Medicine, CHA University, Seoul; **Department of Obstetrics and Gynecology, School of Medicine, Keimyung University, Daegu; and ††Department of Obstetrics and Gynecology, Gachon University, Gil Hospital, Incheon, Korea.

Received January 22, 2010, and in revised form March 25, 2010.

Accepted for publication April 24, 2010.

Address correspondence and reprint requests to Young Ho Yun, MD, PhD, Research Institute and Hospital, National Cancer Center, 809 Madu-dong, Ilsandong-gu, Goyang, Gyeonggi, Republic of Korea, 410-769. E-mail:

This work was supported by National Cancer Center grants 04101502 and 07104213.

There were no potential financial conflicts of interest.

Article Outline

Cervical cancer is the second most common cancer among women worldwide1 with persistently high incidence and mortality in developing countries. In Korea, the incidence has decreased significantly for the last 30 years, and the 5-year survival rate is relatively high (81.1%)2 with earlier detection and more effective treatments.

With the increasing survival rates of women with cervical cancer, the health-related quality of life (HRQOL) of the survivors has become a more important issue.3 The treatment of gynecological malignancies quite often results in significant morbidity and may involve multiple modalities (surgery, radiation, and chemotherapy). Women frequently must adjust to the physical, psychological, and sexual changes after treatment including loss of ovarian function, hot flashes, vaginal dryness, bowel or bladder changes, and mood changes.4

Previous QOL studies on the survivors of gynecological cancer have focused on physical symptoms and sexual problems.5-8 However, little is known regarding the mental health of cervical cancer survivors (CCSs).9 Moreover, few studies have compared mental health between CCSs and healthy controls. Anxiety and depression are major mental problems after cancer treatment. Many studies have reported these problems in approximately 20% of cancer survivors who completed their primary treatment,10-13 but this percentage varies according to the cancer site and study. The prevalence of depression and anxiety ranges from 9.7% to more than 33%9-12 and 19.2% to more than 38%, respectively.10-12 In the case of CCSs, only 2 studies have reported that the prevalence of depression was 27.6% and 33%,9,13 but there was no report of anxiety. In a recent critical review of HRQOL studies in gynecologic oncology, Vistad et al3 reported that anxiety and depression are rarely investigated using specific instruments.

The Hospital Anxiety and Depression Scale (HADS) is well accepted as a screening tool for anxiety and depression and has been recommended for use in oncology.14 The HADS has been used for long-term survivors of breast,11 testicular,10,12 and prostate cancers15,16 and in cancer patients undergoing therapy.17,18

This study attempted to expand our knowledge of the instance and levels of anxiety and depression in CCSs. The results from the CCSs were compared with the norm data from the Korean general female population. In addition, the factors associated with anxiety and depression among survivors were examined using a multidimensional framework including the sociodemographic, clinical, functional status and well-being, and symptom variables.

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Study Design

This study is a secondary analysis of the data collected in the quality of life study in CCSs19 conducted in Korea.

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Study Participants and Data Collection

Cervical Cancer Survivors

This study identified 7028 women who had been treated for cervical cancer at a gynecology oncology department in 1 of 6 hospitals in South Korea from 1983 to 2004. Information regarding the stage, histologic diagnosis, type of treatment, and other clinical characteristics was collected from the hospital cancer registries. The eligibility criteria included (1) a prior diagnosis of cervical cancer (stages I-IV), (2) prior treatment of cancer, (3) completion of primary cancer therapy, and (4) no history of other cancers. Potentially eligible women were contacted by telephone, and those who agreed to participate were sent a questionnaire with consent forms and a postage-paid return envelope. Subjects who did not return the questionnaire within 1 month received a reminder card and a telephone call.

Of the 7028 potentially eligible CCSs, 1085 (15.4%) had died. Multiple attempts were made to contact the others by postcard or telephone, but 3129 (44.5%) could not be contacted. The most common reason for contact failure was a change of address or telephone number. Of the 2814 women contacted, 32.9% refused to participate. Of the 1887 women who agreed to participate, 964 (51.1%) returned the questionnaire. The most common reasons the survivors gave for refusing to participate or not returning the questionnaire were that it was inconvenient (33.9%), they were too busy (18.6%), or they did not want to provide personal information (13.8%). Of the 964 women, those who did not receive any cancer therapy (n = 46) and those who were receiving their primary cancer therapy at the time of the survey (n = 90) were excluded. Therefore, the data from 828 survivors was analyzed. The overall response rate for the 5943 potential subjects was 13.9%.

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In 2005, surveys of the general population were conducted to assess the health behavior, psychological morbidity, and HRQOL as a reference database for cancer survivorship research. At each of the 15 provinces examined, the surveys were carried out in age and sex strata according to the guidelines of the 2000 Korean census. Details of the study design are reported elsewhere.20 The eligibility criteria included not having been a cancer patient and being able to complete a questionnaire or communicate with an interviewer. The interviewers visited each eligible person at home or at the workplace and explained the purpose of the study. This group completed the self-reported questionnaire in the presence of an interviewer, who explained the purpose of the study, but like the survivors, they completed the questionnaire for themselves without the interviewer's assistance. Only the data for women (n = 500) in the general population sample were used for all comparisons in this study.

All participants provided written informed consent, and the institutional review board of the Korean National Cancer Center approved the protocol.

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Anxiety and Depression

The HADS is a 14-item instrument that reflects 2 dimensions: 7 items on depression (HADS-D) and 7 items on anxiety (HADS-A).21 The HADS-D focuses mainly on the reduced pleasure response aspect (anhedonia) of depression, whereas the HADS-A focused mainly on the generalized anxiety issue of worry and fears about the future with 1 item for a panic attack.22 Each item is rated on a 4-point scale from 0 to 3, with a maximum of 21 each for anxiety and depression. High reliability has been demonstrated in previous studies (Cronbach α for HADS-A varied from 0.68 to 0.93 and for HADS-D from 0.67 to 0.90).22

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Functioning and Symptoms

Functioning and symptoms were measured with the subscales from the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire-C30 (QLQ-C30)23 and Cervical Cancer module (QLQ-CX24).24 The EORTC QLQ-C30 was scored according to the EORTC scoring manual,25 and the QLQ-CX24 was scored according to the developer's guideline. The QLQ-C30 and CX24 data were transformed linearly to yield scores from 0 to 100. A higher score represented a better level of functioning or a higher level of symptoms. Most of the functioning and symptom subscales from the EORTC QLQ-C30 and CX24 were used to predict the risk factors of anxiety and depression in CCSs. However, the emotional functioning results from the QLQ-C30 were excluded in the analyses because of conceptual overlap. Sexual/vaginal functioning and sexual enjoyment from QLQ-CX24 were excluded because of the large amount of missing data. The symptom experience scale was excluded because it was difficult to accept a subitem of symptom factors.

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Existential Well-Being and Support

Existential well-being and support were measured using the subscales from the McGill Quality of Life Questionnaire (MQOL).26 The MQOL is a multidimensional HRQOL questionnaire whose validity and reliability have been established in patients with chronic illness. The MQOL consists of physical, psychological, existential well-being, and support scales, of which the subscales within existential well-being and support were used. These subscales focus on the individual's ability to find meaning in their existence and achieve goals. They also cover issues of support. Each of these multi-item scales was scored from 0 to 10, with a higher score representing better well-being.

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Instrument Validation

The Korean versions of the HADS,27 EORTC QLQ-C30,28 QLQ-CX24,29 and MQOL30 have been validated.

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Data Management and Statistical Analyses

Descriptive statistics were used to present the overall characteristics of the study sample and examine the prevalence of anxiety and depression. This study examined the prevalence of clinically significant anxiety disorder, which is defined by a HADS-A score of 8 or greater, and the prevalence of clinically significant depression, which is defined by the same cutoff score on the HADS-D.11,22 This cutoff score was also validated in the study of the Korean population.27 These definitions of the disorders are supported by studies of sensitivity, specificity, and area under the curve in relation to the interview-based diagnoses in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition classification system of mental disorders.22 Based on the HADS cutoff scores, 4 additional categories of CCSs and controls were also defined: no disorder, HADS-A score lower than 8 and HADS-D score lower than 8; pure anxiety, HADS-A score of 8 or greater and HADS-D score lower than 8; pure depression, HADS-A score lower than 8 and HADS-D score of 8 or greater; and combined anxiety and depression, HADS-A score of 8 or greater and HADS-D score of 8 or greater.10 The means were compared using an independent t test and analysis of covariance, and the distribution of categorical variables was compared using the χ2 test. The odds ratio (OR) of being a survivor with a HADS-defined anxiety and depression disorder in CCSs for relevant variables was calculated using multivariate logistic regression models. Each independent factor found to be statistically significant (P < 0.05) at the univariate level was entered into the final multivariate logistic regression model. Using a backward stepwise elimination procedure, we obtained a best-fit multivariate logistic regression model. For continuous independent variables, we converted the dichotomous variables. Scores lower than 34 on the 0 to 100 scale for functioning scales in the EORTC QLQ-C30 and CX24 were considered to be indicative of a clinically significant functional problem31,32; scores of 66 or greater on the 0 to 100 scale for symptoms in these tests were considered indicative of clinically significant symptoms31,32; and a score lower than the 25th percentile was used as a cutoff score for the MQOL subscales. A P < 0.05 generated in a 2-sided test was considered statistically significant. The Statistical Package for Social Science (SPSS version 16.0; SPSS Inc, Chicago, Ill) was used to analyze the data.

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Sociodemographic and Clinical Characteristics

The mean (SD) age at the time of the survey was 50.4 (13.7) years, with a mean (SD) time since treatment of 6.9 (4.0) years. Table 1 lists the sociodemographic and clinical characteristics of the patients and the control women. The CCSs differed significantly from the control group in all sociodemographic characteristics. These sociodemographic variables were adjusted as covariates in the comparison of the prevalence of anxiety and depression between the 2 groups.

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Anxiety and Depression in CCSs and Controls

The 2 groups did not differ significantly in the mean level of anxiety (mean scores of CCSs and controls, 6.0 vs 5.9, respectively; P = 0.652). The prevalence of HADS-defined anxiety disorder was 39.5% in CCSs versus 32.2% in the controls (P = 0.218). A significant difference was found in the mean level of depression between the 2 groups (P < 0.001). However, the depression within the general population was higher than that in the CCSs (mean scores of CCSs and controls, 5.6 vs 7.6, respectively). Hospital Anxiety and Depression Scale-defined depression showed a prevalence of 34.6% in the CCSs versus 48.0% in the controls (P < 0.001; Table 2).

The proportion of survivors with pure anxiety was significantly higher among the CCSs, whereas the proportion of survivors with pure depression was significantly higher in the controls (Table 2). Figure 1 shows the prevalence of anxiety and depression among different age groups between the CCSs and the controls. Anxiety decreased with age in the CCSs, whereas depression generally increased with age. In the control women, both anxiety and depression generally increased with age. When the difference in both problems in the 2 groups was examined, younger CCSs (≤50 years) demonstrated significantly higher levels of anxiety than the controls, whereas older control women had significantly higher anxiety than the CCSs. All age groups among the controls except for those younger than 40 years showed a significantly higher prevalence of depression than the CCSs. However, the statistical significance for anxiety shown in the younger groups disappeared when controlling for other sociodemographic variables (eg, marital status, education levels, employment status, monthly income, religion, and comorbid condition; Fig. 1).

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Anxiety and Depression by Treatment Modality in CCSs

Women who underwent surgery and had adjuvant cancer therapy reported the highest anxiety and depression scores. However, there was no statistical significance according to the treatment modality (Table 3).

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Predictors of Anxiety and Depression in CCSs

To identify the factors associated with the development of anxiety and depression, univariate analyses of the associations between independent variables (eg, sociodemographic and clinical characteristics, functioning and well-being, and symptom variables) and anxiety and depression were carried out. Monthly income; physical, role, cognitive, and social functioning; fatigue; nausea/vomiting; dyspnea; insomnia; appetite loss; constipation; diarrhea; body image; lymphedema; peripheral neuropathy; menopausal symptoms; sexual worry; sexual activity; existential well-being; and support were significantly associated with anxiety. Age, education level, monthly income, and comorbidities were also significantly related to depression along with all functioning and symptom variables that were correlated with anxiety (data not shown).

In multivariate logistic regression analysis, a poor body image (ORs for anxiety and depression, 2.1 and 2.4, respectively), sexual inactivity (ORs, 2.0 and 2.3, respectively), financial difficulty (ORs, 1.8 and 2.3, respectively), and low existential well-being (ORs, 3.1 and 9.2, respectively) were commonly associated with anxiety and depression. Low support and insomnia were significantly associated with anxiety (ORs, 1.6 and 2.0, respectively), and age and poor role functioning were significantly related to depression (ORs, 1.9 and 2.8, respectively; Table 4).

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To our knowledge, this is the first large-scale investigation of the prevalence and associated factors for anxiety and depression among the CCSs (n = 828) who completed their primary treatment. Using a previously well-validated measure of anxiety and depression, the HADS, this study demonstrated that anxiety is more prevalent in CCSs than depression. Moreover, anxiety decreased with age, whereas depression generally increased with age. Compared with healthy controls, the proportion of CCSs with pure anxiety was significantly higher than the controls, and younger CCSs (≤ 50 y) had a higher rate of anxiety than the controls (40% vs 26.4%, respectively). In multivariate analysis, the 8 factors that explained anxiety and depression within the multidimensional model provided valuable information that highlighted the importance of functioning and well-being, including cervical cancer-specific issues (eg, body image and sexual activity) rather than disease- or treatment-related clinical factors.

The somewhat higher prevalence of anxiety and depression (39.2% vs 34.6%, respectively) in this sample than the results from Western countries (range, 19.2%-38% for anxiety and 9.7%-22% for depression)10-12 is not surprising because the prevalence in CCSs was comparable with that of healthy Korean controls and that of depression was even lower than the controls. Yun et al20 indicated higher levels of anxiety and depression in the Korean female general population, specifically for depression; Korean women showed similar prevalence of anxiety to Danish women (32.2% vs 31.1%, respectively) but reported 4 times the prevalence of depression (48.0% vs 11.4%, respectively). Hahn et al,33 using the Beck Depression Inventory to investigate the general population, found that the Beck Depression Inventory score for Koreans (≥13; cases = 49%) was higher than that for Westerners. The reason for the high prevalence of depression in Korean women may be because of Hwa-byung, a Korean term for an illness caused by suppressed anger.34 Koreans tend not to express their emotions but rather suppress their anger when faced with adversity.35 Because coping with anger in silence is related to depression in general36; the high prevalence of depression in Koreans may be a manifestation of Hwa-byung.

That younger CCSs (≤50 years) were more anxious than an age-matched control group was interesting. This finding is inconsistent with a study by Mehnert and Koch11 conducted among long-term survivors of breast cancer. Middle-aged women are strongly affected by their concerns regarding sexual function, provision of family needs, employment, or reestablishment of life roles in the family, workplace, and community.37 These issues may result in a higher prevalence of anxiety in middle-aged CCSs. However, caution should be taken when interpreting this result because the effect of age was not significant after controlling for other sociodemographic variables (P = 0.394) and was not a significant predictor in multivariate analyses.

Surprisingly, the prevalence of depression was lower in the patients than the healthy controls, which has also been reported by several other studies.11,12,16 We agree with the comments of Dahl et al10 in that acceptance by her partner, redefinition of values, and success in various life arenas can explain why cancer survivors are not more depressed than the general population in the long term. This long-term response shift could differ from patients with cancer immediately after diagnosis.

The importance of body image and sexuality issues among CCSs is well known. However, there is lack of evidence showing a specific association between these issues and mental health. Most studies demonstrated the problem itself5,7,38-40 or relationships with HRQOL,19 whereas the present study showed that women with problems of body image and sexual activity were almost twice as likely to report anxiety or depression than those without such problems. A longitudinal study of Figueiredo et al41 supports these findings. They found that body image is an important factor in making treatment decisions and that this predicted the 2-year mental health among older survivors of breast cancer. Health care professionals caring for CCSs need to be aware of their body image and sexual activity; they should make an effort to educate or counsel CCSs at a long-term follow-up and during the treatment phase.

The new finding that existential well-being is an independent predictor of both anxiety and depression (ORs, 3.1 and 9.2, respectively) is in line with the study reported by Shin et al.42 Cancer is a life-altering disease that often challenges one's view of the world, oneself, and one's future.42 Given the existential nature of these concerns, psycho-oncology clinicians have recently begun to recognize the importance of spiritual factors in the process of adapting to life after cancer.43 This finding supports previous studies indicating that the independent effects of existential well-being are strongly correlated with positive health outcomes in cancer survivorship.44 Kissane et al45 demonstrated that cognitive-existential group therapy is effective in reducing the level of anxiety in cancer patients. Enhancing the existential well-being might also play a key role in improving the mental health of cancer survivors.

Among other function-related factors, the role function was correlated with depression, as reported in previous studies.46,47 Cull et al13 reported that only 40% of the total sample of CCSs had resumed their full premorbid level of social activity within 2 years of the diagnosis, and 20% to 25% of them reported reduced performance in heavy housework, paid employment, leisure, and social activity. The issues of returning to work and leisure activities should also be considered to improve mental health in CCSs. In contrast to expectations, various symptom problems that were significantly associated with anxiety and depression in univariate analyses disappeared in the multivariate analyses. These results are not consistent with other reports in the literature.17,32,48-50 The present study found that only insomnia was a significant predictor of anxiety. It is possible that the impact of symptom problems was reflected in the functioning and well-being domain.

Among the sociodemographic factors, financial difficulty was identified as a significant predictor of both anxiety and depression, which is consistent with earlier studies.10,32 Recently, the Korean government began to give an insurance benefit to cancer patients and survivors; cancer patients receive 95% of the total medical cost from the government, and this benefit is to be expanded. Clinicians should also be aware of the health policy relating to the financial problems of cancer survivors.

There was no significant correlation between anxiety or depression and clinical factors (eg, treatment modality, time since treatment), which is in agreement with Bradley's study.9 Vistad et al3 reported that radiotherapy is more associated with a reduced QOL dimension including mental health than surgery or chemotherapy; women who had earlier stages of cervical cancer and surgery alone showed a better QOL. This discrepancy might be because our sample was composed of long-term survivors who were more affected by functioning or symptoms rather than treatment-related characteristics. There are few data on the impact of clinical factors on mental health in CCSs. Therefore, further research will be needed.

This study had several limitations. First, this study suffered from selection bias; although the study sample was population based, the response rate was only 14%. The amount of time that passed since the cancer diagnosis (1.4-22 years) and the reluctance to provide personal information, which is typical of Korean women, contributed to the low response rate. Compared with patients who responded to the questionnaire, nonresponders had their treatment a longer time ago (P < 0.01) and more had nonsurgery as their primary treatment (P < 0.01). The mental problems among CCSs may have been underestimated because nonresponders may have had higher levels of anxiety and depression. Second, the causal effects between independent variables and anxiety and depression could not be identified because of the cross-sectional study design.

Despite these limitations, it is believed that this study has improved the understanding of anxiety and depression in CCSs. In addition, a well-established instrument (HADS) with good psychometric properties for a large-scale assessment of mental health was used, and the results could be compared with the norm data of women from the Korean population. These findings of the prevalence and associated factors for anxiety and depression will be helpful for developing clinical management strategies to improve the mental health of this population. It is believed that an education program of body image and/or sexuality, individual counseling (ie, sexuality and financial problems), or cognitive-existential group therapy could be effective in improving the mental health of CCSs.

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Anxiety; Depression; Cervical cancer; Survivors

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