At the time that the PasQual study was implemented, no published study had simultaneously used several patient-reported outcome instruments in individuals with HPV-related diseases to capture the impact of these diseases from a patient’s perspective. In the PasQual study, a significant negative psychosocial impact was found in women with a range of HPV-related diseases when compared with women with normal cervical cytology. Additionally, HPV-related external genital lesions (VIN2/3 and GW) were found to significantly impair HRQoL.
Differences in the age structure of the study groups reflected the epidemiology of the respective disease. The mean age of women with VIN2/3 was 45 years (range, 21–62 years). This is consistent with the fact that, historically, VIN2/3 and vulval cancer are associated with older age and long-term persistent infection with high-risk HPV, although both are now increasing in incidence in younger women
. By contrast, participants with GW or a history of GW had a mean age of 28 years (ranges, 18–60 and 19–52 years, respectively), reflecting the higher prevalence of GW in young adults than in older individuals
The mean total HIP score for women with normal cervical cytology was 22.3, which was similar to mean total scores reported in the studies of Pirotta et al. (25.8)
 and Wang et al. (28.2)
, and about 8 points higher than that observed in the initial validation study for this instrument (14.4)
. The apparently elevated HIP scores for women with normal cervical cytology may indicate a negative impact of the cervical screening procedure itself, as observed in studies showing that women undergoing routine gynaecological examinations may experience pain or discomfort, embarrassment, fear, worry, nervousness and inconvenience
[42, 43]. However, in the absence of a defined scale linking scores to clinically relevant levels of impact, it is difficult to interpret absolute score values. In our study, women with normal cervical cytology were asked to complete the questionnaire when their test result was received. At this point, they were more likely to feel relieved and less likely to feel anxious than before receiving the result. Consequently, we consider that these women were a suitable reference group for the HIP questionnaire and CSFQ. In the absence of another adequate comparison group, men with a history of GW (non-current) were used as the reference group for men with current GW in analyses of the CSFQ.
Compared with women with normal cervical cytology, sexual functioning was significantly impaired only in women with VIN2/3, as assessed by the CSFQ. This finding may be partly related to age, as women with VIN2/3 tended to be older than participants in the other groups (mean age 44.8 vs 28.0–40.4 years, respectively). However, age is unlikely to be the only factor affecting sexual functioning. Women with VIN2/3 also had a highly impaired health state, as assessed by the EQ-5D index and VAS scores, compared with women in the UK general population, with particular detriments being observed in the anxiety/depression and pain/discomfort dimensions.
Women with current GW experienced the greatest negative psychosocial impact, as measured by the HIP questionnaire, while the impact was generally similar among women with other HPV-related diseases. These observations are consistent with reports of other studies that utilised the HIP questionnaire
[32, 40, 41]. The mean total HIP score for women with current GW was 2.3-fold higher than the score for women with normal cervical cytology, which is consistent with the 1.8–3.7-fold higher scores observed in women with GW versus normal cervical cytology in previous studies
[32, 40, 41]. Dimensions that were particularly affected in women with GW were sexual impact, self-image, and partner issues and transmission. These dimensions have also been previously identified as being of particular concern in women with GW
[40, 44]. Wang et al. observed similar results for sexual impact and self-image, but there was also a substantial impact of GW on worries and concerns and less impact on partner issues and transmission
. It is particularly notable that the impact of GW on psychosocial burden appears to be greater than that of diseases such as VIN2/3, which are considered to be more severe from a clinical perspective and have been shown to have a significant impact on sexual functioning in previous studies
[30, 45]. The high psychosocial impact of GW may be because they are visible and distressing and associated with discomfort and feelings of anxiety, depression, anger, fear of contagiousness, shame and embarrassment
[22, 23, 25, 46]. In addition, treatment of GW is long, painful and often unsatisfactory, with high recurrence rates
As assessed by the EQ-5D, participants with GW reported problems with anxiety/depression more frequently than the UK general population. This is consistent with current knowledge regarding the experience of individuals with GW in whom much of the associated morbidity is psychological in nature
. By contrast, a lower proportion of participants with GW in our study reported problems with mobility and usual activities than the UK general population. This latter observation is likely to be due to the age difference between the two populations as participants with GW were younger overall than the UK general population. The observed impact on the anxiety/depression dimension (41% of participants with GW reported problems) is similar to that reported in the recent study of Woodhall et al.
, in which 37% of participants with GW reported problems in this dimension, and consistent with the findings of other studies
[20, 22, 23]. However, contrary to our observations, three of these studies reported an increased level of pain/discomfort
[22–24] and one study reported a detrimental impact on usual activities
 among individuals with GW when compared with general population samples.
Overall, participants with GW had a slightly impaired health state, as assessed by the EQ VAS only, compared with the UK general population. However, when focussing on young adults (18–34 years of age), in whom the prevalence of GW is the highest, both the mean EQ-5D index and VAS scores were significantly reduced compared with the UK population norms. In our study, the weighted mean EQ-5D index and VAS scores for participants with GW were 0.90 and 78, respectively, which are similar to those reported for the recent study of Woodhall et al. (0.87 and 77, respectively)
. A significant reduction in health state based on EQ-5D index and VAS scores in individuals with GW when compared with general population values has been reported in other studies
[22, 23], in which the average reductions in EQ-5D index score were 3.9 and 9.9 percentage points, respectively, and the average reductions in VAS scores were 13.9 and 6.0 percentage points, respectively.
Participants with current GW had a significantly impaired HRQoL, as assessed by CECA scores, compared with participants with a history of GW (non-current). A similar but lesser impact of GW on HRQoL has been demonstrated in men in a study using the initial 22-item CECA questionnaire
. When stratified by sex in the present study, the difference between GW and history of GW continued to be observed in women, but not in men. In the PasQual study, female participants with GW had significantly lower scores for the sexual domain of the CECA than those with a history of GW, whereas sexual functioning as assessed by the CSFQ was similar between participants with GW and a history of GW. This may seem contradictory, but it is important to note that whilst the CECA evaluates the psychological aspects of sexual life specifically related to GW, the CSFQ is a generic instrument that evaluates functional aspects of sexual life, which may explain these differences.
Despite several measures taken to try and increase study recruitment (e.g. extension of study period and reminders sent to participants), sample sizes were lower than planned in some groups in our study. For participants with borderline nuclear abnormalities and/or mild dyskaryosis, CIN1 and a history of GW, actual sample sizes were 23, 84 and 62 respectively, compared with the 200 planned for each group. Several reasons may explain the low numbers, including that many women screened for participation in the CIN1 group did not have histological confirmation of CIN1 and were therefore not included, in the other two groups, few individuals complied with the retrospective recruitment process and, in addition, individuals with a history of GW recruited prospectively often had other STIs, which was an exclusion criterion.
As each HPV-related disease is associated with specific demographic characteristics, the UK general population may not have been the best comparator to evaluate the representativeness of our study population with regard to each specific disease. Differences in the mean age between different HPV disease groups may have partially impacted comparison across groups, particularly for sexual functioning. The older age of the VIN2/3 group compared with other groups may have impacted the comparison of sexual functioning assessed by the CSFQ. Furthermore, the younger age of the GW group compared with the reference group could have masked a potential negative impact of GW on sexual functioning. For the CECA, participants with a history of GW were used as the reference group. Although this is not without limitations, we considered it to be the most appropriate comparator group as the CECA cannot be administered to individuals who have never experienced GW. The validation study for the CECA compared individuals with an initial diagnosis of GW with a group of individuals with persistent GW who were not receiving current treatment
. Furthermore, factors such as the number and size of lesions, which were measured in the validation study
, were not considered in the current study. Finally, the study did not aim to collect clinical data. Thus, while we observed statistical differences in psychosocial burden and HRQoL between HPV disease groups, we could not assess the extent to which these differences were clinically meaningful.