Fertility anxiety partially mediates depression and recurrence fear in reproductive-age cervical cancer patients: A cross-sectional study

Abstract

BACKGROUND

Cervical cancer survivors of childbearing age often face heightened reproductive anxiety due to the direct impact of the disease and its treatments on fertility. This anxiety may exacerbate psychological burdens, including depressive symptoms and fear of recurrence, significantly impacting quality of life.

AIM

To examine whether reproductive concerns partially mediate the relationship between depressive symptoms and fear of recurrence in cervical cancer patients of childbearing age.

METHODS

Utilizing a cross-sectional design with convenience sampling, 208 eligible cervical cancer patients (aged 18-45 years, stable condition, and aware of diagnosis) from three tertiary hospitals completed validated questionnaires: The Reproductive Concerns After Cancer Scale, Patient Health Questionnaire-9, and Fear of Cancer Recurrence Questionnaire. Structural equation modeling was used to assess the mediating role of reproductive concerns in the relationship between depression and fear of recurrence.

RESULTS

Reproductive concerns demonstrated significant positive correlations with depression (r = 0.477, P < 0.001) and fear of recurrence (r = 0.426, P < 0.001). Structural equation modeling analysis revealed that reproductive concerns acted as a significant partial mediator between depression and fear of recurrence. The indirect effect via reproductive concerns was significant (β_indirect = 0.152, P < 0.001), accounting for 28.1% of the total effect of depression on fear of recurrence.

CONCLUSION

Identified path reveals fertility anxiety links depression to recurrence fear. Targeted psych interventions for repro concerns may ease both in childbearing cervical cancer survivors.

Key Words: Uterine cervical neoplasms; Depression; Fear; Fertility preservation; Mediation analysis; Reproductive age

Core Tip: This study establishes reproductive concerns as a significant partial mediator (accounting for 28.1% of the total effect, β-indirect = 0.152, P < 0.001) between depression and fear of recurrence in 208 childbearing-age cervical cancer patients, using validated scales (Patient Health Questionnaire-9, Reproductive Concerns After Cancer Scale, Fear of Cancer Recurrence Questionnaire) in a cross-sectional design. Strong correlations were observed (reproductive concerns with depression: r = 0.477; with fear of recurrence: r = 0.426), highlighting that depression amplifies fear of recurrence both directly (β-direct = 0.389) and indirectly via fertility-related distress. Given cervical cancer's direct impact on reproductive function and cultural childbearing expectations in populations like China, targeted oncofertility counseling and psychosocial interventions addressing reproductive concerns may concurrently alleviate depressive symptoms and recurrence fears, offering a dual-benefit strategy for survivorship care.

INTRODUCTION

Cervical cancer remains a critical global health burden, with recent GLOBOCAN data reporting 604000 new cases and 342000 deaths annually worldwide[1]. A significant clinical concern is the rising incidence among younger women, with approximately 43% of patients diagnosed before age 45 years[2]. This demographic group faces unique challenges: Treatments (e.g., radical hysterectomy and radiotherapy) frequently cause irreversible reproductive damage[2], while cultural expectations in China emphasize childbearing responsibilities[3]. Consequently, fertility preservation becomes paramount, especially for childless patients[4].

The convergence of disease impact and fertility threat drives substantial psychological distress. Reproductive concerns-a multidimensional construct encompassing fertility potential, pregnancy feasibility, and offspring health anxieties-are central to this distress. The Reproductive Concerns After Cancer Scale (RCAC), developed by Gorman et al[5] and validated in Chinese populations[6], quantifies these issues. Concurrently, depression and fear of recurrence represent prevalent psychological sequelae in gynecological oncology[7,8]. Substantial evidence confirms their association; notably, breast cancer studies demonstrate significant correlations between Patient Health Questionnaire-9 (PHQ-9) depression scores and fear of recurrence severity[9], with similar patterns observed in Chinese cervical cancer cohorts[10].

We propose that reproductive concerns may mediate the depression–fear of recurrence relationship: Depressive symptoms, characterized by negative cognitive schemas[11], likely amplify fertility-related distress. This heightened reproductive concern may exacerbate broader fears about disease trajectory and recurrence[12], particularly concerns about insufficient survival time to raise children or parenting abilities compromised by recurrence. While studies document associations among these variables in breast cancer[9,12], formal mediation analysis is absent for cervical cancer populations, despite their heightened reproductive vulnerability[2].

Therefore, this study aimed to test whether reproductive concerns partially mediate the association between depressive symptoms and fear of recurrence in cervical cancer patients aged 18-45 years.

MATERIALS AND METHODS

General information

This cross-sectional survey study utilized a convenience sampling method to recruit eligible cervical cancer patients from three tertiary-level A hospitals in China: Nanjing Women and Children's Healthcare Hospital, Nanjing Gulou Hospital, and the Cardiovascular and Cerebrovascular Disease Hospital of the General Hospital of Ningxia Medical University. Data collection occurred between September 2022 and October 2023. Of the 210 patients recruited, two were excluded due to incomplete questionnaires, yielding 208 valid responses (99.05% effective rate) for final analysis. Inclusion criteria: (1) Aged 18-45 years; (2) Diagnosed with cervical cancer per the Guidelines for the Diagnosis and Treatment of Cervical Cancer (2021 Edition)[13], confirmed via pathology/imaging; (3) Aware of diagnosis and clinically stable; (4) Fully conscious, communicative, and cooperative; and (5) Written informed consent. Exclusion criteria: (1) Infertility; (2) Expected survival < 1 year; (3) Distant metastasis or other malignancies; (4) Severe comorbidities (e.g., cardiopulmonary/cerebrovascular diseases); (5) Use of psychotropic drugs within 3 months prior to the survey; and (6) Voluntary withdrawal during the study. Based on the guideline requiring 10-20 times the number of independent variables[14] and anticipating 13 variables, 210 participants were initially recruited (accounting for a 15% potential exclusion rate). This study was reviewed and approved by the Ethics Committee of Nanjing Maternal and Child Health Hospital (No. 2022KY-135-2) and registered at ChiCTR (ChiCTR2300076052). Written informed consent was obtained from all participants.

Survey instruments

General information questionnaire: The questionnaire was designed for this study, and after obtaining the consent of the hospital and department, data related to the clinical information of the patients were collected from the electronic medical records using a two-person checking system. Data mainly included patients' age, ethnicity, place of residence, marital status, number of children, education level, per capita family income, occupation, medical payment method, and tumor type and stage.

Reproductive concerns

Of Young Adult Female Cancer Scale (RCAC): The scale was compiled by Gorman et al[15], translated and sinicized by Qiao et al[6], and contained six dimensions: Ability to conceive (3 entries); preparation for pregnancy (3 entries); spousal knowledge (3 entries); own health (3 entries); children's health (3 entries); and disease acceptance (3 entries), totaling 18 entries. Each entry was scored on a 5-point scale of 1-5, with a total score of 18-90, with higher scores indicating greater fertility anxiety. The scale was validated for reliability and validity, with an overall Cronbach's α coefficient of 0.831.

Depression screening scale (PHQ-9): The scale was developed by Gui et al[16], translated and sinicized by Farag et al[17], and contains nine entries. Each entry was scored on a 4-point scale of 0-3, and patients were asked to self-rate the frequency of symptoms experienced in their lives over the past 2 weeks, with a total score of 0-27, with ≥ 5 indicating the presence of depressive symptoms, and higher scores indicating more severe depressive symptoms. The scale was validated for reliability and validity, with an overall Cronbach's α coefficient of 0.896.

Fear of Cancer Recurrence Questionnaire: The scale was compiled by Humphris et al[18] in the United Kingdom, translated and sinicized by Zhang et al[19], with a total of seven entries. The first six were scored on a 5-point scale from 1 to 5, and the seventh entry was scored on a 10-point scale from 1 to 10, with a total score of 7-40, with higher scores indicating a greater degree of fear of recurrence. The scale was validated for reliability and validity, with an overall Cronbach's α coefficient of 0.892.

Data collection and quality control

All questionnaire data were collected online. Investigators underwent a 1-week standardized training. After obtaining consent, patients received unified instructions. Surveys were anonymous and self-administered. If patients were unable to complete the survey independently, trained nurses assisted by reading questions aloud and recording responses. Clinical data (tumor type and stage) were abstracted from electronic medical records by two independent researchers using dual verification. Pilot testing with 10 eligible patients informed survey procedures. All scales underwent reliability validation (Cronbach's α > 0.83). Ten percent of randomly selected questionnaires underwent third-party audit with discrepancies resolved by a senior researcher. Data entry was performed with two-researcher cross-checking.

Statistical analysis

Statistical analyses were performed using SPSS 24.0 for descriptive statistics (continuous variables expressed as mean ± SD; categorical variables as frequencies and percentages); Pearson correlation analysis examining relationships among RCAC total/subscale scores, PHQ-9, and Fear of Cancer Recurrence Questionnaire (FCRQ) scores; and AMOS 24.0 for structural equation modeling testing the mediation pathway where depression (PHQ-9) influences fear of recurrence (FCRQ) through reproductive concerns (RCAC), with model fit assessed using χ²/df ratio, Root Mean Square Error of Approximation, Comparative Fit Index, Tucker-Lewis Index, and Goodness-of-Fit Index. Indirect effects were estimated via bootstrapping with 5000 resamples generating 95% confidence intervals (CI), and statistical significance was defined as P < 0.05.

RESULTS

Sociodemographic and clinical characteristics

The sample comprised 208 cervical cancer patients of reproductive age (mean age 36.6 ± 5.8 years). Most participants were married (90.4%), Han Chinese (95.2%), and urban residents (59.1%) (Table 1). Notably, 13.9% were nulliparous, while 52.9% had one child. Over two-thirds (70.2%) had cervical squamous carcinoma, and 36.5% were diagnosed at Stage II; the largest proportion across clinical stages.

Table 1 Sociodemographic and clinical characteristics of 208 cervical cancer patients.

Variable		Items	Percentage (%)
Ethnicity	Han	198	95.19
	Others	10	4.81
Residence	Urban	123	59.13
	Rural	85	40.87
Marital status	Single	15	7.21
	Married	188	90.38
	Divorced	5	2.40
No. of children	0	29	13.94
	1	110	52.88
	≥ 2	69	33.17
Education level	Primary/middle	75	36.06
	High school	42	20.19
	College and above	91	43.75
Household income per capita (RMB)	≤ 3000	34	16.35
	3000-5000	67	32.21
	5000-10000	69	33.17
	≥ 10000	38	18.27
Occupation	Employed	136	65.38
	Unemployed/retired	72	34.62
Medical payment method	Medical insurance	152	73.08
	New rural Cooperative Medical Scheme	48	23.08
	Self-pay	8	3.85
Tumor type	Squamous-cell carcinoma	146	70.19
	Adenocarcinoma	35	16.83
	Other types	27	12.98
Clinical stage	I	65	31.25
	II	76	36.54
	III	50	24.04
	IV	17	8.17

Fertility anxiety, depression, and fear of recurrence scores in cervical cancer patients of reproductive age

The total fertility anxiety score of cervical cancer patients of reproductive age was (53.95 ± 7.71), with the highest subscale score in fertility potential (10.97 ± 2.51) and lowest in pregnancy planning (7.05 ± 2.23). The total depression score was (15.84 ± 3.91), indicating moderate to severe depressive symptoms. Total fear of recurrence score was (21.38 ± 4.53), indicating moderate to severe relapse fears (Table 2).

Table 2 Fertility worries, depression, and fear of recurrence scores in 208 cervical cancer patients of childbearing age.

Variable	Items	Score	mean ± SD
Total reproductive concerns	18	18-90	53.95 ± 7.71
FP	3	3-15	10.97 ± 2.51
PP	3	3-15	7.05 ± 2.23
PA	3	3-15	7.87 ± 2.06
PH	3	3-15	10.11 ± 2.59
CH	3	3-15	9.79 ± 2.48
DA	3	3-15	8.16 ± 2.65
Total depression score	9	0-27	15.84 ± 3.91
Total FOR score	7	7-40	21.38 ± 4.53

FOR: Fear of recurrence; FP: Fertility potential; PP: Pregnancy planning; PA: Partner awareness; PH: Personal health; CH: Child health; DA: Disease acceptance.

Analysis of correlation between fertility anxiety, depression, and fear of recurrence in cervical cancer patients of childbearing age

Significant positive correlations were observed: RCAC total score with PHQ-9 (r = 0.48, P < 0.001) and FCRQ (r = 0.43, P < 0.001); PHQ-9 with FCRQ (r = 0.37, P < 0.001). All six RCAC subscales showed similar positive correlations with depression and fear of recurrence (all P < 0.001) (Table 3).

Table 3 Correlation analysis of reproductive concern, depression, and fear of recurrence in cervical cancer patients of childbearing age.

Variable	Relevance	Reproductive concerns							FOR total score
		Total score	FP	PP	PA	PH	CH	DA
Depression score	r	0.477a	0.427a	0.331a	0.526a	0.408a	0.383a	0.492a	0.372
	P value	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001
FOR total score	r	0.426a	0.439a	0.320a	0.452a	0.374a	0.346a	0.417a	-
	P value	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	-

^aP < 0.001.

All correlations are Pearson's r.

FOR: Fear of recurrence; FP: Fertility potential; PP: Pregnancy planning; PA: Partner awareness; PH: Personal health; CH: Child health; DA: Disease acceptance.

Mediating effect of fertility anxiety between depression and fear of recurrence in cervical cancer patients of reproductive age

With depression as the independent variable, fear of recurrence as the dependent variable, and fertility anxiety as the mediator variable, a structural variance model was constructed using AMOS 24.0 software, and parameter estimation and fitting corrections were carried out using the method of great likelihood to construct a structural equation model with fertility anxiety as the mediating effect (Figure 1). The mediation model demonstrated acceptable fit: χ²/df = 2.59, GFI = 0.923, CFI = 0.928, TLI = 0.943, and RMSEA = 0.042. Path coefficients were significant: Depression → reproductive concerns: β = 0.437 (P < 0.001); reproductive concerns → fear of recurrence: Β = 0.348 (P < 0.001); depression → fear of recurrence: Β = 0.389 (P < 0.001); indirect effect (depression → reproductive concern → fear of recurrence) was β = 0.152 (95%CI: 0.112-0.198, P < 0.001), accounting for 28.1% of the total effect.

Figure 1 Mediating effect model of reproductive concerns between depression and fear of recurrence. Solid arrows indicate significant positive paths. Standardized β coefficients are shown next to each arrow. All paths are significant at P < 0.001.

DISCUSSION

Our study found that: (1) Cervical cancer patients of childbearing age exhibited moderate levels of reproductive concern (mean 53.95 ± 7.71), depression (mean 15.84 ± 3.91), and fear of recurrence (mean 21.38 ± 4.53); (2) Reproductive concern positively correlated with depression and fear of recurrence; and (3) Reproductive concern partially mediated the effect of depression on fear of recurrence (28.1% of total effect). Our mediation proportion (28.1%) exceeded the 23.5% reported in breast cancer cohorts[20]. This discrepancy may reflect the specific salience of fertility concerns in cervical cancer, where treatments (e.g., radical hysterectomy, radiotherapy) directly impact reproductive anatomy[2,21]. Regarding depression severity, Jia and Xie[22] reported a PHQ-9 mean of 14.2 in Chinese cervical cancer patients, while our sample showed a higher mean (15.84). This difference may have stemmed from our younger cohort (mean age 36.6 vs 42.1 years) or variations in treatment stages (36.5% Stage II in our study vs 28% in theirs). Notably, reproductive concern scores in our cohort (53.95 ± 7.71) were significantly higher than in breast cancer populations (49.05 ± 15.64)[23], underscoring disease-specific psychological burdens. This is analyzed as follows: (1) Cervical cancer is different compared with other cancers, and the cancer itself and its treatment have a direct impact on the female reproductive organs, which in turn affects reproductive function. With the opening of two-child and three-child policies in China, the fertility requirements of women of childbearing age who have not given birth to any child or have only one child have been rising. However, due to the influence of the disease and the treatment on the fertility function, the patients are prone to depression, anxiety, and other negative emotions, and over time, they have obvious concerns about fertility problems. Fertility problems appear obvious concerns[24]; (2) Influenced by the traditional Chinese concept of passing on the family name to the next generation, society believes that women bear a responsibility and obligation to pregnancy and childbirth, which can cause serious depression in women with cervical cancer of reproductive age, and lead to different degrees of fertility anxiety, so anxiety and depression levels are generally higher[25]; and (3) Women can worry about poor treatment, recurrence and metastasis after treatment[26]. Therefore, clinics should pay attention to the assessment of fertility anxiety, depression and fear of recurrence in patients with cervical cancer of reproductive age, and make timely preventive and treatment programs to effectively reduce the levels of fertility anxiety, depression and fear of recurrence.

The results of this study showed that the total fertility anxiety score and the scores of each dimension were positively correlated with the total depression score and the total fear of recurrence score, and the total fear of recurrence score was positively correlated with the total depression score, which was consistent with the results of the studies conducted by Zhu et al[27] and Wang et al[28]. It indicates that the higher the level of fertility anxiety, the more negative emotions patients produce, the greater the risk of depression, and the more likely they are to worry about disease recurrence and metastasis. Fertility anxiety may, in some cases, bring more stress to reproductive-age cervical cancer patients than the disease itself, often persisting for several years or even throughout a woman's reproductive life[29]. Studies have shown that prolonged fertility anxiety can lead to a range of physical and psychological problems, causing patients to be more prone to depression and fear of recurrence of the disease, which in turn raises the level of fear of cancer recurrence[30]. At the same time, cervical cancer disease itself and treatment modalities such as surgery, chemotherapy, and radiotherapy are a stressor for patients, which can easily lead to adverse psychological emotions, induce depression, and increase patients' worry and fear of disease recurrence. Therefore, healthcare professionals should strengthen psychological counseling for cervical cancer patients of reproductive age in order to soothe patients' adverse emotions and reduce the level of fertility anxiety and fear of recurrence.

This study is the first to establish a formal mediation model (28.10%) linking depression, reproductive concerns, and fear of recurrence in cervical cancer patients. This finding extends beyond prior correlational studies[20,31] by quantifying the intermediary role of reproductive concerns. Fear of recurrence, as a common psychological state in cancer patients, refers to the fear of recurrence, metastasis and progression of cancer in other sites or primary sites, which is manifested by excessive concern about changes in their symptoms, emotional tension and frequent checkups, and is even regarded as a sign of aggravation of the disease when symptoms such as chest tightness and pain occur[32]. In patients with cervical cancer, especially women of reproductive age, this fear is particularly significant and is often closely linked to depression. The results of structural equation modeling showed that depressed mood positively predicted the level of fear of recurrence, which is consistent with the findings of Zhang et al[33]. Cancer, as a life-threatening disease, is a serious stressful event for patients, which can cause post-traumatic stress disorder such as depression and anxiety, leading to uncertainty about treatment effects and prognosis, and worries about daily life, family and finances, which then exacerbate fear of recurrence. For cervical cancer patients in a state of depression, factors such as hair loss that may be caused by chemotherapy, damage to the integrity of the body caused by surgery, and the high cost of treatment all increase fear of recurrence and going through the pain of treatment again, thus aggravating the fear.

However, it is worth noting that fertility anxiety played a key mediating role in this process. The structural equation modeling in this study showed that depressed mood directly predicted fear of recurrence, and by positively predicting fertility anxiety, indirectly influenced the level of fear of recurrence. Qiao et al[34] showed that depressed mood was a significant influence on fertility anxiety. Patients with high levels of depression tend to be self-denying, blame themselves for the problems in their lives, have lower confidence in treatment, and are unable to communicate with healthcare professionals and loved ones in a timely manner in the face of concerns about the impact of the disease on their fertility. Therefore, their negative emotions cannot be effectively resolved, leading to higher levels of fertility anxiety. This kind of fertility anxiety is related to patients' worries about their future fertility, but also aggravates their fear of cancer recurrence.

Fertility anxiety acts as a mediating variable between cervical cancer and worsened reproductive outcomes. Here's how: Cervical cancer is a severe disease. It often causes depression and related adverse psychological emotions, including fertility anxiety. These emotions then interfere with sex hormones and disrupt the hypothalamic-pituitary-ovarian axis function. This interference directly worsens the damaging effects of cervical cancer on the reproductive organs and their function. Cervical cancer patients of reproductive age have greater expectation for fertility, and the decrease or loss of fertility that may be caused by the disease and its treatment undoubtedly increases their level of anxiety. This anxiety directly affects the patient's psychological state, and indirectly exacerbates the level of fear of cancer recurrence through a mediating effect.

Therefore, alleviation of adverse emotions is crucial for improving the psychological status of cervical cancer patients of reproductive age. Wang et al[35] reducing adverse emotions helps to improve patients' attitudes and perceptions of negative events, which reduces the level of fertility anxiety and fear of recurrence. The identification of reproductive concern as a significant mediator suggests that targeted interventions addressing fertility-related distress, such as structured fertility counseling, timely referral to oncofertility specialists, and integrated psychosocial support programs, may concurrently alleviate depressive symptoms and reduce fear of recurrence. This dual-benefit approach is particularly salient for cervical cancer patients, given the direct threat of disease and treatment to reproductive anatomy and function. To translate these findings into clinical practice, randomized controlled trials should test the efficacy of brief, in-hospital fertility preservation counseling in reducing depressive symptoms (PHQ-9) and recurrence anxieties (FCRQ) over 6-month follow-up periods. Embedding such interventions early in the treatment pathway could significantly enhance psychological resilience during survivorship.

This study had several limitations. Its cross-sectional design precludes causal inferences about the observed relationships. Convenience sampling from three regional hospitals limits generalization, particularly for rural populations. Voluntary participation risks self-selection bias-potentially excluding severely distressed patients while over-representing motivated participants. Unmeasured psychosocial confounders (e.g., social support and financial hardship) may influence pathways. Future research should use longitudinal designs tracking reproductive concern trajectories across survivorship phases to establish temporal precedence. Testing similar mediation models in other reproductive-impact cancers (e.g., ovarian cancer) and comparing rural vs urban subgroups would enhance applicability. Most critically, randomized controlled trials evaluating targeted interventions such as brief oncofertility counseling are needed, measuring effects on both depressive symptoms and recurrence fears while controlling for socioeconomic factors.

CONCLUSION

This study is the first to demonstrate that reproductive concerns partially mediate (28.10%) the relationship between depression and fear of recurrence in cervical cancer patients of childbearing age. In cervical cancer patients of childbearing age, reproductive concerns partially explain how depressive symptoms translate into heightened fear of recurrence. Addressing fertility anxiety may be a valuable component of psychosocial care.