Original research article
Impact of genital warts on emotional and sexual well-being differs by gender
International Journal of STD & AIDS 2014, Vol. 25(13) 949–955 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462414526706 std.sagepub.com
Henrike J Vriend1,2, Pythia T Nieuwkerk3 and Marianne AB van der Sande1,4
Abstract To assess gender-specific impact of genital warts on health-related quality of life (HRQoL), and to explore to what extent sexual characteristics and clinical symptoms influenced the impact on emotional and sexual well-being of both sexes. We conducted a survey of sexual and clinical characteristics from persons diagnosed with genital warts at STI clinics. HRQoL was measured using two measurement tools: 1) the generic EQ-5D; and 2) the genital warts-specific CECA-10 including an emotional well-being and a sexual activity dimension. The EQ-5D scores were compared with scores of the general population. Descriptive analyses were used to explore characteristics associated with HRQoL scores stratified for gender. The HRQoL-measurement tools showed that genital warts have especially an emotional impact. The impact of genital warts on HRQoL was greater for women than for men. In addition, the CECA-10 showed that in women the impact of genital warts on sexual activity was influenced by age, relationship status and number of warts. No related factors were seen in men. Genital warts have a greater impact on women than on men. In women, sexual and clinical factors influenced the impact of genital warts on well-being, whereas in men no such factors were found.
Keywords Sexually transmitted infection, genital warts, condylomata acuminata, human papillomavirus, HPV, impact, psychosexual, quality of life Date received: 26 September 2013; accepted: 11 February 2014
Introduction Genital warts are common among sexually active persons and are caused by the human papillomavirus (HPV), a virus which is sexually transmitted. In the Netherlands, the number of episodes of genital warts diagnosed at general practices doubled in a 10-year period, from 74 per 100,000 population in 2002 to 144 per 100,000 population in 2011.1 Although symptoms are in general mild, decreased emotional wellbeing has been reported among persons with genital warts compared to persons without genital warts.2–5 The well-being of a person can be expressed in terms of health-related quality of life (HRQoL). HRQoL is generally defined as a subjective and multidimensional construct encompassing a persons’ physical, emotional and social functioning, which can be affected by a medical condition and/or its subsequent therapy.6 Receiving an HPV diagnosis was previously shown to have a negative impact on HRQoL, which was the result of emotional distress caused by anxiety and fear.7 A persistent
HPV infection can result in (pre)malignant lesions or cause anogenital warts. Having these clinical outcomes could significantly reduce the HRQoL of HPV-infected persons. The overall impact of these outcomes will depend on the severity of symptoms. For example, when a woman is informed by her physician of having an abnormal smear result representing a high-grade 1 Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands 2 Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Netherlands 3 Department of Medical Psychology, Academic Medical Center, Amsterdam, the Netherlands 4 Julius Center, University Medical Center, Utrecht, the Netherlands
Corresponding author: Henrike J Vriend, National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, P.O. Box 1, 3720 BA Bilthoven, the Netherlands. Email: [email protected]
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squamous intraepithelial lesion (HSIL), this will have a more negative impact on HRQoL than being informed of having an abnormal smear representing a low-grade squamous intraepithelial lesion (LSIL).8 Similarly, having large genital warts versus small genital warts could impact HRQoL differently. In addition to the differences in clinical symptoms of genital warts, it is important to keep in mind differences in persons’ characteristics since the impact of having genital warts on a persons’ HRQoL seemed to differ between genders, women reporting lower HRQoL scores than men.2,4,5 Whether women experience more discomfort from genital warts or that these differences between genders are caused by differences in sexual characteristics or clinical symptoms of genital warts is unknown. Insight in the impact of the different clinical manifestations caused by HPV on HRQoL is important for decision-making about which vaccine to use to prevent HPV infection: the vaccine protecting against cervical cancer (CervarixÕ ) or the vaccine protecting against cervical cancer as well as genital warts (GardasilÕ ). As HRQoL is necessary for cost-effectiveness studies, it is important to delve deeper in determinants of among others the differences in HRQoL between male and female genital warts patients. This information about differences in gender is especially important since current cost-effectiveness studies are not limited to assess the impact of vaccinating women only but are also focusing on exploring the impact of vaccinating boys as well. If the HRQoL of male genital warts patients is less affected by genital warts than the HRQoL of female patients, this can have important influences on the cost-effectiveness of implementing HPV vaccination for men. Therefore, we here explored if there are certain factors that have a significantly different impact on the HRQoL of female genital warts patients than on the HRQoL of male genital warts patients, and if any such gender difference in HRQoL can be explained by a difference in sexual characteristics and/or clinical symptoms of genital warts.
Methods Between February and August 2012, attendees of 9 STI clinics across the Netherlands were asked, at the moment a first or recurrent episode of genital warts was detected, to participate in the study. Characteristics of the wart(s) (i.e. number of genital warts, size of the biggest wart, anatomical location, first or recurrent episode) were documented by a physician. At the end of the visit a questionnaire was filled out by the participant, covering sexual behaviour, history of genital warts and HRQoL.
HRQoL measurement The impact of genital warts on HRQoL was measured using a generic and a condition-specific measurement tool. The EQ-5D, which stands for European Quality of Life, is a generic HRQoL instrument that has previously been used in a wide range of clinical areas (http:// www.euroqol.org).9 The EQ-5D consists of a descriptive part in which the patient indicated the level of problems (three levels: no problems, some problems, severe problems) on five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D also includes a visual analogue scale (EQ-VAS) which was used to rate their overall state of health on the day of questionnaire administration (0 is the worst and 100 the best imaginable health state). In addition, we used the genital wart-specific CECA-10 (CECA is a Spanish acronym of Specific Questionnaire for Condylomata Acuminata). This questionnaire was previously shown to be a valid measure of HRQoL among persons with genital warts.10 The CECA-10 consists of 10 statements regarding the impact of genital warts on an emotional dimension (6 statements, CECA-6) and a sexual activity dimension (4 statements, CECA-4) (Table 1).3 Participants indicated on a five-point scale how often they experienced the specific statement (always to never). To facilitate interpretation and comprehension of the CECA scores all dimensions were standardised for a scoring between 0 (worst HRQoL) and 100 (best HRQoL). Table 1. Description of the CECA questionnaire. Item Emotional dimension 1. I am afraid that the lesions won’t disappear 2. I am anxious to know whether I am going to recover from the infection for good 3. I worry about whether the warts will get worse or if there will be some complications 4. My state of mind is upset (anxiety, depression, sadness, uneasiness. . .) 5. I feel more insecure 6. Knowing that I have the illness affects me in my daily life Sexual dimension 7. My sexual drive has decreased 8. I feel worried during the act 9. I avoid sexual relations 10. My sexual relations have decreased in quality and/or frequency CECA: Spanish acronym of Specific Questionnaire for Condylomata Acuminata. Each question allows an answer on a five-option Likert scale: ‘‘always’’ ¼ 1, ‘‘almost always’’ ¼ 2, ‘‘sometimes’’ ¼ 3, ‘‘rarely’’ ¼ 4, ‘‘never’’ ¼ 5 (items 1 and 3 also allowed the option of ‘‘not applicable’’ scored as ‘‘never’’ ¼ 5).
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Descriptive analyses To evaluate the impact of genital warts on HRQoL, we first compared EQ-5D scores per dimension to EQ-5D scores of 9685 men and women recruited in 2000–2002 at 104 general practices (GPs) across the Netherlands.11 The selection of GPs was based on region, level of urbanisation and practice type (solo or group). Within a GP, 5% of the patients registered were randomly selected, of which on average 64.5% responded. Cases and controls were matched on gender and age group. We did not have information about sexual preference in the GP control dataset, therefore we used men in general for both heterosexual men and MSM in our study population. Additionally, mean CECA scores and 95% confidence intervals (CIs) were given for women, heterosexual men, and MSM separately and tested for significance (p < 0.05) using one-way analysis of variance (ANOVA). Mean emotional and sexual CECA scores were also tested for significant differences between the categories of the independent variables (i.e. sexual characteristics and clinical symptoms) using ANOVA. Correlation coefficients and p values were estimated for continuous variables (i.e. age and number of warts). Due to small numbers of MSM, we did not show mean CECA scores per variable for this subgroup. The population included six male clients of sex workers. Since they have different sexual behaviour in comparison to other men, they are to be expected to score differently on the HRQoL measurement tools. Unfortunately, the group was too small for proper analyses and therefore this group was excluded.
Results Characteristics study population A questionnaire on sexual behaviour, genital warts history, and HRQoL, as well as a questionnaire with clinical symptoms, were available for 104 persons diagnosed with genital warts: 50 women, 38 heterosexual men, and 16 MSM. The median age of women was 22 years (interquartile range [IQR]: 20–24 years), of men 24 years (IQR: 23–29 years), and of MSM 27 years (IQR: 22–45 years). The ages ranged from 17 to 51 years among women, 22 to 53 among heterosexual men, and 20 to 71 among MSM. The median number of sexual partners in the last 6 months was similar between women and heterosexual men, although the IQR for heterosexual men was 1–4 partners and for women 1– 3. MSM reported more sexual partners in the past 6 months, median number of 3 (IQR: 2–6). Clinical symptoms showed that on average women were diagnosed with more warts than the men were (median 4.5
versus 3 warts, respectively). However, men were more often diagnosed with warts larger than 0.5 centimetre (24% of heterosexual men and 19% of MSM versus 16% of women). In addition, MSM most often had a recurrent episode, followed by heterosexual men and women (31%, 18%, and 8%, respectively).
EQ-5D scores The EQ-5D was completed by 49 women, 37 heterosexual men, and 16 MSM. For all dimensions, with exception of self-care, women reported more problems than men did (Figure 1). Men with genital warts reported fewer problems on the EQ-5D than controls except for the dimension of anxiety and depression. Among women with genital warts smaller differences with controls were noted for mobility and pain/discomfort than observed among men, but larger differences were seen for anxiety/depression. Of the participants completing the EQ-5D, 45 women, 34 heterosexual men, and 14 MSM also filled in the EQ-VAS. On the EQ-VAS women rated their current health state lower than men: 75.3 (95% CI: 70.3–80.2) for women compared to 83.7 (95% CI: 79.3–88.2) for heterosexual men and 82.1 (95%CI: 75.4–88.9) for MSM.
CECA-10 scores The emotional dimension (CECA-6) of the genital warts-specific HRQoL tool was completed by 49 women, 37 heterosexual men, and 16 MSM. The sexual activity dimension (CECA-4) was completed by 44 women, 38 heterosexual men, and 15 MSM. A mean score for the CECA-6 and CECA-4 of 60.9 (95% CI: 54.4–67.5) and 71.5 (95% CI: 63.5–79.6), respectively, was observed in heterosexual men and of 48.4 (95% CI: 42.3–54.4) and 55.7 (95% CI: 48.3–63.0), respectively, in women. These differences between women and heterosexual men were significant. MSM had higher emotional scores than heterosexual men (70.1 [95% CI: 57.4–82.7]), but scored similar on the sexual activity dimension (70.8 [95% CI: 54.5–87.2]). MSM did not significantly differ from heterosexual men. In addition, we calculated the mean CECA scores with the 95% CIs per patient characteristic stratified by women and heterosexual men (Table 2). For this analysis, we excluded MSM since numbers were too small for meaningful analysis. None of the variables within the CECA-6 contained mean scores that differed significantly from each other. However, within the CECA-4 significant differences in mean scores were found in women. Women at young age (15–19 years) compared to older age (20–29 years), women with no partner compared to women with a steady partner, and
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40 35 30 25 20 15 10
Mobility
Self-care
Usual activities
case
Pain/ discomfort
MSM
men
women
MSM
men
women
MSM
men
women
MSM
men
women
MSM
0
men
5 women
% reporting some or severe problems
952
Anxiety/ depression
control
Figure 1. Per cent of persons with genital warts ( ¼ cases) in comparison to controls representing the general Dutch population* reporting some or severe problems per dimension of the EQ-5D and 95% confidence interval (CI), by women (n ¼ 49), heterosexual men (n ¼ 37), and MSM (n ¼ 16). * Controls are based on 9685 men and women recruited in 2000–2002 at 104 Dutch general practices (GPs) throughout the Netherlands.11 A mean with 95% confidence intervals is given.
women with six or more warts compared to fewer warts experienced more problems on sexual activity. In addition, women with a first episode had lower mean scores on the sexual activity dimension than women with a recurrent episode, although this difference was borderline significant (p ¼ 0.09). We also analysed the correlation between number of warts and emotional and sexual scores and found it to be significant in women; higher numbers of warts corresponding with lower CECA-6 scores (Pearson correlation coefficient: –0.33, p ¼ 0.03) as well as lower CECA-4 scores (Pearson correlation coefficient: –0.42, p ¼ 0.01). None of the above-mentioned effects were seen among men.
Discussion Overall, genital warts had a larger impact on the wellbeing of women than of men. In both genders, genital warts had the biggest impact on the emotional dimension. Among men, this impact on emotion was less in MSM compared to heterosexual men. In addition, genital warts negatively influenced sexual activity. Among heterosexual men, sexual characteristics and clinical symptoms did not influence the impact of genital warts on the emotional and sexual activity dimensions. However, among women, younger age, not having a
partner, and an increasing number of warts were significantly associated with lower scores on the sexual activity dimension. That genital warts mainly had an emotional impact was also observed in previous studies.2–5 These studies also reported gender differences, which was in line with our findings.2,4,5 The results of our study showed that the differences in reported problems between persons with genital warts compared to persons without genital warts were larger among women than among men. Women with genital warts reported significantly more anxiety and depression than female controls without genital warts. Therefore, we believe this emotional impact was most likely a true effect of having genital warts and not just the result of reporting bias. With reporting bias, we refer to the different perception of health status that exists between genders: women in general rate their health status lower than men.12,13 The additional value of our study was the inclusion of sexual characteristics and clinical symptoms, allowing us to delve deeper into possible underlying factors causing the differences in well-being between genders. The results of the genital warts-specific CECA-10 showed that the gender differences became more pronounced with increasing severity of the clinical symptoms, for example, an increase in number and/or size of genital warts resulted in a steeper decline in well-being
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Table 2. Mean CECA scores (and 95% confidence intervals) per emotional dimension (CECA-6) and sexual activity dimension (CECA-4), by gender.
Totala
CECA-6 Emotional dimension scores
CECA-4 Sexual dimension scores
women, N ¼ 49
men, N ¼ 37
women, N ¼ 44
men, N ¼ 38
n
mean (95% CI)
n
mean (95% CI)
n
mean (95% CI)
n
mean (95% CI)
49
48.4 (42.3–54.4)
37
60.9 (54.4–67.5)
44
55.7 (48.3–63.0)
38
71.5 (63.5–79.6)
Age 17–19 years
12
40.3 (23.8–56.8)
0
12
43.2 (30.6–55.8)b
0
20–24 years 25–29 years
27 6
51.9 (44.1–59.6) 54.9 (37.7–72.0)
18 10
60.4 (50.9–69.9) 67.1 (51.1–83.1)
23 5
62.5 (51.8–73.2) 68.8 (54.2–83.3)
19 10
66.4 (52.0–80.9) 80.0 (68.5–91.5)
4
39.6 (11.7–67.5)
9
55.1 (41.7–68.5)
4
37.5 (1.2–73.8)
9
72.9 (59.5–86.3)
0–1 partners
22
46.4 (35.4–57.4)
16
58.6 (49.5–67.7)
21
58.0 (46.9–69.2)
16
70.3 (59.1–81.5)
2–3 partners
16
52.6 (42.3–62.9)
10
68.3 (54.1–82.5)
16
53.9 (38.8–69.0)
10
78.8 (62.9–94.6)
4 partners
11
46.2 (36.1–56.3)
11
57.6 (42.4–72.7)
7
52.7 (41.7–63.7)
12
67.2 (47.7–86.7)
23 21
46.7 (37.6–55.9) 49.0 (39.7–58.3)
15 15
61.4 (51.7–71.1) 60.0 (50.3–69.7)
18 21
41.7 (28.4–55.0)b 68.2 (60.7–75.6)
16 15
70.3 (58.1–82.6) 76.3 (65.0–87.5)
Casual partner
5
53.3 (19.9–86.7)
6
64.6 (32.0–97.2)
5
53.8 (35.9–71.6)
6
62.5 (21.9–103.1)
Steady and casual partner
0
1
45.8 (0.0–0.0)
0
1
75.0 (0.0–0.0)
30 years Number of partners last 6 months
Current steady or casual partner No partner Steady partner
Number of lesionsc 1–2 warts
8
49.5 (39.7–59.2)
12
58.3 (47.0–69.6)
8
66.4 (47.1–85.7)b
12
71.4 (58.4–84.3)
3–5 warts
21
52.0 (42.1–61.9)
14
63.4 (50.5–76.3)
20
61.3 (50.4–72.1)
15
72.1 (59.5–84.7)
6 warts
18
45.8 (35.0–56.7)
11
60.6 (47.8–73.5)
14
44.6 (33.8–55.5)
11
71.0 (49.5–92.5)
41
50.3 (43.8–56.8)
28
58.3 (50.6–66.0)
36
58.5 (50.8–66.2)
29
72.0 (62.7–81.3)
8
38.5 (19.7–57.4)
9
69.0 (55.7–82.3)
8
43.0 (19.5–66.4)
9
70.1 (50.4–89.9)
62.9 (55.9–70.0)
28
57.1 (47.7–66.6)
30
74.8 (67.0–82.6)
4
65.6 (39.3–91.9)
0
Size of biggest lesion < 0.5 cm 0.5 cm Localization of lesions Penis/ vulva
32
47.3 (39.8–54.7)
29
Perianal region
4
58.3 (15.4–101.3)
0
Scrotum/perineal area
3
36.1 (–23.6–95.9)
1
87.5 (0.0–0.0)
3
37.5 (–44.7–119.7)
1
93.8 (0.0–0.0)
Inguinal area
2
47.9 (21.4–74.4)
3
66.7 (56.3–77.0)
2
59.4 (–59.7–178.5)
3
75.0 (43.9–106.1)
8
52.6 (33.9–71.3)
4
35.4 (13.4–57.4)
7
50.9 (26.5–75.3)
4
39.1 (–18.6–96.7)
45
48.0 (41.5–54.4)
31
61.6 (54.3–68.8)
40
53.8 (46.0–61.5)e
31
70.4 (61.4–79.3)
4
53.1 (24.8–81.4)
6
57.6 (36.3–79.0)
4
75.0 (58.8–91.2)
7
76.8 (53.3–100.3)
Multiple locationsd First or recurrent episode First episode Recurrent episode
Scoring ranges between 0 (worst HRQoL) and 100 (the best HRQoL). a T-test p < 0.05 for both dimensions. b ANOVA p < 0.05. c Of two women, the number of warts was missing. d The warts were located at the vulva/penis as well as at one or two of the other three locations (perianal region, scrotum/ perineal area, inguinal area). e ANOVA p < 0.10.
among women compared to that of men. These outcomes indicate that women indeed experienced more discomfort from genital warts than men did. A limitation of our study design was that persons were recruited from an STI clinic. Visiting the STI clinic and being uncertain about the presence of other STIs besides genital warts may have had a negative impact on HRQoL. Although we cannot rule out the possibility that women experienced more emotional distress when visiting the STI clinic in comparison to men,
we do not expect that recruitment of participants within an STI clinic would have contributed to the differences seen in HRQoL between genders. One should take into account the emotional impact of genital warts among men and women and the differences between genders when doing cost-effectiveness studies about the implementation of vaccination for girls and/or boys. Currently, two vaccines are available and approved by the Food and Drug Administration for girls: CervarixÕ and GardasilÕ . Both vaccines give
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protection against two carcinogenic types, HPV types 16 and 18.14 GardasilÕ also targets the two genital wart-related types, HPV types 6 and 11, and is also approved for boys.15 The other vaccine, CervarixÕ , has now been shown to also provide partial (cross)protection against low-risk HPV types and genital warts.16,17 HPV vaccination is already recommended in most countries for girls to prevent infections with oncogenic HPV types causing cervical cancer. Nowadays several countries are debating whether or not they should implement vaccination against HPV for boys to prevent penile and anal cancer. An important group to consider including in the target population for HPV vaccination is (HIV-infected) MSM, since anal cancer is increasingly diagnosed among this subgroup.18,19 By preventing oncogenic HPV infection, by vaccinating girls and boys, cancer incidence rates will decline. As HPV vaccination can also protect against the HPV types related to genital warts, genital warts could disappear almost completely when vaccinating both genders.20 The additional HRQoL and medical cost that will be saved when genital warts incidence would decline should be taken into account in the decision-making around HPV vaccination. In summary, we measured the impact of genital warts on HRQoL, and assessed sexual characteristics as well as clinical symptoms influencing emotional and sexual well-being of both men and women. Our results show that women experienced more discomfort from genital warts than men did. Preventing genital warts through vaccination, especially among (young) women, would therefore result in HRQoL gain. For cost-effectiveness studies assessing extending HPV vaccination to boys and/or MSM, it would be relevant to keep in mind the differences in the impact of genital warts on well-being between gender and sexual preference.
Acknowledgement The authors thank the following for their valuable contributions to the design or execution of the study: Wietske Botterhuis, Public Health Service (PHS) Den Haag, PHS North and East Gelderland, PHS Gelderland-Midden, PHS Groningen, PHS Hart voor Brabant, PHS Nijmegen, PHS Rotterdam-Rijnmond, PHS West-Brabant, University Medical Center Utrecht. All STI clinics within the municipal health centers and the hospitals, including all nurses and physicians, are especially thanked for their permission to collect data from their patients and for their effort.
Conflict of interest The authors declare that there is no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Soetens LC, Koedijk FDH, van den Broek IVF, et al. Sexually transmitted infections, including HIV, in the Netherlands in 2012 Bithoven. The Netherlands: National Institute for Public Health and the Environment, 2013; Report number: 150002003/2013. 2. Drolet M, Brisson M, Maunsell E, et al. The impact of anogenital warts on health-related quality of life: a 6-month prospective study. Sex Transm Dis 2011; 38: 949–956. 3. Badia X, Colombo JA, Lara N, et al. Combination of qualitative and quantitative methods for developing a new health related quality of life measure for patients with anogenital warts. Health Qual Life Outcomes 2005; 3: 24. 4. Woodhall S, Ramsey T, Cai C, et al. Estimation of the impact of genital warts on health-related quality of life. Sex Transm Infect 2008; 84: 161–166. 5. Woodhall SC, Jit M, Soldan K, et al. The impact of genital warts: loss of quality of life and cost of treatment in eight sexual health clinics in the UK. Sex Transm Infect 2011; 87: 458–463. 6. Testa MA and Simonson DC. Assessment of quality-oflife outcomes. N Engl J Med 1996; 334: 835–840. 7. Maggino T, Casadei D, Panontin E, et al. Impact of an HPV diagnosis on the quality of life in young women. Gynecol Oncol 2007; 107: S175–S179. 8. Drolet M, Brisson M, Maunsell E, et al. The psychosocial impact of an abnormal cervical smear result. Psychooncol 2012; 21: 1071–1081. 9. Brooks R. EuroQol: the current state of play. Health Policy 1996; 37: 53–72. 10. Vilata JJ, Varela JA, Olmos L, et al. Validation and clinical use of the CECA, a disease-specific quality of life questionnaire for patients with anogenital condylomata acuminata. Acta Derm Venereol 2008; 88: 257–262. 11. Hoeymans N, van Lindert H and Westert GP. The health status of the Dutch population as assessed by the EQ-6D. Qual Life Res 2005; 14: 655–663. 12. Konig HH, Bernert S, Angermeyer MC, et al. Comparison of population health status in six European countries: results of a representative survey using the EQ-5D questionnaire. Med Care 2009; 47: 255–261. 13. Organisation for Economic Cooperation and Development (OECD). Gender gaps in self-rated health status and self-reported limitations indailyactivities. In How’s life? OECD Publishing, 2013. DOI: 10.1787/how_life-2013-graph61-en. 14. Schiller JT, Castellsague X and Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine 2012; 30: F123–F138. 15. Centers for Disease Control and Prevention. Recommendations on the use of quadrivalent human papillomavirus vaccine in males–Advisory Committee
Downloaded from std.sagepub.com at UQ Library on June 17, 2015
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on Immunization Practices (ACIP), 2011. MMWR 2011; 60: 1705–1708. 16. Howell-Jones R, Soldan K, Wetten S, et al. Declining genital Warts in young women in England associated with HPV 16/18 vaccination: an ecological study. J Infect Dis 2013; 208: 1397–1403. 17. Szarewski A, Skinner SR, Garland SM, et al. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against low-risk HPV types (PATRICIA randomized trial): an unexpected observation. J Infect Dis 2013; 208: 1391–1396.
18. Stanley MA, Winder DM, Sterling JC, et al. HPV infection, anal intra-epithelial neoplasia (AIN) and anal cancer: current issues. BMC Cancer 2012; 12: 398. 19. van der Zee RP, Richel O, de Vries HJ, et al. The increasing incidence of anal cancer: can it be explained by trends in risk groups? Neth J Med 2013; 71: 401–411. 20. Korostil IA, Ali H, Guy RJ, et al. Near elimination of genital warts in Australia predicted with extension of human papillomavirus vaccination to males. Sex Transm Dis 2013; 40: 833–835.
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Impact of genital warts on emotional and sexual well-being differs by gender
International Journal of STD & AIDS 2014, Vol. 25(13) 949–955 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462414526706 std.sagepub.com
Henrike J Vriend1,2, Pythia T Nieuwkerk3 and Marianne AB van der Sande1,4
Abstract To assess gender-specific impact of genital warts on health-related quality of life (HRQoL), and to explore to what extent sexual characteristics and clinical symptoms influenced the impact on emotional and sexual well-being of both sexes. We conducted a survey of sexual and clinical characteristics from persons diagnosed with genital warts at STI clinics. HRQoL was measured using two measurement tools: 1) the generic EQ-5D; and 2) the genital warts-specific CECA-10 including an emotional well-being and a sexual activity dimension. The EQ-5D scores were compared with scores of the general population. Descriptive analyses were used to explore characteristics associated with HRQoL scores stratified for gender. The HRQoL-measurement tools showed that genital warts have especially an emotional impact. The impact of genital warts on HRQoL was greater for women than for men. In addition, the CECA-10 showed that in women the impact of genital warts on sexual activity was influenced by age, relationship status and number of warts. No related factors were seen in men. Genital warts have a greater impact on women than on men. In women, sexual and clinical factors influenced the impact of genital warts on well-being, whereas in men no such factors were found.
Keywords Sexually transmitted infection, genital warts, condylomata acuminata, human papillomavirus, HPV, impact, psychosexual, quality of life Date received: 26 September 2013; accepted: 11 February 2014
Introduction Genital warts are common among sexually active persons and are caused by the human papillomavirus (HPV), a virus which is sexually transmitted. In the Netherlands, the number of episodes of genital warts diagnosed at general practices doubled in a 10-year period, from 74 per 100,000 population in 2002 to 144 per 100,000 population in 2011.1 Although symptoms are in general mild, decreased emotional wellbeing has been reported among persons with genital warts compared to persons without genital warts.2–5 The well-being of a person can be expressed in terms of health-related quality of life (HRQoL). HRQoL is generally defined as a subjective and multidimensional construct encompassing a persons’ physical, emotional and social functioning, which can be affected by a medical condition and/or its subsequent therapy.6 Receiving an HPV diagnosis was previously shown to have a negative impact on HRQoL, which was the result of emotional distress caused by anxiety and fear.7 A persistent
HPV infection can result in (pre)malignant lesions or cause anogenital warts. Having these clinical outcomes could significantly reduce the HRQoL of HPV-infected persons. The overall impact of these outcomes will depend on the severity of symptoms. For example, when a woman is informed by her physician of having an abnormal smear result representing a high-grade 1 Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands 2 Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Netherlands 3 Department of Medical Psychology, Academic Medical Center, Amsterdam, the Netherlands 4 Julius Center, University Medical Center, Utrecht, the Netherlands
Corresponding author: Henrike J Vriend, National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, P.O. Box 1, 3720 BA Bilthoven, the Netherlands. Email: [email protected]
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squamous intraepithelial lesion (HSIL), this will have a more negative impact on HRQoL than being informed of having an abnormal smear representing a low-grade squamous intraepithelial lesion (LSIL).8 Similarly, having large genital warts versus small genital warts could impact HRQoL differently. In addition to the differences in clinical symptoms of genital warts, it is important to keep in mind differences in persons’ characteristics since the impact of having genital warts on a persons’ HRQoL seemed to differ between genders, women reporting lower HRQoL scores than men.2,4,5 Whether women experience more discomfort from genital warts or that these differences between genders are caused by differences in sexual characteristics or clinical symptoms of genital warts is unknown. Insight in the impact of the different clinical manifestations caused by HPV on HRQoL is important for decision-making about which vaccine to use to prevent HPV infection: the vaccine protecting against cervical cancer (CervarixÕ ) or the vaccine protecting against cervical cancer as well as genital warts (GardasilÕ ). As HRQoL is necessary for cost-effectiveness studies, it is important to delve deeper in determinants of among others the differences in HRQoL between male and female genital warts patients. This information about differences in gender is especially important since current cost-effectiveness studies are not limited to assess the impact of vaccinating women only but are also focusing on exploring the impact of vaccinating boys as well. If the HRQoL of male genital warts patients is less affected by genital warts than the HRQoL of female patients, this can have important influences on the cost-effectiveness of implementing HPV vaccination for men. Therefore, we here explored if there are certain factors that have a significantly different impact on the HRQoL of female genital warts patients than on the HRQoL of male genital warts patients, and if any such gender difference in HRQoL can be explained by a difference in sexual characteristics and/or clinical symptoms of genital warts.
Methods Between February and August 2012, attendees of 9 STI clinics across the Netherlands were asked, at the moment a first or recurrent episode of genital warts was detected, to participate in the study. Characteristics of the wart(s) (i.e. number of genital warts, size of the biggest wart, anatomical location, first or recurrent episode) were documented by a physician. At the end of the visit a questionnaire was filled out by the participant, covering sexual behaviour, history of genital warts and HRQoL.
HRQoL measurement The impact of genital warts on HRQoL was measured using a generic and a condition-specific measurement tool. The EQ-5D, which stands for European Quality of Life, is a generic HRQoL instrument that has previously been used in a wide range of clinical areas (http:// www.euroqol.org).9 The EQ-5D consists of a descriptive part in which the patient indicated the level of problems (three levels: no problems, some problems, severe problems) on five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D also includes a visual analogue scale (EQ-VAS) which was used to rate their overall state of health on the day of questionnaire administration (0 is the worst and 100 the best imaginable health state). In addition, we used the genital wart-specific CECA-10 (CECA is a Spanish acronym of Specific Questionnaire for Condylomata Acuminata). This questionnaire was previously shown to be a valid measure of HRQoL among persons with genital warts.10 The CECA-10 consists of 10 statements regarding the impact of genital warts on an emotional dimension (6 statements, CECA-6) and a sexual activity dimension (4 statements, CECA-4) (Table 1).3 Participants indicated on a five-point scale how often they experienced the specific statement (always to never). To facilitate interpretation and comprehension of the CECA scores all dimensions were standardised for a scoring between 0 (worst HRQoL) and 100 (best HRQoL). Table 1. Description of the CECA questionnaire. Item Emotional dimension 1. I am afraid that the lesions won’t disappear 2. I am anxious to know whether I am going to recover from the infection for good 3. I worry about whether the warts will get worse or if there will be some complications 4. My state of mind is upset (anxiety, depression, sadness, uneasiness. . .) 5. I feel more insecure 6. Knowing that I have the illness affects me in my daily life Sexual dimension 7. My sexual drive has decreased 8. I feel worried during the act 9. I avoid sexual relations 10. My sexual relations have decreased in quality and/or frequency CECA: Spanish acronym of Specific Questionnaire for Condylomata Acuminata. Each question allows an answer on a five-option Likert scale: ‘‘always’’ ¼ 1, ‘‘almost always’’ ¼ 2, ‘‘sometimes’’ ¼ 3, ‘‘rarely’’ ¼ 4, ‘‘never’’ ¼ 5 (items 1 and 3 also allowed the option of ‘‘not applicable’’ scored as ‘‘never’’ ¼ 5).
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Descriptive analyses To evaluate the impact of genital warts on HRQoL, we first compared EQ-5D scores per dimension to EQ-5D scores of 9685 men and women recruited in 2000–2002 at 104 general practices (GPs) across the Netherlands.11 The selection of GPs was based on region, level of urbanisation and practice type (solo or group). Within a GP, 5% of the patients registered were randomly selected, of which on average 64.5% responded. Cases and controls were matched on gender and age group. We did not have information about sexual preference in the GP control dataset, therefore we used men in general for both heterosexual men and MSM in our study population. Additionally, mean CECA scores and 95% confidence intervals (CIs) were given for women, heterosexual men, and MSM separately and tested for significance (p < 0.05) using one-way analysis of variance (ANOVA). Mean emotional and sexual CECA scores were also tested for significant differences between the categories of the independent variables (i.e. sexual characteristics and clinical symptoms) using ANOVA. Correlation coefficients and p values were estimated for continuous variables (i.e. age and number of warts). Due to small numbers of MSM, we did not show mean CECA scores per variable for this subgroup. The population included six male clients of sex workers. Since they have different sexual behaviour in comparison to other men, they are to be expected to score differently on the HRQoL measurement tools. Unfortunately, the group was too small for proper analyses and therefore this group was excluded.
Results Characteristics study population A questionnaire on sexual behaviour, genital warts history, and HRQoL, as well as a questionnaire with clinical symptoms, were available for 104 persons diagnosed with genital warts: 50 women, 38 heterosexual men, and 16 MSM. The median age of women was 22 years (interquartile range [IQR]: 20–24 years), of men 24 years (IQR: 23–29 years), and of MSM 27 years (IQR: 22–45 years). The ages ranged from 17 to 51 years among women, 22 to 53 among heterosexual men, and 20 to 71 among MSM. The median number of sexual partners in the last 6 months was similar between women and heterosexual men, although the IQR for heterosexual men was 1–4 partners and for women 1– 3. MSM reported more sexual partners in the past 6 months, median number of 3 (IQR: 2–6). Clinical symptoms showed that on average women were diagnosed with more warts than the men were (median 4.5
versus 3 warts, respectively). However, men were more often diagnosed with warts larger than 0.5 centimetre (24% of heterosexual men and 19% of MSM versus 16% of women). In addition, MSM most often had a recurrent episode, followed by heterosexual men and women (31%, 18%, and 8%, respectively).
EQ-5D scores The EQ-5D was completed by 49 women, 37 heterosexual men, and 16 MSM. For all dimensions, with exception of self-care, women reported more problems than men did (Figure 1). Men with genital warts reported fewer problems on the EQ-5D than controls except for the dimension of anxiety and depression. Among women with genital warts smaller differences with controls were noted for mobility and pain/discomfort than observed among men, but larger differences were seen for anxiety/depression. Of the participants completing the EQ-5D, 45 women, 34 heterosexual men, and 14 MSM also filled in the EQ-VAS. On the EQ-VAS women rated their current health state lower than men: 75.3 (95% CI: 70.3–80.2) for women compared to 83.7 (95% CI: 79.3–88.2) for heterosexual men and 82.1 (95%CI: 75.4–88.9) for MSM.
CECA-10 scores The emotional dimension (CECA-6) of the genital warts-specific HRQoL tool was completed by 49 women, 37 heterosexual men, and 16 MSM. The sexual activity dimension (CECA-4) was completed by 44 women, 38 heterosexual men, and 15 MSM. A mean score for the CECA-6 and CECA-4 of 60.9 (95% CI: 54.4–67.5) and 71.5 (95% CI: 63.5–79.6), respectively, was observed in heterosexual men and of 48.4 (95% CI: 42.3–54.4) and 55.7 (95% CI: 48.3–63.0), respectively, in women. These differences between women and heterosexual men were significant. MSM had higher emotional scores than heterosexual men (70.1 [95% CI: 57.4–82.7]), but scored similar on the sexual activity dimension (70.8 [95% CI: 54.5–87.2]). MSM did not significantly differ from heterosexual men. In addition, we calculated the mean CECA scores with the 95% CIs per patient characteristic stratified by women and heterosexual men (Table 2). For this analysis, we excluded MSM since numbers were too small for meaningful analysis. None of the variables within the CECA-6 contained mean scores that differed significantly from each other. However, within the CECA-4 significant differences in mean scores were found in women. Women at young age (15–19 years) compared to older age (20–29 years), women with no partner compared to women with a steady partner, and
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40 35 30 25 20 15 10
Mobility
Self-care
Usual activities
case
Pain/ discomfort
MSM
men
women
MSM
men
women
MSM
men
women
MSM
men
women
MSM
0
men
5 women
% reporting some or severe problems
952
Anxiety/ depression
control
Figure 1. Per cent of persons with genital warts ( ¼ cases) in comparison to controls representing the general Dutch population* reporting some or severe problems per dimension of the EQ-5D and 95% confidence interval (CI), by women (n ¼ 49), heterosexual men (n ¼ 37), and MSM (n ¼ 16). * Controls are based on 9685 men and women recruited in 2000–2002 at 104 Dutch general practices (GPs) throughout the Netherlands.11 A mean with 95% confidence intervals is given.
women with six or more warts compared to fewer warts experienced more problems on sexual activity. In addition, women with a first episode had lower mean scores on the sexual activity dimension than women with a recurrent episode, although this difference was borderline significant (p ¼ 0.09). We also analysed the correlation between number of warts and emotional and sexual scores and found it to be significant in women; higher numbers of warts corresponding with lower CECA-6 scores (Pearson correlation coefficient: –0.33, p ¼ 0.03) as well as lower CECA-4 scores (Pearson correlation coefficient: –0.42, p ¼ 0.01). None of the above-mentioned effects were seen among men.
Discussion Overall, genital warts had a larger impact on the wellbeing of women than of men. In both genders, genital warts had the biggest impact on the emotional dimension. Among men, this impact on emotion was less in MSM compared to heterosexual men. In addition, genital warts negatively influenced sexual activity. Among heterosexual men, sexual characteristics and clinical symptoms did not influence the impact of genital warts on the emotional and sexual activity dimensions. However, among women, younger age, not having a
partner, and an increasing number of warts were significantly associated with lower scores on the sexual activity dimension. That genital warts mainly had an emotional impact was also observed in previous studies.2–5 These studies also reported gender differences, which was in line with our findings.2,4,5 The results of our study showed that the differences in reported problems between persons with genital warts compared to persons without genital warts were larger among women than among men. Women with genital warts reported significantly more anxiety and depression than female controls without genital warts. Therefore, we believe this emotional impact was most likely a true effect of having genital warts and not just the result of reporting bias. With reporting bias, we refer to the different perception of health status that exists between genders: women in general rate their health status lower than men.12,13 The additional value of our study was the inclusion of sexual characteristics and clinical symptoms, allowing us to delve deeper into possible underlying factors causing the differences in well-being between genders. The results of the genital warts-specific CECA-10 showed that the gender differences became more pronounced with increasing severity of the clinical symptoms, for example, an increase in number and/or size of genital warts resulted in a steeper decline in well-being
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Table 2. Mean CECA scores (and 95% confidence intervals) per emotional dimension (CECA-6) and sexual activity dimension (CECA-4), by gender.
Totala
CECA-6 Emotional dimension scores
CECA-4 Sexual dimension scores
women, N ¼ 49
men, N ¼ 37
women, N ¼ 44
men, N ¼ 38
n
mean (95% CI)
n
mean (95% CI)
n
mean (95% CI)
n
mean (95% CI)
49
48.4 (42.3–54.4)
37
60.9 (54.4–67.5)
44
55.7 (48.3–63.0)
38
71.5 (63.5–79.6)
Age 17–19 years
12
40.3 (23.8–56.8)
0
12
43.2 (30.6–55.8)b
0
20–24 years 25–29 years
27 6
51.9 (44.1–59.6) 54.9 (37.7–72.0)
18 10
60.4 (50.9–69.9) 67.1 (51.1–83.1)
23 5
62.5 (51.8–73.2) 68.8 (54.2–83.3)
19 10
66.4 (52.0–80.9) 80.0 (68.5–91.5)
4
39.6 (11.7–67.5)
9
55.1 (41.7–68.5)
4
37.5 (1.2–73.8)
9
72.9 (59.5–86.3)
0–1 partners
22
46.4 (35.4–57.4)
16
58.6 (49.5–67.7)
21
58.0 (46.9–69.2)
16
70.3 (59.1–81.5)
2–3 partners
16
52.6 (42.3–62.9)
10
68.3 (54.1–82.5)
16
53.9 (38.8–69.0)
10
78.8 (62.9–94.6)
4 partners
11
46.2 (36.1–56.3)
11
57.6 (42.4–72.7)
7
52.7 (41.7–63.7)
12
67.2 (47.7–86.7)
23 21
46.7 (37.6–55.9) 49.0 (39.7–58.3)
15 15
61.4 (51.7–71.1) 60.0 (50.3–69.7)
18 21
41.7 (28.4–55.0)b 68.2 (60.7–75.6)
16 15
70.3 (58.1–82.6) 76.3 (65.0–87.5)
Casual partner
5
53.3 (19.9–86.7)
6
64.6 (32.0–97.2)
5
53.8 (35.9–71.6)
6
62.5 (21.9–103.1)
Steady and casual partner
0
1
45.8 (0.0–0.0)
0
1
75.0 (0.0–0.0)
30 years Number of partners last 6 months
Current steady or casual partner No partner Steady partner
Number of lesionsc 1–2 warts
8
49.5 (39.7–59.2)
12
58.3 (47.0–69.6)
8
66.4 (47.1–85.7)b
12
71.4 (58.4–84.3)
3–5 warts
21
52.0 (42.1–61.9)
14
63.4 (50.5–76.3)
20
61.3 (50.4–72.1)
15
72.1 (59.5–84.7)
6 warts
18
45.8 (35.0–56.7)
11
60.6 (47.8–73.5)
14
44.6 (33.8–55.5)
11
71.0 (49.5–92.5)
41
50.3 (43.8–56.8)
28
58.3 (50.6–66.0)
36
58.5 (50.8–66.2)
29
72.0 (62.7–81.3)
8
38.5 (19.7–57.4)
9
69.0 (55.7–82.3)
8
43.0 (19.5–66.4)
9
70.1 (50.4–89.9)
62.9 (55.9–70.0)
28
57.1 (47.7–66.6)
30
74.8 (67.0–82.6)
4
65.6 (39.3–91.9)
0
Size of biggest lesion < 0.5 cm 0.5 cm Localization of lesions Penis/ vulva
32
47.3 (39.8–54.7)
29
Perianal region
4
58.3 (15.4–101.3)
0
Scrotum/perineal area
3
36.1 (–23.6–95.9)
1
87.5 (0.0–0.0)
3
37.5 (–44.7–119.7)
1
93.8 (0.0–0.0)
Inguinal area
2
47.9 (21.4–74.4)
3
66.7 (56.3–77.0)
2
59.4 (–59.7–178.5)
3
75.0 (43.9–106.1)
8
52.6 (33.9–71.3)
4
35.4 (13.4–57.4)
7
50.9 (26.5–75.3)
4
39.1 (–18.6–96.7)
45
48.0 (41.5–54.4)
31
61.6 (54.3–68.8)
40
53.8 (46.0–61.5)e
31
70.4 (61.4–79.3)
4
53.1 (24.8–81.4)
6
57.6 (36.3–79.0)
4
75.0 (58.8–91.2)
7
76.8 (53.3–100.3)
Multiple locationsd First or recurrent episode First episode Recurrent episode
Scoring ranges between 0 (worst HRQoL) and 100 (the best HRQoL). a T-test p < 0.05 for both dimensions. b ANOVA p < 0.05. c Of two women, the number of warts was missing. d The warts were located at the vulva/penis as well as at one or two of the other three locations (perianal region, scrotum/ perineal area, inguinal area). e ANOVA p < 0.10.
among women compared to that of men. These outcomes indicate that women indeed experienced more discomfort from genital warts than men did. A limitation of our study design was that persons were recruited from an STI clinic. Visiting the STI clinic and being uncertain about the presence of other STIs besides genital warts may have had a negative impact on HRQoL. Although we cannot rule out the possibility that women experienced more emotional distress when visiting the STI clinic in comparison to men,
we do not expect that recruitment of participants within an STI clinic would have contributed to the differences seen in HRQoL between genders. One should take into account the emotional impact of genital warts among men and women and the differences between genders when doing cost-effectiveness studies about the implementation of vaccination for girls and/or boys. Currently, two vaccines are available and approved by the Food and Drug Administration for girls: CervarixÕ and GardasilÕ . Both vaccines give
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protection against two carcinogenic types, HPV types 16 and 18.14 GardasilÕ also targets the two genital wart-related types, HPV types 6 and 11, and is also approved for boys.15 The other vaccine, CervarixÕ , has now been shown to also provide partial (cross)protection against low-risk HPV types and genital warts.16,17 HPV vaccination is already recommended in most countries for girls to prevent infections with oncogenic HPV types causing cervical cancer. Nowadays several countries are debating whether or not they should implement vaccination against HPV for boys to prevent penile and anal cancer. An important group to consider including in the target population for HPV vaccination is (HIV-infected) MSM, since anal cancer is increasingly diagnosed among this subgroup.18,19 By preventing oncogenic HPV infection, by vaccinating girls and boys, cancer incidence rates will decline. As HPV vaccination can also protect against the HPV types related to genital warts, genital warts could disappear almost completely when vaccinating both genders.20 The additional HRQoL and medical cost that will be saved when genital warts incidence would decline should be taken into account in the decision-making around HPV vaccination. In summary, we measured the impact of genital warts on HRQoL, and assessed sexual characteristics as well as clinical symptoms influencing emotional and sexual well-being of both men and women. Our results show that women experienced more discomfort from genital warts than men did. Preventing genital warts through vaccination, especially among (young) women, would therefore result in HRQoL gain. For cost-effectiveness studies assessing extending HPV vaccination to boys and/or MSM, it would be relevant to keep in mind the differences in the impact of genital warts on well-being between gender and sexual preference.
Acknowledgement The authors thank the following for their valuable contributions to the design or execution of the study: Wietske Botterhuis, Public Health Service (PHS) Den Haag, PHS North and East Gelderland, PHS Gelderland-Midden, PHS Groningen, PHS Hart voor Brabant, PHS Nijmegen, PHS Rotterdam-Rijnmond, PHS West-Brabant, University Medical Center Utrecht. All STI clinics within the municipal health centers and the hospitals, including all nurses and physicians, are especially thanked for their permission to collect data from their patients and for their effort.
Conflict of interest The authors declare that there is no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Soetens LC, Koedijk FDH, van den Broek IVF, et al. Sexually transmitted infections, including HIV, in the Netherlands in 2012 Bithoven. The Netherlands: National Institute for Public Health and the Environment, 2013; Report number: 150002003/2013. 2. Drolet M, Brisson M, Maunsell E, et al. The impact of anogenital warts on health-related quality of life: a 6-month prospective study. Sex Transm Dis 2011; 38: 949–956. 3. Badia X, Colombo JA, Lara N, et al. Combination of qualitative and quantitative methods for developing a new health related quality of life measure for patients with anogenital warts. Health Qual Life Outcomes 2005; 3: 24. 4. Woodhall S, Ramsey T, Cai C, et al. Estimation of the impact of genital warts on health-related quality of life. Sex Transm Infect 2008; 84: 161–166. 5. Woodhall SC, Jit M, Soldan K, et al. The impact of genital warts: loss of quality of life and cost of treatment in eight sexual health clinics in the UK. Sex Transm Infect 2011; 87: 458–463. 6. Testa MA and Simonson DC. Assessment of quality-oflife outcomes. N Engl J Med 1996; 334: 835–840. 7. Maggino T, Casadei D, Panontin E, et al. Impact of an HPV diagnosis on the quality of life in young women. Gynecol Oncol 2007; 107: S175–S179. 8. Drolet M, Brisson M, Maunsell E, et al. The psychosocial impact of an abnormal cervical smear result. Psychooncol 2012; 21: 1071–1081. 9. Brooks R. EuroQol: the current state of play. Health Policy 1996; 37: 53–72. 10. Vilata JJ, Varela JA, Olmos L, et al. Validation and clinical use of the CECA, a disease-specific quality of life questionnaire for patients with anogenital condylomata acuminata. Acta Derm Venereol 2008; 88: 257–262. 11. Hoeymans N, van Lindert H and Westert GP. The health status of the Dutch population as assessed by the EQ-6D. Qual Life Res 2005; 14: 655–663. 12. Konig HH, Bernert S, Angermeyer MC, et al. Comparison of population health status in six European countries: results of a representative survey using the EQ-5D questionnaire. Med Care 2009; 47: 255–261. 13. Organisation for Economic Cooperation and Development (OECD). Gender gaps in self-rated health status and self-reported limitations indailyactivities. In How’s life? OECD Publishing, 2013. DOI: 10.1787/how_life-2013-graph61-en. 14. Schiller JT, Castellsague X and Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine 2012; 30: F123–F138. 15. Centers for Disease Control and Prevention. Recommendations on the use of quadrivalent human papillomavirus vaccine in males–Advisory Committee
Downloaded from std.sagepub.com at UQ Library on June 17, 2015
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on Immunization Practices (ACIP), 2011. MMWR 2011; 60: 1705–1708. 16. Howell-Jones R, Soldan K, Wetten S, et al. Declining genital Warts in young women in England associated with HPV 16/18 vaccination: an ecological study. J Infect Dis 2013; 208: 1397–1403. 17. Szarewski A, Skinner SR, Garland SM, et al. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against low-risk HPV types (PATRICIA randomized trial): an unexpected observation. J Infect Dis 2013; 208: 1391–1396.
18. Stanley MA, Winder DM, Sterling JC, et al. HPV infection, anal intra-epithelial neoplasia (AIN) and anal cancer: current issues. BMC Cancer 2012; 12: 398. 19. van der Zee RP, Richel O, de Vries HJ, et al. The increasing incidence of anal cancer: can it be explained by trends in risk groups? Neth J Med 2013; 71: 401–411. 20. Korostil IA, Ali H, Guy RJ, et al. Near elimination of genital warts in Australia predicted with extension of human papillomavirus vaccination to males. Sex Transm Dis 2013; 40: 833–835.
Downloaded from std.sagepub.com at UQ Library on June 17, 2015
