The current work is a unique large-scale multi-centre study focusing on the HRQoL of male and female patients with GW using a generic and internationally comparable instrument, the EQ-5D. We found that anxiety and depression posed a major problem for GW patients, and the measurement of VAS suggested that the HRQoL of GW patients was substantially lowered. The current analysis using different preference weights provided a range of utility estimates (overall and characteristic-specific) for future detailed QALY-related cost-effectiveness evaluations. This study also determined the characteristics of patents with relatively lower quality of life, including being female, living in urban areas and suffering multiple GWs, which will be informative for future GW prevention and control efforts.
The research group has published a parallel work conducted as another part of the whole GW project . Both the studies explored the quality of life issue but from different perspectives and each study had its own emphasis. For example, firstly, the current study focused on both males and females, while the previous work mainly assessed female populations. Secondly, the current study was very focused on GW patients only, but the study by Wang et al included women who have a spectrum of HPV-related health statuses or laboratory diagnosis, including normal/abnormal pap smear, cervical precancer, and HPV+/- after abnormal pap, and patients with GW were only one sub-group in the broad analysis . Thirdly, the previous work used a newly-developed HPV-specific instrument, the HPV impact profile (HIP); it is more sensitive and can recognize some slight differences among the targeted HPV-related subgroup women, but it is more difficult to directly compare the findings of the HIP study and other quality of life studies using different instruments. Differently, the EQ-5D, used by the current analysis, is an easy-to-compare HRQoL instrument and commonly-used world widely . Finally, compared to the HIP score outcomes, the EQ-5D index score outcomes reported by the current study were relatively more convertible when taking qualifying quality-adjusted life year (QALY) saved as the study outcome.
The current analysis found that more than half of the GW patients in this survey were suffering anxiety and depression. This is a dramatically high proportion, when compared to the value of < 7% of the sampled general population (aged 15-49 years, by 5-year age group) across mainland China, as a part of the Chinese National Health Services Survey in 2008 (N = 120,703) ; and the proportion is also higher than that of some other countries (~ < 30%, pooled in a previous study by Wang et al)  and a group of GW patients in the UK (24%) . This situation is due mainly to the relatively conservative culture and attitude to sex in China; being diagnosed with sexually transmitted diseases such as GW could be regarded as a big humiliation for patients and they usually would not let other people know and would not receive support even from their families. As expected, we also found that a high proportion of study cases were feeling pain and discomfort (24.7%) when compared to the Chinese general population ( < 10%, in patients aged 15-49 years) . Providing questionnaire interview to part of the patients after their treatment could increase the feeling of pain, but the current study did not distinguish the ordering of treatment and interview. However, discomfort is commonly feeling in GW patients, which could explain some of this detriment. In contrast to the dimension of Anxiety/Depression, the dimensions of Mobility, Self-care and Usual Activities in this GW population are generally less impacted when compared to local and international general populations [15, 17]; this situation is due partly to the reality that most of the studied GW patients (~93%) were younger than 50 years old, and were able to move, to take care of themselves, and to complete their usual activities with no difficulty. Also, the situation of lower rates of any problems in the three dimensions mentioned above is consistent with the findings of a UK GW study .
A large-scale survey included EQ-5D instrument was previously conducted based on a national representative sample in China in 2008, where the average VAS were found to be 80.9 for male and 79.4 for female . Since HRQoL scores are very age-dependent but the subjects of current study mainly aged 15-49 years, we restricted the comparison to narrower age groups (15-49 years, by 5-year age group); it was noted that the national survey reported relatively higher values of VAS score (81.4-89.8 for male, 79.2-89.6 for female). The finding that the mean VAS scores in the current study are lower than those of Chinese general population (65.2 versus ~80 ) suggests that the HRQoL of patients with GW is notably lower than that of the general population. When compared to prior GW studies using EQ-5D in other countries, the mean VAS scores of the current Chinese GW cohort are lower than the estimate of an Australian study (68.9, N = 40) and of a UK study (72, N = 81) [6, 9], but somewhat closer to the estimate of a Canadian study (65.1, N = 39) . The observed differences between these GW cohorts in these settings might be explained by the differences in the VAS scores of the general populations behind them, which are 82.5, 78.7 and 80.1 for the UK, Canada and China, respectively. Based on results from other published works [9, 15, 17], it is not surprising to see that female GW patients had lower VAS scores than male patients. Although a VAS score declining with age was observed in a general population-based survey , our age curve of VAS scores shows a flat pattern, which is consistent with a prior UK GW study . A potential reason for this inconsistency is that the majority of the GW patients were sexually active, and they might have a lower probability of susceptibility to a range of ageing diseases or situations.
Due to the absence of an EQ-5D preference weight set in the Chinese population, three other populations' preference sets were applied to estimate the EQ-5D index scores in the current analysis. Our findings suggest that scores based on the Japanese preference weights could be regarded as the baseline utility values for future cost-effectiveness evaluations, whilst the results based on the UK and US populations could provide a plausible range of utilities estimates for sensitivity analysis. When comparing our EQ-5D index scores to other international GW studies, a wide difference was noted but all our EQ-5D index scores using varied populations preference weights (0.826, 0.843 and 0.859) are within the range (0.76 - 0.91) of the available data from other populations [9–11]; the lowest utility value (0.76) of GW patients was from a Canadian study, and the highest value (0.91) was reported by Myers et al (conference abstract, details unavailable) which has been cited by a number of more recent cost-effectiveness evaluations of quadrivalent HPV vaccine [24–27]. Our EQ-5D index scores analysis also further supports the hypothesis that female patients suffered a larger decrease in quality of life than males and the scores did not differ notably among age groups, as we previously discussed in the VAS scores analysis.
In addition to the variable of gender, other characteristics could also potentially affect the HRQoL of GW patients. Our finding that the urban patients suffered a heavier physiological burden than rural patients could be explained by the urban residents' higher stress from job and mortgage payments and living a faster-paced life. This finding is identical with the results of another HRQoL analysis of HPV-related lesions (including GW) using a HPV-sensitive instrument . It is not surprising to observe that subjects in Southwest China had the lowest score, because a prior survey (N = 2,830) has reported that the general population in Guizhou Province in the Southwest region of China had a relatively low HRQoL (VAS: ~68 - ~ 80 in residents aged 15-49 years) . It is also understandable that more patients with multiple genital warts reported lower scores than patients with only single GW. Although most of the differences detected between subgroups were marginally less than the mean of clinically important differences in EQ-5D (0.074) , they were still within the range (0.011-0.140) , and could potentially generate a relatively significant impact on mass public health intervention programs. As for other variables marginally associated with the HRQoL of GW patients, including initial or recurrent GW, smoking, patient's monthly income and education level, they are beyond the scope of the current discussion, and more research needs to be done.
This analysis has some limitations. Firstly, selection biases could occur in this study, due to the convenient sampling approach we used; we also failed to collect information of non-attended patients and thus could not assess the differences in characteristics between the study participants and those who declined to participate. Secondly, use of the generic EQ-5D instrument, which is not sensitive to HPV-related diseases, potentially underestimates the negative impact from GW and a ceiling effect could occur. Thirdly, the current study is a questionnaire interview-based survey which is usually sensitive to the capacities of the interviewers and quality control, and some of the clinical physicians who administrated the interview had not directly received training provided by CICAMS, and quality-control could potentially vary among study centers to some extent. Another limitation of the study is that we did not have Chinese population specific preference weights and thus could not calculate the EQ-5D index scores accurately. Furthermore, combined with further data related to average duration of a clinical episode and the frequency of recurrence of GW, the detailed utilities findings from the current study would be informative for future cost-effectiveness evaluations related to quality-adjusted life years saved by new interventions against GW.