East Asian Arch Psychiatry 2013;23:144-53

ORIGINAL ARTICLE

刘洁玲、严香华、张逸和

Dr Kit-Ling Lau, MBChB, FHKAM (Psychiatry), FHKCPsych, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.
Dr Patty Heung-Wah Yim, MBChB, MRCPsych, FHKCPsych, FHKAM (Psychiatry), Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.
Dr Eric Yat-Wo Cheung, MBBS, MRCPsych, FHKCPsych, FHKAM (Psychiatry), Castle Peak Hospital, Hong Kong, SAR, China.

Address for correspondence: Dr Kit-Ling Lau, Department of Psychiatry, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong SAR, China.
Tel: (852) 2595 6111; email: lkl368@ha.org.hk

Submitted: 7 May 2013; Accepted: 15 July 2013

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Introduction

Cervical cancer is the third most common cancer in women worldwide according to the latest cancer statistics.¹ In Hong Kong, cervical cancer is the seventh most common cancer among females. The median age at diagnosis is 53 years. It is the fourth most common cancer among young women aged 20 to 44 years.²

Cervical cancer is usually preceded by cervical intraepithelial neoplasia.³ With the earlier detection by cervical screening and more effective treatment, survival rates have significantly improved.¹ Despite improved survival rates, the treatment of cervical cancer often results in significant morbidity. The diagnosis of cervical cancer has physical, psychosexual, and psychosocial implications for the affected women.⁴ Cervical cancer survivors (CCS) frequently have to deal with bowel or bladder changes, sexual dysfunction, treatment-related menopause, loss of fertility, and relationship problems.⁵ Studies on CCS found that they had high rates of depressive and anxiety symptoms. It is important to identify psychiatric disorders in CCS, because depression and anxiety were shown to have a negative impact on their quality of life,^6,7 as well as potential deleterious effects on their immune system and medical outcomes.^8,9

Existing literature showed that CCS had a high prevalence of both depression and anxiety. However, all these studies relied on self-administered questionnaires to measure mood and anxiety symptoms rather than arriving at a definite psychiatric diagnosis based on structured psychiatric interviews. Moreover, apart from depression and anxiety, other psychiatric conditions, such as schizophrenia, have seldom been investigated.

This study therefore used the semi-structured diagnostic interview to determine the prevalence and nature of psychiatric disorders in CCS. Moreover, it looked for associated factors pertaining to any current psychiatric disorders, as such information might assist health care providers in identifying those at risk and facilitate appropriate interventions.

Methods

Study Design

This was a cross-sectional study conducted in a specialist outpatient clinic in the Department of Obstetrics and Gynaecology, Pamela Youde Nethersole Eastern Hospital. The majority of cervical cancer patients residing in Hong Kong Eastern District are referred to this clinic for staging, treatment, and follow-up. Hong Kong Eastern District serves a local population of approximately 0.8 million inhabitants. The data were collected over a year between May 2011 and April 2012. According to the protocol of the Department of Obstetrics and Gynaecology, after treatment all cervical cancer patients must be followed up at least annually; therefore the 1-year study period should have included all the existing CCS attending this clinic. Approval of the Ethics Committee was obtained before the study commenced.

Patients

All cervical cancer patients who had finished treatment were consecutively recruited when they attended the gynaecology clinic during the study period. Patients were excluded if they were not Chinese or younger than 18 years. Patients who were unable to communicate either verbally or by writing, or who had severe cognitive deficit such as mental retardation and dementia were also excluded. Written consent was obtained from all patients, and all of those diagnosed with psychiatric disorders were offered referrals to the psychiatric service.

Assessment

All psychiatric interviews were conducted using the locally validated Chinese-Bilingual Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Research version on each participant to establish DSM-IV diagnoses for both the current episode and any other lifetime occurrence. The participants completed the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which consists of 30 items (Appendix) and contains 5 functional scales (physical, role, emotional, cognitive, and social), a global quality-of-life scale, 3 symptom scales (fatigue, pain, and nausea / vomiting), and 6 single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties). The scoring of the EORTC QLQ-C30 was performed according to the scoring manual. A high score for a functional or global quality-of-life scale represents a relatively high / healthy level of functioning or global quality of life, and a high score for a symptom scale or item represents a more severe symptom or problem. Socio- demographic data, medical and psychiatric history, and clinical data were collected from the participants and their medical records.

Data Analyses

Data were analysed with the Statistical Package for the Social Sciences Windows version 16.0. All tests for statistical significance were set at 0.05. Descriptive statistics were used to characterise the socio-demographic and clinical profiles of the whole sample.

Frequency measures were obtained for psychiatric disorders. The diagnoses of major depressive disorder, dysthymic disorder, and adjustment disorder with depressed mood were categorised into depressive disorders group. The diagnoses of panic disorder, agoraphobia, social phobia, specific phobia, obsessive-compulsive disorder, post-traumatic stress disorder, generalised anxiety disorder, and adjustment disorder with anxiety were categorised into anxiety disorders group.

Categorical variables were analysed by the Chi- square test with Yates’ continuity correction; if more than 20% of the cells had expected counts of less than 5, Fisher’s exact test was used. For normally distributed continuous variables, independent sample t test was used for analysis, and the Mann-Whitney U test was used for non–normally distributed variables.

Variables associated with current psychiatric disorders with p < 0.1 in the univariate analysis were adopted as potential explanatory variables. Binary logistic regression with the stepwise forward method was employed to examine the impact of such variables on the development of current psychiatric disorders. Multicollinearity among variables was checked. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

Participants

Among the 117 patients being approached in the gynaecology clinic, 1 patient was excluded due to dementia, and 3 refused to participate. The main reasons of refusal were lack of time and dislike of being interviewed. The mean age of the non-participants was 72 years, which was higher than that of the remainder (60 years), but the difference did not reach statistical significance (p = 0.15). Overall, a total of 113 eligible patients were recruited, yielding a rate of 97%.

Socio-demographic Background

The mean age of the participants was 60 years. In all, 65 (58%) of the participants were married, 28 (25%) were widowed, 19 (17%) were separated or divorced, and 1 was single. Almost half (42%) of the divorce proceedings commenced after the cancer. The majority of participants (91%) had children. More than half (55%) of the participants had received a secondary or higher level of education. Besides, 32 (28%) of them were working, 77 (68%) were either homemakers or retired, and the remaining 4 were unemployed. Nearly half of them had a monthly household income of less than HK$10,000, and 19 (17%) were on social security assistance. Among the participants, only 4% were smokers and 5% were regular drinkers.

Medical and Psychiatric Background

In all, 90 (80%) participants had co-morbid physical illness, and 19 (17%) had a history of psychiatric illness. Among the latter, 9 had depression, 5 had anxiety, 3 had non- organic insomnia, and 2 had a psychosis. Moreover, 6 (5%) participants had a history of self-harm or suicidal attempts, 12 (11%) were actively receiving psychiatric treatment and being followed up in the public psychiatric service, whilst 10 (9%) reported a positive family history of psychiatric illness.

Cancer and Treatment Characteristics

In all, 97 (86%) participants had early-stage cervical cancer (stages 0 / I / II); 5 (4%) had a history of recurrence and all of them had completed treatment before being interviewed. The median elapsed interval since finishing treatment was 48 months. About half of them had cervical cancer diagnosed before the premenopause. In all, 57 (50%) participants received surgery only, 17 (15%) received radiotherapy only, 22 (20%) received both radiotherapy and chemotherapy, and the remaining 17 (15%) received a combination of surgery, radiotherapy and / or chemotherapy. The most common surgical treatment was hysterectomy with bilateral salpingo-oophorectomy, which was given to 47 (42%) of the participants. Four (4%) were currently receiving hormone replacement therapy. Urological symptoms were the most common side-effect (36%) experienced by the participants. Less commonly they had tingling or numbness (35%), sexual problems (21%), menopausal symptoms (20%), and lymphoedema (6%).

Health-related Quality of Life and Prevalence of Psychiatric Disorders

The participants’ EORTC QLQ-C30 scores are listed in Table 1. Findings pertaining to the point and lifetime prevalence of psychiatric disorders are summarised in Table 2. Among the 42 participants with current psychiatric disorders, 14 (33%) of them had 2 or more psychiatric diagnoses.

Factors Associated with Current Psychiatric Disorders

Compared with participants without current psychiatric disorder, those with current psychiatric disorders were found to be younger. They were also more highly educated, more likely to be receiving social security allowance, have a history of psychiatric illness and / or attempted self-harm or suicide (Table 3).

Cancer and Treatment Characteristics

Compared with those without current psychiatric disorders, a higher proportion of the participants with current psychiatric disorders had their cervical cancer diagnosed before the menopause, experienced urological symptoms, sexual problems, menopausal symptoms, and tingling or numbness (Table 4).

Health-related Quality of Life

Participants with current psychiatric disorders had significantly poorer performance in all domains of the EORTC QLQ-C30 than those without such disorders.

Factors Associated with Current Psychiatric Disorders in the Multivariate Analysis

Identified factors associated with current psychiatric disorders in the univariate analysis (i.e. p < 0.1) were age, education level, receipt of social security allowance, a history of psychiatric illness, a history of self-harm or suicidal attempt, premenopausal when diagnosed, menopausal symptoms, urological symptoms, sexual problems, tingling or numbness, and all domains of the EORTC QLQ-C30.

The EORTC QLQ-C30 functional scales and global health status were found to have multicollinearity problems with EORTC QLQ-C30 symptom scales / items, and were therefore not included in the multivariate analysis because they were not sufficiently specific.

There was multicollinearity between education level and age; premenopausal status at the age of diagnosis and age; a history of psychiatric illness and a history of self- harm or suicidal attempt; and receipt of social security allowance and financial difficulty. As a result, only age, a history of psychiatric illness, and receipt of social security allowance were selected.

Among the EORTC QLQ-C30 symptom scales / items, insomnia and loss of appetite were discarded because they were core symptoms of depression and therefore not independent of outcome. Although fatigue was also a symptom of depression, it was still included in the regression model because it was highly prevalent in cancer patients and acknowledged to be an important independent risk factor for depression in CCS.

After logistic regression, younger age (OR = 0.908, 95% CI = 0.855-0.964, p = 0.002), a history of psychiatric illness (OR = 24.789, 95% CI = 3.593-171.053, p = 0.001), menopausal symptoms (OR = 4.584, 95% CI = 1.131- 18.574, p = 0.03), pain (OR = 1.035, 95% CI = 1.008-1.063, p = 0.01), and fatigue (OR = 1.044, 95% CI = 1.015-1.074, p = 0.003) were found to be the independent predictors of current psychiatric disorder in CCS.

Discussion

Prevalence of Psychiatric Morbidity

In this study, the point prevalence of psychiatric disorders as a group in CCS was 37%. Depressive disorders and anxiety disorders were almost the only 2 groups of current Axis I psychiatric disorders identified. Acknowledging the limitation of comparing prevalence rates across studies with varying methodologies, the prevalence of current depressive disorders (31%) and anxiety disorders (16%) in our study were generally in line with estimated prevalences of 27 to 35% for depression and 18 to 40% for anxiety in CCS reported in previous literature using self-rated scales.^7,10-12 Thus, it appears that depression and anxiety are common in CCS across different cultures in different parts of the world.

In our study, the lifetime prevalence of any psychiatric disorder, major depressive disorder, and dysthymia were 43%, 24%, and 12%, respectively. A large local epidemiological survey known as the Shatin Community Mental Health Survey (SCMHS)¹³ reported corresponding figures of 18%, 2%, and 3% in the female general population. Clearly, local Chinese CCS had much higher rates of these disorders than the general population. A more recent local community survey¹⁴ reported a 12- month prevalence of major depression of 9.7% in females, which was nevertheless much lower than the 24% reported in the current study. The lifetime prevalence of generalised anxiety disorder in our study was 13%, which was much higher than the 6-month prevalence of 5% reported in a local community survey.¹⁵ Panic disorder was the second most common anxiety disorder and its lifetime prevalence of 7% was much higher than that in the SCMHS (0.34%).¹³

Our findings supported the notion that local Chinese CCS had higher prevalence of anxiety disorders than women in the general population.

One of our important findings was the high rate (33%) of co-morbidity between depressive and anxiety disorders. Patients with co-morbid depression and anxiety experience more severe symptoms, a longer time to recovery, use more health care resources, endure more functional impairment,^16,17 and have a higher suicidal risk.¹⁸ Thus, it is equally important to detect and treat depressive as well as anxiety disorders in CCS.

The high prevalence of depressive and anxiety disorders in CCS may have several reasons. In terms of psychosexual effects, the treatment of cervical cancer may permanently impair sexual function and reproductive viability, which can significantly impact a woman’s well-being.^19-21 A sizeable literature indicates that sexual dysfunction was more frequent in CCS than in the general female population.^19,21-24 Lack of lubrication and decrease in frequency of sexual activity were the most frequent complaints.⁴ A qualitative study conducted in mainland China entailed interviewing 35 CCS, and found that 37% of them reported complete cessation of sexual activity after their treatment or even since the diagnosis of cervical cancer.²⁵ Sexual inactivity was found to be a significant predictor of depression and anxiety in CCS in a large-scale Korean study.¹² In the present study, sexual problems were significantly associated with psychiatric morbidity in the univariate analysis, but the association became insignificant after other potential variables were controlled for in the logistic regression. Thus, it is possible that the effect size was not enough to be detectable with the sample size that prevailed in the present study.

From the psychosocial point of view, social rejection of cervical cancer patients is possible as this cancer has a direct link with sexual behaviour. Risky sexual behaviours, including sex at an early age, multiple sexual partners, and excessive indulgence in sex were perceived by Hong Kong Chinese women as a major cause of cervical cancer.²⁶ The labelling of promiscuity and unsafe sexual practices is often attached to the diagnosis of cervical cancer such that patients are often stigmatised and socially isolated.²⁵ Social support is known as one of the greatest and most powerful forces that facilitate successful adaptation when a person is challenged by cancer.²⁷ A local study investigating the quality of life of Chinese CCS found that in all age-groups they had lower scores on the social domain than healthy Hong Kong Chinese.²⁸ The literature also shows that low levels of social support were more frequently associated with depressive and anxiety symptoms in gynaecological and cervical cancer patients.^12,29 Nevertheless, such an association can be viewed in 2 ways. Cervical cancer may lead to social isolation, or the presence of depression may negatively influence patients’ perceptions of the level of social support.

From a biological perspective, the rapid cessation of oestrogen after cervical cancer treatment may be an additional risk factor. Oestrogen has profound effects on the central nervous system and can regulate various neurotransmitter receptors, including those of serotonin.³⁰ As a result, associations between oestrogen deficiency and psychological disturbance have long been investigated. Many researchers tried to investigate whether menopausal transition, in which there is a marked drop of oestrogen level, is a period of increased risk for depression.³¹ Despite extensive studies of this proposition, results with regard to such association remain inconclusive.³² However, such studies usually excluded the women who had undergone induced menopause. Induced menopause refers to the cessation of menstruation which follows either surgical removal of the ovaries with or without hysterectomy, or iatrogenic ablation of ovarian function (due to chemotherapy and radiotherapy).³³ Two population-based studies have demonstrated that women who had undergone induced menopause had significantly higher rates of depressive symptoms than those experiencing natural menopause.^34,35

Despite these findings, a causal relationship could not be established, as the necessary cross-sectional analyses were limited. Further prospective research should clarify the impact of induced menopause on the development of mood disorders.³²

Associated Factors for Psychiatric Disorders

Younger Age

Consistent with other literature on cancer survivorship, younger age was a significant predictor of psychiatric morbidity.^29,36-38 It has been suggested that younger patients had more difficulty accepting a diagnosis of cancer and experienced more mental health consequences from the diagnosis than older patients.³⁹ Moreover, in our culture younger age is generally associated with health, vitality, and fertility.²⁸ Concern over impaired fertility, femininity, treatment-related menopause, and relationship issues is likely to exert an adverse effect on the psychosocial adjustment to cervical cancer, particularly in women of childbearing age.^24,40

History of Psychiatric Illness

Unsurprisingly, patients with a psychiatric history appear more vulnerable to recurrences or perpetuation of their psychiatric illnesses when faced with a major stress. According to a review article, such relationships have been demonstrated in a number of studies on cancer patients.⁴¹

Fatigue

Fatigue was an independent factor significantly associated with current psychiatric disorders. Cancer-related fatigue is defined as ‘a persistent, subjective sense of tiredness related to cancer or cancer treatment, which interferes with usual functioning’.⁴² Its cause and mechanisms remain unclear, though it is known to differ from the fatigue experienced by the general population as it is not completely relieved by sleep and rest.⁴³ It is one of the most common complaints and is the most frequent and worst symptom reported by cancer patients.⁴⁴ It has a profound effect on the whole person and directly influences the desire to continue treatment.⁴⁴ Several studies have documented that fatigue was highly prevalent in CCS.^7,45,46 Cull et al⁷ found that 40 to 50% of women with early-stage cervical cancer treated by surgery or radiotherapy complained of chronic fatigue even 2 years after treatment. In a study by Vistad et al,⁴⁶ chronic fatigue was much more prevalent in CCS than in the general population (30 vs. 13%, p = 0.001), while in a multivariable analysis depression was the only variable significantly associated with chronic fatigue in CCS. Nevertheless, the bidirectional relationship between fatigue and psychiatric disorders should always be considered when interpreting this association.

Menopausal Symptoms

Presence of menopausal symptoms was another independent factor significantly associated with current psychiatric disorders in CCS. Menopausal symptoms (hot flushes and sweats)⁴⁷ were found to be more prevalent in CCS than in the general population even adjusted for age and menopausal status.^19,24 In a systematic review of community-based, prospective cohort studies of mid-life women transitioning through menopause,³² hot flushes were associated with an increased risk of depressive symptoms. A study by Frumovitz et al⁴⁸ reported that severity of menopausal symptom scores correlated with poor emotional quality of life among CCS who had undergone surgical menopause. In the current study, 23 (20%) women reported menopausal symptoms, but only 4 (4%) were in receipt of hormone replacement therapy. In terms of reducing distressing climacteric symptoms, it has been generally accepted that hormone replacement therapy was beneficial for CCS having an induced menopause.⁴⁹ Moreover, there was no evidence that hormone replacement therapy was related to the development or recurrence of cervical carcinoma.^49-51

Pain

In our study, pain was found to be significantly associated with current psychiatric disorders. A sizeable literature has confirmed that there is a strong relationship between pain and mood disturbance in cancer patients.^16,52 The relationship between pain and depression is complex. In depressed individuals, pathogenic pathways of both pain and depression involve serotonin and noradrenaline, low levels of which may affect pain modulation and exacerbate pain by amplifying minor signals and increasing attention to the symptom.⁵³ On the other hand, cancer pain is common and can be a chronic stress that adversely affects the psychological well-being of an individual.⁵² Despite being extensively studied, the causal relationship between pain and depression remains unresolved.⁵⁴ Compared with cancer- related fatigue, pain has been relatively less extensively investigated in CCS. Given its significant association with psychiatric disorders, more attention should be paid to its identification and treatment.

Clinical Implications

The frequency of psychiatric disorders, especially depressive and anxiety disorders, was high in Chinese CCS in our local / regional hospital. Those with current psychiatric disorders had significantly poorer performance in all domains of health-related quality of life than those without a current psychiatric disorder. However, less than one- fourth of these disorders were recognised and treated. The results of this study highlight the need for greater awareness and detection of psychiatric disorders among CCS.

The identification of associated factors related to current psychiatric disorders in CCS may contribute to the development of possible preventive measures. Younger age, a history of psychiatric illness, fatigue, pain, and menopausal symptoms were shown to predict current psychiatric disorder in CCS, about which gynaecologists have to be particularly aware of. During aftercare of CCS, gynaecologists should regularly screen for fatigue, pain, and menopausal symptoms, and be particularly alert to their mental condition. Optimising pain control is important and hormone replacement therapy should be considered for suitable patients.

Limitations

The cross-sectional design of this study did not allow for establishment of a causal relationship between associated factors and psychiatric disorders. Regarding the prevalence of psychiatric disorders, there was no control group to compare CCS with those without the cancer. The small sample size in this study might have jeopardised statistical power when investigating less common events or conducting sub-group analyses. Having a larger sample size, extending the duration of recruitment and / or conducting a multi- centre study, may facilitate more detailed analysis. In this study, certain variables (body image and perceived social support) shown to be important in relation to psychiatric disorders in CCS were not measured. However, employing recourse to yet more questions in the study may have reduced the response rate.

Conclusion

This study indicated that psychiatric disorders were prevalent among CCS in a regional hospital in Hong Kong, with depressive and anxiety disorders being the most common. Cervical cancer survivors with current psychiatric disorders had significantly poorer health-related quality of life in all domains compared with those without. The high prevalence and under-recognition of psychiatric disorders among CCS emphasise the need for improved identification of cases. Younger age, a history of psychiatric illness, fatigue, pain, and menopausal symptoms were found to be independent predictors of current psychiatric disorders in this patient group. Identification of these predictors can provide a useful framework to recognise at-risk patients and plan appropriate interventions. Future prospective research should examine the causal relationship between these factors and psychiatric disorders and evaluate the efficacy of psychosocial interventions.

Acknowledgements

I am most grateful to Dr Kwok-keung Tang, consultant of the Department of Obstetrics and Gynaecology, Pamela Youde Nethersole Eastern Hospital. It would have been impossible to perform this study without the collaboration of the entire clinical team.

Declaration

The author declared no source of financial support for the study.

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Appendix. Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.