Impact of cervical cancer on quality of life of women in Hubei, China

We aimed to assess the quality of life (QOL) of the patients with cervical cancer after initial treatment, the factors affecting QOL and their clinical relevance. A total of 256 patients with cervical cancer who visited Zhongnan Hospital of Wuhan University from January 2017 to December 2017 were enrolled in this study. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30) and cervical cancer module (EORTC QLQ-CX24) was used to assess the QOL of patients. More than half of the patients with cervical cancer reported an excellent QOL. Symptoms mostly experienced were insomnia, constipation, financial difficulties, and menopausal symptoms. Global QOL and social functioning were statistically associated with education level, occupation, the area of living, family income and treatment modality. Similarly, role functioning showed significant association with the stage of cancer, treatment modality and time since diagnosis. The rural area of living and poor economic status of the patients with cervical cancer has a negative impact on overall quality of life. Younger and educated patients are more worried about sexuality. Patients treated with multiple therapies had more problems with their QOL scales than patients treated with surgery only.


Materials and Methods
Study design and participants. A descriptive cross-sectional study was conducted after approval by the institutional review board of Zhongnan Hospital of Wuhan University, Department of Gynecological Oncology, Wuhan, Hubei, China. We obtained written informed consent from all the participants. All methods in this study were performed by the relevant guidelines and regulations. A total of 256 patients with CC who visited Zhongnan Hospital from January 2017 to December 2017 and who met the eligibility criteria enrolled in this study. Women with any stage of CC including recurrence (FIGO stage I, II, III and IV), able to understand Chinese and willing to participate in this study were included. Women who declined or who refused to cooperate and patients with psychiatric co-morbidity, communication disorders and or severe other medical condition were excluded from this study.
Treatment guideline for cervical cancer in Zhongnan Hospital is as follows: i) early stage cervical cancer (IA-IIA2) is treated by either surgery and or radiotherapy; ii) advanced stage cervical cancer (IIB -IVA) is treated by primary chemoradiation. However, selected patients with stage IIB are treated with neoadjuvant therapy. Metastatic disease (IVB) primarily treated with chemotherapy. Indications for surgery combined with adjuvant treatment are the presence of one or more pathologic risk factors. Those risk factors are >1/3 stromal invasion, LVSI, and tumor size (i.e., Sedlis criteria) as well as tumor histology of adenocarcinoma and close or positive surgical margins as per National Comprehensive Cancer Network (NCCN) guideline 11 . Measurements. The survey instrument consisted of four parts. The first section included demographic information of women, which was collected by interviewing the participant with a structured questionnaire. The second section consisted of clinical characteristics, and it was obtained by reviewing the medical records. The third section was the validated Chinese version of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30) and EORTC QLQ-CX24 (Cervical cancer module) [12][13][14] . The EORTC questionnaire has been widely employed and tested in different studies among the various cultural group and demonstrated acceptable validity 13,[15][16][17][18][19][20][21] . The EORTC QLQ-CX24 was selected to assess the QOL of CC patients as it is the most appropriate and valid health-related quality of life cervical cancer specific tool for self-reported evaluation of health status among them 22 . The Chinese version of the EORTC QLQ-CX24 was validated among Chinese cervical cancer patients and reported as a reliable and efficient instrument in clinical research to study QOL 13,21 .
The EORTC QLQ-C30 incorporates five functioning domains (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), global health and overall QOL scales and six single items that assess additional symptoms commonly reported by cancer patients (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) along with perceived financial difficulties 12 . The EORTC QLQ-CX24 includes 24 items consisting of three multi-item scales (symptom experience, body image, and sexual/ vaginal functioning scale) and six single-item scales 15 . In the present study, the reliability coefficient for EORTC QLQ-C30 and EORTC QLQ-CX24 was 0.830 and 0.801 respectively.
All scores on the EORTC QLQ-C30 and QLQ-CX24 were transformed into 0 to 100 scale according to the EORTC QLQ scoring manual 23 . Higher scores in GHS and functioning scale represent better levels of functioning and worse levels of symptoms in symptom scales. For EORTC QLQ-CX24, higher scores indicate more symptoms/problems. For the scales sexual activity and sexual enjoyment, a higher score means fewer problems or proper functioning 24 . Statistical analysis. For statistical analysis, SPSS (version 16.0) was used. Each scale of EORTC QLQ-C30 and QLQ-CX24 based on QOL scores were dichotomized into problematic and non-problematic. The problematic group was defined as one with a global QOL or a functioning score of 33 or less or with a symptom score of more than 66 23,25 .
Normality tests were carried out for the Global Health Status (GHS), the Functioning Scale, and the Symptom Scale. Data were analyzed with non-parametric tests namely Mann Whitney U test and Kruskal Wallis tests. The patients were divided into groups according to age (<45 years, >46 years), education (illiterate, literate), residence (rural, urban), stage (I, II, III, IV), and treatment modality (surgery only, surgery + radiotherapy + chemotherapy, radiotherapy and or chemotherapy). Multivariable linear regression was performed to explore associations between overall QOL (GHS) and patient and treatment-related variables. A value of P < 0.05 was considered to indicate statistical significance. Clinical relevance was tested to determine statistically significant results regarding (difference of >10 Points) 26 .

Results
Sample characteristics. A total of 256 patients with CC were enrolled in the study. The mean age of the patients was 53.4 ± 10.5 years. Almost 44% of the patients reported annual family income less than 1450 (USD). The proportion of patients in FIGO stage I, II, III, and IV were 40.2%, 46.5%, 7.8% and 5.5% respectively. Around 54% of patients had surgery combined with chemo-radiotherapy (Table S1). QOL Score. More  and peripheral neuropathy were more problematic among the age group of over 46 years. Dyspnea (p = 0.000), and sexual worry (p = 0.002) were significant among the patients under 45 years (Table 2).
Occupation. Service holder showed good global QOL. However, retired/unemployed/housewife group of patients had good social functioning (p = 0.000, clinically relevant) ( Table 3).

Stage of cancer.
Time since diagnosis. Patients with 5 to 10 years of survival reported good global QOL, physical, role, social and sexual and vagina functioning (p < 0.05, clinically relevant). However, most symptoms, pain (p = 0.006, clinically relevant), nausea/vomiting (p = 0.003, clinically relevant) and appetite loss (p = 0.015, clinically relevant), were experienced within 12 months. Patients who were diagnosed more than ten years reported more fatigue (p = 0.045, clinically relevant) and constipation (p = 0.041, clinically relevant) symptoms (Fig. 1).
Multiple linear regressions. Table 5 presents the association between overall QOL and different variables related to patient and treatment. It shows that lower family income, the rural area of living had a negative impact on the overall QOL, and the advanced stage of cancer had a statistically significant effect on overall QOL of patients (Table 5).

Discussion
The characteristics of patients with CC and QOL after treatment was the focus of this study. More than half of the patients with CC reported an excellent QOL, similar to the most published data 21,27  Patient's lower annual family income and rural area of living showed a negative impact on global QOL. Reports indicate that less education had been associated with limited knowledge about health issues and poor health 10,21 . Cancer survivors living in the rural area are at higher risk for a variety of poor health outcomes 29 and poor socioeconomic status (e.g., lower education level and income) are less likely to have follow-up care with providers leading to poor health outcome 27,30 . Patients from a rural area or with lower economic status or illiterate people might be unaware of cervical cancer. So, these individuals may usually reach the hospital with the late stage of cancer, which leads to poor treatment outcome and consequently a reduced quality of life. Therefore, these problems should be given due attention by the concerned authority to improve the QOL.
Younger patients reported better functional scales than older age groups which are similar to the study result reported by the Action Study Group 27 . Wenzel et al. reported that younger CC patients experience a persistent detrimental effect on their QOL 31 . Several studies reported a negative impact of sexuality across all CC patients 24,[32][33][34] . Young patients in our study had reported more sexual worry compared to an older group of patients. In line with our study, the previous research said younger patients were concerned with fertility, femininity, treatment-related menopause, and relationship issues 35 . Cervical cancer is known as the human papillomavirus (HPV) related cancer, and a positive high-risk HPV regarded as a sexually transmitted infection (STI). Young people are sexually active, so the chances of having STI is also higher among those who have risky sexual behavior; on the other hand, they have access to the information about STI or HPV which might be partially correct. Therefore, many young women especially the educated patients might blame their husband or partner for the disease, which leads to relationship problems and causes more sexual worry. Many studies reported a negative impact on sexuality among patients with CC and its treatment 21,34,36 . These findings underline the importance of counseling regarding these problems, especially with younger and educated patients about the right information of high-risk HPV infection and the existence of all other co-factors as well.
Sexuality is an essential aspect of gynecological cancer, thus being a crucial determinant of QOL. In the present study, there was a significant decrease in sexual enjoyment and the sexual and vaginal functioning score. Previous reports also stated that 40% to 100% of individuals face sexual dysfunction after treatments because CC and its treatment affect the same areas of the body that are involved in sexual response 10,37 . Patients with surgery along with chemotherapy and radiotherapy reported worse in sexual and vaginal functioning than those with surgery. Sexual dysfunction from surgery is mainly due to the shortened vagina, vaginal dryness, decreased libido 38,39 . However, after radiotherapy, sexual dysfunction is caused by vaginal stenosis which leads to dyspareunia, difficulty in orgasm, a decrease in sexual satisfaction, and changes in body image 40 . Patients who had undergone radiotherapy and chemotherapy had experienced more symptoms like fatigue, nausea and vomiting, pain, appetite loss, constipation, diarrhea and financial difficulty than those who underwent surgery only. Many studies have mentioned that radiotherapy to the pelvic cavity has easily caused intestinal dysfunctions 41 . Radiation has also created lactose and bile salt malabsorption, intestinal bacteria imbalance and altered intestinal peristalsis. Therefore, radiotherapy for CC often causes intestinal dysfunctions 42,43 .
The advanced stage of cancer showed a negative impact on global QOL and patients with early-stage cancer reported better QOL. Several studies reported that, for global health status or overall QOL, patients with stage I, II, and III of cancer have higher QOL compared to stage IV 10,44 . Regarding role functioning, patients in stage I had the better QOL followed by stage II; stage IV had the worse role functioning. Patients at the late stage of cancer would have poor role functioning as these patients usually planned for palliative management and therefore unable to perform much work.
Also, time since diagnosis affects the self-reported health status and QOL among cancer survivors 9 . The present study findings are consistent that time is a significant factor in QOL of survivors. Patients diagnosed for 5 to 10 years reported higher scores on global QOL, physical functioning, role functioning and sexual and vaginal functioning. However, after ten years since diagnosis, the functional scale (global QoL, physical, role, social and sexual and vaginal functioning) scores were decreasing than in the 5-10 years' period and also nearly similar to the time of 6-12 months after diagnosis. Similarly, fatigue, nausea and vomiting, pain and constipation symptoms were increased with more than ten years of survivorship. These findings could be the result of the long-term effect of chemotherapy and radiotherapy that patients experience bowel, bladder, and sexual dysfunction even after many years of treatment is in line with another study 45 Table 4. Quality of life score according to the stage of cervical cancer and treatment modalities. *Clinical relevance ≥10 points differences; S + C + R: surgery + chemotherapy + radiotherapy; C/R: chemotherapy and or radiotherapy.
health outcome. This finding suggests that the QOL of the patient is changing over the long term. Further study is recommended to evaluate the QOL of long-term survivors. Nevertheless, this study has some limitations. The QOL of cancer survivors changes over time. As this is a cross-sectional design, the assessment of QOL was not done over time, and the lack of the comparison of QOL score before and after treatment contribute to the limitations. The data collection was limited to a single institution based so the study results could not be generalized to the whole population of cancer survivors in China. However, the study contributes to how to improve patient care and further research for women with CC in China. Longitudinal and intervention studies with control group may better evaluate the QOL of CC survivors.

Conclusion
More than half of the patients with cervical cancer reported an excellent QOL. The rural area of living and poor economic status of the patients with cervical cancer has a negative impact on overall quality of life. Younger and educated patients are more worried about sexuality and patients treated with multiple therapies had more problems with their QOL scales than patients treated with surgery only.