Measuring health-related quality of life in cervical cancer patients: a systematic review of the most used questionnaires and their validity

Treatment of the fourth most common cancer in women, cervical cancer, consists of either surgery and/or (chemo-)radiotherapy, based on the FIGO stage of the disease [1, 2]. Depending on the treatment, different side effects, such as: bladder, bowel, and vaginal dysfunction, lymphedema, and lymphocysts can occur [3, 4]. These side effects, together with the emotional and social impact of the disease, influence a patients’ health-related quality of life (HRQoL), even when survival is extended. The acceptance of medical treatments is critically dependent on these HRQoL consequences, making it one of the most important parameters in the evaluation of medical treatments.

Quality of life is a complex, multidimensional construct, with a range of conceptual definitions and is often evaluated using HRQoL tools. There is general agreement that multidimensional HRQoL assessment should at least include physical, social and psychological/emotional functioning and well-being [5]. The validity and suitability of such HRQoL tools, is represented by their psychometric properties. Psychometric properties indicate if a measurement tool is; free of error (reliability), assesses what it is intended to measure (validity), is able to detect change in an individual over time (responsiveness), and the degree to which one can assign qualitative meaning to quantitative scores (interpretability) [6]. Using an instrument with (good) psychometric properties that have been evaluated enables the user to draw more robust and substantial conclusions. Since the psychometric properties of a measurement tool can differ per target population, it is recommended that they are evaluated in that specific target population.

Others have studied the psychometrics and appropriateness of HRQoL tools in gynaecologic oncology in general [7‐9]. However, both a clear overview of the available disease specific HRQoL tools for cervical cancer patients and an appraisal of their psychometric properties are lacking. Vistad et al [10] reported on the impact of cervical cancer on HRQoL, and critically appraised a number of studies regarding HRQoL measurement in this population. However, they did not report or evaluate the psychometric properties of the HRQoL instruments for cervical cancer. Furthermore, FIGO stage is important in the treatment of cervical cancer, and can result in different side effects influencing relevant aspects of HRQoL [2‐4, 11]. As such, the validity, reliability, and responsiveness of an HRQoL tool can differ per disease stage. For a valid and patient-centered evaluation of health status, it is important that the HRQoL tool measures aspects of health status that are important to patients with cervical cancer, and that the measurement characteristics are adequate for the specific patient population. Thus, we hypothesized that cervical cancer-specific HRQoL tools will provide the most valid and patient-centered evaluation of health status.

The aim of this study therefore is to provide an overview of the used HRQoL tools in cervical cancer patients, to identify cervical cancer specific HRQoL tools and to assess their psychometric properties. This allows for an evidence based choice of a cervical cancer specific HRQoL tool in both clinical practice and clinical trials.

Figure 1 provides an overview of the literature search and study selection. Our literature search yielded 2184 unique records, of which 320 remained after screening titles and abstracts. The full-text of these studies was reviewed for eligibility. Studies were excluded for the following reasons: not including an HRQoL assessment (89), duplicates (23), non-cervical cancer patients (21), validation study (13), review (12), a cost-effectiveness study (4), and no full text copy of the questionnaire available (2). This yielded 156 studies (20,690 patients) using 31 different HRQoL tools. See Additional file 5 with the supplemental references for a list of all included studies and their respective reference number, with the prefix ‘s’.

The FACT-Cx and EORTC QLQ-CX24 were the identified cervical cancer-specific HRQoL tools, which were used in 22 and 35 out of 156 studies, respectively. The EORTC QLQ-CX24 appears to be the most used and a more appropriate tool to assess HRQoL in cervical cancer patients. However, its validity is uncertain since 5 out of 9 psychometric properties are doubtful or not reported in current literature. For example, no correlation was found between the performance of the tool and a reference standard, the minimal important change that should be detected was not defined, and floor and ceiling effects were not reported. The validity of the FACT- Cx is even more uncertain as 7 out of the 9 psychometric properties were doubtful or not reported at all. Similar problems as with the EORTC were reported; there was no correlation found between the performance of the tool and a reference standard, the minimal important change that should be detected was not defined, and floor and ceiling effects were not reported. But for the FACT-Cx there was also no description on how the questionnaire and its items were selected, hypotheses regarding the scores were not confirmed, and it remained unclear if repeated measurements over a longer period of time can detect a (relevant) change in quality of life.

Thus the EORTC QLQ-CX24 has been more thoroughly assessed regarding its psychometric properties and scored better (both regarding the number of positively rated psychometric properties and the score per psychometric property) when compared to the FACT-Cx.

To our knowledge, this is the first systematic review that identified different HRQoL tools that have been used to assess quality of life in patients with cervical cancer. We used the COSMIN checklist for a thorough evaluation of the quality of the two cervical cancer specific HRQoL tools. We have provided evidence that the EORTC QLQ-CX24 is the most appropriate and valid cervical cancer-specific HRQoL for a patient-centered evaluation of health status of cervical cancer patients in general.

Our study has a few limitations. First, one possible HRQoL tool, the SES-QOL, could not be included as there was no full text copy of the tool available. Despite repeated requests, we did not receive a full text copy and had to exclude this tool from our results as we could not assess whether it meets the HRQoL definition. On the other hand, as the SES-QOL is not a cervical cancer specific HRQoL tool it would not have influenced our final conclusion.

Second, almost all psychometric properties highly depend on methods and design of the validation study. For instance, a property such as construct validity could score positively if only one hypothesis was tested and confirmed (>75% confirmed), while rated negatively when another hypotheses was tested but rejected (<75% confirmed). Thus the rating of an HRQoL tools’ validity could therefore also be a representation of the validation study design, instead of the actual validity. Regardless, the uncertainty surrounding the validity of cervical cancer-specific HRQoL tools remains, and more evidence is needed to reduce this uncertainty.

Do note that the scoring model that we applied cannot be used to calculate an ‘overall’ score as the weight of each individual psychometric property can differ per specific design, application and/or study population, e.g. construct validity, reliability for discriminating between different (sub)groups, and responsiveness for the evaluation of treatment effects [12]. Thus, an external comparison on validity across HRQoL tools is only possible per psychometric property and not on an ‘overall’ score.

Third, the psychometric properties in the identified studies were often not reported, incorrect or unclear, and the terminology and definitions differed from those proposed by Terwee et al [12]. Regardless, this is the most up-to-date overview of current available literature and it should be noted that the absence of evidence on the above mentioned psychometric properties, either due to no reported data or inappropriate design/methods, is not to be confused with evidence of their absence.

Based on our results, the use of only a cervical cancer-specific HRQoL tool is not preferred since its validity remains to be proven. We therefore recommend to always use a well-validated generic HRQoL tool to be able to ascertain the most valid and patient-centered evaluation of health status, both in clinical practice and clinical trials. In addition, by using already well-validated generic HRQoL tools in combination with one of the cervical cancer-specific tools, researchers will be able to properly assess the psychometric properties of the FACT-Cx and EORTC QLQ-CX24. Another option could be to develop a new and more valid HRQoL tool. However, this may be redundant as there remains uncertainty regarding the validity of already available HRQoL tools and the absence of evidence on their validity should not to be confused with evidence of absent valid tools. For both the validation of current HRQoL tools and development of a new tool, we would recommend to use an established protocol, such as the quality criteria presented by Terwee et al [12]. A data presentation with an assessment of psychometric properties for both early and advanced stage cervical cancer is warranted as their treatment and subsequent possible side effects differ distinctively [14‐21].

The validity of the often used EORTC QLQ-CX24 questionnaire for cervical cancer patients remains uncertain since 5 out of 9 psychometric properties were doubtful or not reported in current literature. Cervical cancer specific HRQoL tools should therefore always be used in conjunction with validated generic cancer HRQoL tools until proper validity has been proven, or a more valid tool has been developed.