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Contribution of demographic, psychological and disease-related factors to quality of life in women with high-grade vulval intraepithelial neoplasia
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Gynecologic Oncology 110 (2008) 185 – 189 www.elsevier.com/locate/ygyno
Contribution of demographic, psychological and disease-related factors to quality of life in women with high-grade vulval intraepithelial neoplasia T.S. Shylasree a,⁎, V. Karanjgaokar b , A. Tristram a , A.R. Wilkes c , A.B. MacLean b , A.N. Fiander a a
Department of Gynaecological Oncology, Cardiff and Vale NHS Trust and Wales College of Medicine, Cardiff University, UK b Royal Free and University College Medical School (Royal Free Campus), University College London, UK c Department of Anaesthetics, Wales College of Medicine, Cardiff University, UK Received 2 March 2008 Available online 3 June 2008
Abstract Objectives. To quantify the effect of demographic, psychological and disease-related factors on Quality of life (QoL) outcomes in women with high-grade vulval intraepithelial neoplasia (VIN2–3). To obtain qualitative data on the effect of disease and treatment in these women and their partners. To assess the participants' perception of their risk of developing of vulval cancer and its relation to QoL outcomes. Methods. A questionnaire was constructed using existing instruments to measure the effect of demographic, psychological and disease-related factors on QoL outcomes. Free text space was provided for qualitative data. The questionnaire was mailed to women attending two specialist VIN clinics. Results. One hundred and fifty women were invited for the study. Eighty-two responded (54.6%) of which forty-four (53.6%) were sexually active. Demographic factors (age and or living situation) had a significant effect on emotional health and body image. Psychological factors (anxiety and depression) had a significant effect on all aspects of QoL. Disease-related factors did not have a measurable effect on QoL outcomes, although the qualitative data revealed that various aspects of VIN had affected the lives of these women and their partners. There was a significant positive association between a perceived risk of developing vulval cancer with worsening general and emotional health. Conclusion. Psychological co-morbidity and various demographic factors should be considered while managing women with VIN. Accurate information regarding the development of vulval cancer should be given. The findings of this preliminary study will assist the construction of VIN-specific QoL instruments in the future. © 2008 Elsevier Inc. All rights reserved. Keywords: Vulval intraepithelial neoplasia; Quality of life outcomes
Introduction High-grade vulval intraepithelial neoplasia (VIN2–3) is a pre-invasive disease of the vulva, which predominantly affects premenopausal women and is often accompanied by severe symptoms [1]. The incidence of VIN is increasing and the age at diagnosis decreasing, [2–4]. Case series suggest that between 80–95% of women with VIN are symptomatic[5,1]. The reason why VIN is symptomatic in some women and not in others is less well understood. ⁎ Corresponding author. Department of Gynaecological Oncology, Cardiff and Vale NHS Trust, Penlan Road, Llandough Hospital, Llandough, Wales, UK. E-mail address: [email protected] (T.S. Shylasree). 0090-8258/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2008.04.023
The natural history of untreated disease is largely unknown, as most women undergo treatment, either because of symptoms or concern about malignant potential. A systematic review including 3322 patients with VIN estimated the invasive potential to be 3.3% of treated and 9% of untreated patients [1]. The mean time to progression in this review was 55 months and the mean follow up time only 33 months and it has therefore been suggested that this resulted in an underestimate of the risk of invasion [6]. Complete spontaneous regression has also been noted in a small number of untreated women [1,7]. Treatment options include surgical excision, laser ablation and conservative management with regular follow up [8]. Novel treatments for women preferring not to have surgery have been investigated and include therapeutic vaccination, photodynamic
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therapy and topical treatment with imiquimod and cidofovir, with variable results [9–16]. Health related QoL (HR-QoL) is a multidimensional, patient centred concept. It encompasses physical health and symptoms, functional status, mental well being and social functioning. Four aspects of VIN might be predicted to impact on quality of life (QoL): potential for malignant progression or recurrence: symptoms: side effects of treatment and its association with human papillomavirus (HPV), which is sexually transmitted. Four studies have looked at sexual dysfunction and quality of life following surgery in women with VIN [17–20] {Literature search conducted using electronic databases: Medline (1966 to present), CINAHL (1982 to present), Cochrane DSR, database of abstracts of reviews of effectiveness (DARE), CCTR, CMR, HTA and NHSEED using key words: vulval intraepithelial neoplasia, quality of life, sexual dysfunction, outcomes following surgery for VIN}. There are currently no disease-specific QoL measurement tools for VIN. The goals of this study were to • Quantify the effect of demographic, psychological and diseaserelated factors in women with high-grade VIN on general and emotional health, body image and sexual health as measured by existing instruments. • Obtain qualitative data exploring the effect of disease and treatment on these women and the reasons for sexual inactivity or discontent and the effect of disease on partners. • Assess the participants' perception of their risk of developing of vulval cancer and its relation to QoL outcomes. Methods Approval for the study was obtained from the South East Wales Research Ethics Committee and Whittington Research Ethics Committee, United Kingdom.
Participants Women who had attended one of two UK specialist VIN clinics were recruited. Questionnaires were sent to 100 patients from Cardiff and Vale NHS
Table 1 Relevant SF 12 questions on general, emotional health and body image Questions about general health (5 responses) In general, would you say your health is now? Did your symptoms/health interfere with your usual activities? Did your symptoms/health interfere with your sleep? Did your symptoms/health interfere with your social life? Did your symptoms/health interfere with your holidays and outings? Questions about your feelings and emotions (3 responses) How much have your emotions or feelings interfered with your 1) Work or other regular activities 2) Social activities 3) Holidays and outings Questions on body image (five responses) Have you been feeling self-conscious about your appearance? Have you felt less physically attractive as a result of your disease? Have you been feeling less feminine as a result of your disease? Have you been feeling less sexually attractive as a result of disease? Have you been dissatisfied with your body?
Table 2 Sexual self-rating Sabbatsburg questionnaire (5 responses) My interest in sex during last month has been In comparison to previous years my interest in sex is now My sexual activity during the last month has been In comparison to previous years my sexual activity is now My sex life during the last month has been In comparison to previous years my sex life is now Sex during the last month has given me In comparison to previous years sex now gives me My ability to reach orgasm during the last month has been In comparison to previous years my ability to reach orgasm has been Sex is for me: In comparison to previous years the importance of sex has for me
Trust, Cardiff and 50 patients from the Royal Free Hospital, London in October 2005. A reminder letter was sent two months later to non-responders.
Instruments A questionnaire was constructed to quantify the demographic, psychological and disease-related factors to be assessed and the effect of these factors on QoL outcomes (general health, emotional health, body image and sexual health). Demographic data collected included questions on age, living status and smoking history. Living status was divided into three groups: single/living alone, married/living with partner, separated/divorced/widowed. Psychological status was measured using the standard Hospital Anxiety and Depression Scale (HADS) [21]. HADS is a 14-item scale, with 7 questions assessing anxiety (HADS-A) and 7 assessing depression (HADS-D). Total scores for each part range from 0–21: a score of less than 7 is considered normal, between 8–10 indicates possible clinical levels of anxiety or depression and a score of 11 or above indicates definite clinical anxiety or depression. Disease-related questions recorded the time since first diagnosis, symptoms at initial presentation, treatment history and participation in VIN research trials. Participants were also asked to estimate their risk of developing vulval cancer on a scale of 0–100% and the results were correlated with the QoL outcomes. Four aspects of QoL were measured: general health, emotional health, body image and sexual health. Questions on general health, emotional health and body image were constructed using relevant questions from the twelve item short form health survey (SF12) [22], (Table 1). Sexual health was measured using the revised Sabbatsburg self-rating questionnaire [23] (Table 2). This questionnaire has 12 questions with scores ranging from 0–60, with 60 denoting maximum sexual activity. Free text comments were invited regarding women's perception of the effect the disease had on their partners, the reasons for sexual inactivity or discontent and the effects of treatment, with a final section for any additional comments. The questionnaire was initially piloted amongst 10 women attending VIN clinics on both sites and alterations made for clarity.
Statistics The effects of demographic, psychological and disease-related factors on the four different QoL outcomes (general health, sexual health, body image and emotional health) were calculated using the general linear model analysis technique and multiple pair wise comparisons (adjusted for Bonferroni correction) using SPSS version12 software. A p-value of 0.05 was considered to indicate the level of statistical significance.
Results Descriptive statistics Demographic factors Of the 150 women invited to participate in the study, 82 responded (54.6%). The median age was 48 years (range 26–
T.S. Shylasree et al. / Gynecologic Oncology 110 (2008) 185–189 Table 3 Results of HADS for women with VIN (n = 82)
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Box 1 Free text comments on the impact of VIN on quality of life
HADS
Anxiety
Depression
None (score 0–7) Mild (score 8–10) Moderate (score 11–14) Severe (15–21)
45% 17% 16% 16%
54% 24% 12% 6%
81) and 35 (43%) were current smokers. Forty-four (53.6%) of the respondents were sexually active. Nineteen (23%) were single or lived alone, forty-four (54%) were married or lived with a partner, and nineteen (23%) were separated or divorced or widowed. Psychological factors The mean and median scores for HADS anxiety was 8 and HADS depression 6. Thirty two percent of the study group had moderate to severe anxiety and 18% had moderate to severe depression, (Table 3). Disease-related factors VIN had been diagnosed more than 5 years, prior to the study in 35 women (42.6%). Of the 68 women (83%) who were symptomatic at the time of presentation, 58 (85%) had vulval itching and 39 (57%) vulval pain. Nine patients (11%) answered that they were managed conservatively after biopsy diagnosis, thirty four (41.4%) had one form of treatment, twenty five (30.4%) had two and seven (8.5%) had received more than two forms of treatment. Twenty five patients (30.4%) had participated in research trials involving VIN. The perceived risk of developing vulval cancer is shown in Table 4. Correlates with patient demographics Age had an effect on emotional health (p = 0.02), such that increasing age led to worsening emotional health. When living status was examined by multiple pair wise comparisons, there was a significant difference between women who were single/ living alone and those who were separated/divorced/widowed with the latter group having better body image (p = 0.014 adjusted for Bonferroni correction) and better emotional health (p = 0.025 adjusted for Bonferroni correction).
I suffer from depression, compassion and a female nurse would help. I was diagnosed in my first pregnancy and am worried that it may recur in my next pregnancy. I feel that I have a dirty disease that has affected me emotionally and physically. I find it hard that VIN is sex related and I haven't had sex for many years. Celibacy is simpler, for fear of infecting a partner. I have stopped wearing trousers, VIN has affected my confidence and I no longer feel sexually attractive. I am very fortunate that I can have regular checkups. I am worried about my daughter getting the same problems. Wearing clothes is difficult. We need help to improve sex drive and soreness.
and depression levels led to worsening general health (HADS-A p b 0.01, HADS-D p b 0.01) emotional health (HADS-A pb 0.001, HADS-D pb 0.01) and body image (HADS-A p b 0.001, HADS-D p b 0.01). For sexual health, an increase in HADS depression led to worsening sexual health (HADS-D p b 0.01) whereas HADS anxiety (HADS-A p= 0.093) did not have a significant effect. Correlates with disease-related status The presence or absence of symptoms, duration of VIN, number of treatments and participation in research trials did not have a significant effect on any of the outcomes of QoL. There was a significant positive association between a perceived risk of developing vulval cancer of 10% or greater with worsening general and emotional health (p = 0.001, p = 0.002 Spearman's rho = 0.41 respectively). Body image and sexual health were not associated with the women's perception of developing vulval cancer. Qualitative data
Correlates with psychological status The effect of both HADS scores (HADS-A and HADS-D) on the outcomes of QoL was such that an increase in the anxiety
Table 4 Estimated risk of developing vulval cancer Estimated risk of developing vulval cancer
Number of women n
%
0–10% 11–50% 51–90% 91–100% Did not give a figure
15 27 13 4 23
18 33 16 5 28
There was a broad range of comments on the impact of VIN on quality of life with examples shown in text box 1. Thirty six women gave free text comments on the effect of various treatments; of which twenty six women said that the most common side effect of surgery, laser and topical applications was pain. One woman said that she ‘had a very tiring time because of various treatments’ and another said that she was ‘very young and was traumatised by surgery’. There was a comment on a lack of sensation after surgical excision. There were three positive comments about surgical excision where the procedure had eradicated symptoms. One participant wrote a separate 2 paged letter along with the completed questionnaire saying that she had ‘suffered a great deal because of this wretched disease’ and after trying almost every
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treatment available for VIN she had come to terms with the disease. She felt that the last few years had been better as the course of the disease and its treatment was being researched by the medical fraternity. Twenty one women gave reasons for being sexually inactive and 33 women for being sexually unhappy. Common reasons for being sexually inactive, unhappy or less satisfied were soreness or pain, fear, self consciousness, older age, lack of sex drive, no current partner and fear of passing on the virus or disease. Thirty five women (56%) with current or previous partners answered the question on their partner or husband being affected by the disease. There was a wide range of comments about partners being affected. Seven women said their partners were supportive, accepting or understanding although one wrote ‘constant support, but our marriage has suffered, with many tears and feelings of failure’. The majority said that their relationship had suffered in some way. One woman said “My previous partner left, he said it was better to die”, another that “I have pushed him to the edge by crying and moaning”. Discussion This study examined the effect of demographic, psychological and disease-related factors on the QoL outcomes of women attending two specialist VIN clinics in the UK, to quantify their effect upon general, emotional and sexual health including body image as measured by existing instruments. Demographic factors were shown to affect some aspects of QoL in our study. Poorer quality of life was associated with increasing age and being single with worse emotional health and body image. Poorer sexual function and QoL has been noted in older women undergoing surgical excision of VIN in other studies [19]. Depression affected all aspects of health in the present study. Loss of libido and poor body image are important depressive symptoms and indicate that women with VIN are vulnerable to psychological morbidity. Anxiety affected general and emotional health as well as body image but did not have an effect on sexual health in this study. Studies in women with vulvodynia have shown high levels of depression and anxiety; depression being more prominent than anxiety [24,25]. Clinical variables such as duration of disease, presence of symptoms and the number of treatments did not have a measurable impact on QoL. The patient response rate in our study was 54.6% which is good for a postal based questionnaire study, although nonresponse might introduce bias either way. One limitation of the study was that the cross-sectional research design did not permit examination of a possible sequential relationship between clinical variables affecting QoL or causing psychological morbidity. Further study is required to assess how best to address longitudinal study of women with VIN. This study show, however that psychological morbidity is highly prevalent in VIN patients. The conventional management of women with VIN is by surgical excision of affected tissue. In the systematic review of 3322 VIN3 patients, 1921 women were treated surgically [1]. The difficulty arises when the disease is multifocal, multicentric and persistent, when extensive surgery is required that will alter
the cosmetic appearance and functional capacity of the vulva and in turn will have significant effects on QoL. It has been shown that up to a half of patients suffer both sexual dysfunction and psychological problems following radical and simple vulvectomy [8,26]. The magnitude of excision has been shown to be proportional to somatopsychic reactions and sexual dysfunction, [27,19]. Women also indicated their wish to receive information related to sexual functioning and felt it should also be available to their partner [8]. Novel forms of treatment such as imiquimod and cidofovir are associated with significant short term side effects, but preserve the anatomy and functional aspects of the vulva [15,28].There are no long term data on disease recurrence or progression with these forms of treatment. In the present study, all forms of treatment had adverse side effects on patients, pain being the predominant side effect. The anatomical extent of the disease and treatment failure was not evaluated in our study making comparisons between various treatments difficult. The appropriate management of VIN is still evolving and the various treatment modalities have emerged over time. The lack of larger studies comparing the effect of various treatments for VIN on QoL should be an area for future research. The reasons given for sexual inactivity and sexual unhappiness indicate a significant interaction between demographic, psychological and disease-related factors affecting individuals differently. Women who have other chronic genital disorders will often lose their interest in sexual activity leading to problems with sexual dysfunction, [29,30]. It has been suggested that it is important to give these women the opportunity to express their concerns regarding sexual functioning and to offer support with the necessary expertise to address such problems [31]. The women's perception of their partners' reaction to VIN was negative on the whole. Examining whether this was a true reflection of the situation was not part of this study, but would be important in order to address the issues raised. Studies on vulval vestibulitis have shown similar effects of disease on partners to those found in the present study [32]. The women's perception of the likelihood of developing vulval cancer increased with worsening general and emotional health. Catastrophizing is the tendency to overemphasize the probability and possible consequences of a catastrophic outcome and has been shown to be related to anxiety [33]. This needs to be addressed by giving women accurate information. There is currently no validated quality of life assessment tool for use in women with VIN. The findings of this study will assist the construction of VIN-specific QoL instruments in future, which can be used in trials comparing treatments for VIN. Summary Women with VIN experience significant psychological morbidity. Psychological factors and to some extent demographic factors were much stronger determinants of QoL in women with VIN compared to clinical factors. Multidisciplinary management of these women should therefore be considered in order to take into account the psychological co-morbidity. Accurate written information should be provided about the risk of developing invasive disease.
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Further research is needed to establish a VIN-specific instrument to measure quality of life, the benefit of multidisciplinary input and the true impact of VIN on partners. Conflict of interest statement The authors declare that they have no conflicts of interest to disclose.
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[14] Jayne CJ, Kaufman RH. Treatment of vulvar intraepithelial neoplasia 2/3 with imiquimod. J Reprod Med May 2002;47(5):395–8. [15] Todd RW, Etherington IJ, Luesley DM. The effects of 5% imiquimod cream on high-grade vulval intraepithelial neoplasia. Gynecol Oncol Apr 2002;85(1):67–70. [16] Le T, Menard C, Hicks-Boucher W, Hopkins L, Weberpals J, Fung-KeeFung M. Final results of a phase 2 study using continuous 5% Imiquimod cream application in the primary treatment of high-grade vulva intraepithelial neoplasia. Gynecol Oncol Sep 2007;106(3):579–84. [17] Andersen BL, Turnquist D, LaPolla J, Turner D. Sexual functioning after treatment of in situ vulvar cancer: preliminary report. Obstet Gynecol Jan 1988;71(1):15–9. [18] Narayansingh GV, Cumming GP, Parkin DP, McConell DT, Honey E, Kolhe PS. Flap repair: an effective strategy for minimising sexual morbidity associated with the surgical management of vulval intra epithelial neoplasia. J R Coll Surg Edinb 2000 Apr;45(2):81–4. [19] Likes WM, Stegbauer C, Tillmanns T, Pruett J. Correlates of sexual function following vulvar excision. Gynecol Oncol Jun 2007;105(3):600–3. [20] Likes WM, Stegbauer C, Tillmanns T, Pruett J. Pilot study of sexual function and quality of life after excision for vulvar intraepithelial neoplasia. J Reprod Med Jan 2007;52(1):23–7. [21] Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand Jun 1983;67(6):361–70. [22] Ware Jr J, Kosinski M, Keller SD. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care Mar 1996;34(3):220–33. [23] Garratt AM, Torgerson DJ, Wyness J, Hall MH, Reid DM. Measuring sexual functioning in premenopausal women. Br J Obstet Gynaecol Apr 1995;102(4):311–6. [24] Nylanderlundqvist E, Bergdahl J. Vulvar vestibulitis: evidence of depression and state anxiety in patients and partners. Acta Derm Venereol 2003;83(5):369–73. [25] Aikens JE, Reed BD, Gorenflo DW, Haefner HK. Depressive symptoms among women with vulvar dysesthesia. Am J Obstet Gynecol Aug 2003;189(2):462–6. [26] Andreasson B, Moth I, Jensen SB, Bock JE. Sexual function and somatopsychic reactions in vulvectomy-operated women and their partners. Acta Obstet Gynecol Scand 1986;65(1):7–10. [27] Thuesen B, Andreasson B, Bock JE. Sexual function and somatopsychic reactions after local excision of vulvar intra-epithelial neoplasia. Acta Obstet Gynecol Scand Feb 1992;71(2):126–8. [28] Tristram A, Fiander A. Clinical responses to Cidofovir applied topically to women with high grade vulval intraepithelial neoplasia. Gynecol Oncol Dec 2005;99(3):652–5. [29] Dalziel KL. Effect of lichen sclerosus on sexual function and parturition. J Reprod Med May 1995;40(5):351–4. [30] Marin MG, King R, Dennerstein GJ, Sfameni S. Dyspareunia and vulvar disease. J Reprod Med Nov 1998;43(11):952–8. [31] Neill SM, Tatnall FM, Cox NH. Guidelines for the management of lichen sclerosus. Br J Dermatol Oct 2002;147(4):640–9. [32] Bornstein J, Shapiro S, Goldshmid N, Goldik Z, Lahat N, Abramovici H. Severe vulvar vestibulitis. Relation to HPV infection. J Reprod Med Aug 1997;42(8):514–8. [33] Turner JA, Aaron LA. Pain-related catastrophizing: what is it? Clin J Pain Mar 2001;17(1):65–71.
Gynecologic Oncology 110 (2008) 185 – 189 www.elsevier.com/locate/ygyno
Contribution of demographic, psychological and disease-related factors to quality of life in women with high-grade vulval intraepithelial neoplasia T.S. Shylasree a,⁎, V. Karanjgaokar b , A. Tristram a , A.R. Wilkes c , A.B. MacLean b , A.N. Fiander a a
Department of Gynaecological Oncology, Cardiff and Vale NHS Trust and Wales College of Medicine, Cardiff University, UK b Royal Free and University College Medical School (Royal Free Campus), University College London, UK c Department of Anaesthetics, Wales College of Medicine, Cardiff University, UK Received 2 March 2008 Available online 3 June 2008
Abstract Objectives. To quantify the effect of demographic, psychological and disease-related factors on Quality of life (QoL) outcomes in women with high-grade vulval intraepithelial neoplasia (VIN2–3). To obtain qualitative data on the effect of disease and treatment in these women and their partners. To assess the participants' perception of their risk of developing of vulval cancer and its relation to QoL outcomes. Methods. A questionnaire was constructed using existing instruments to measure the effect of demographic, psychological and disease-related factors on QoL outcomes. Free text space was provided for qualitative data. The questionnaire was mailed to women attending two specialist VIN clinics. Results. One hundred and fifty women were invited for the study. Eighty-two responded (54.6%) of which forty-four (53.6%) were sexually active. Demographic factors (age and or living situation) had a significant effect on emotional health and body image. Psychological factors (anxiety and depression) had a significant effect on all aspects of QoL. Disease-related factors did not have a measurable effect on QoL outcomes, although the qualitative data revealed that various aspects of VIN had affected the lives of these women and their partners. There was a significant positive association between a perceived risk of developing vulval cancer with worsening general and emotional health. Conclusion. Psychological co-morbidity and various demographic factors should be considered while managing women with VIN. Accurate information regarding the development of vulval cancer should be given. The findings of this preliminary study will assist the construction of VIN-specific QoL instruments in the future. © 2008 Elsevier Inc. All rights reserved. Keywords: Vulval intraepithelial neoplasia; Quality of life outcomes
Introduction High-grade vulval intraepithelial neoplasia (VIN2–3) is a pre-invasive disease of the vulva, which predominantly affects premenopausal women and is often accompanied by severe symptoms [1]. The incidence of VIN is increasing and the age at diagnosis decreasing, [2–4]. Case series suggest that between 80–95% of women with VIN are symptomatic[5,1]. The reason why VIN is symptomatic in some women and not in others is less well understood. ⁎ Corresponding author. Department of Gynaecological Oncology, Cardiff and Vale NHS Trust, Penlan Road, Llandough Hospital, Llandough, Wales, UK. E-mail address: [email protected] (T.S. Shylasree). 0090-8258/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2008.04.023
The natural history of untreated disease is largely unknown, as most women undergo treatment, either because of symptoms or concern about malignant potential. A systematic review including 3322 patients with VIN estimated the invasive potential to be 3.3% of treated and 9% of untreated patients [1]. The mean time to progression in this review was 55 months and the mean follow up time only 33 months and it has therefore been suggested that this resulted in an underestimate of the risk of invasion [6]. Complete spontaneous regression has also been noted in a small number of untreated women [1,7]. Treatment options include surgical excision, laser ablation and conservative management with regular follow up [8]. Novel treatments for women preferring not to have surgery have been investigated and include therapeutic vaccination, photodynamic
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T.S. Shylasree et al. / Gynecologic Oncology 110 (2008) 185–189
therapy and topical treatment with imiquimod and cidofovir, with variable results [9–16]. Health related QoL (HR-QoL) is a multidimensional, patient centred concept. It encompasses physical health and symptoms, functional status, mental well being and social functioning. Four aspects of VIN might be predicted to impact on quality of life (QoL): potential for malignant progression or recurrence: symptoms: side effects of treatment and its association with human papillomavirus (HPV), which is sexually transmitted. Four studies have looked at sexual dysfunction and quality of life following surgery in women with VIN [17–20] {Literature search conducted using electronic databases: Medline (1966 to present), CINAHL (1982 to present), Cochrane DSR, database of abstracts of reviews of effectiveness (DARE), CCTR, CMR, HTA and NHSEED using key words: vulval intraepithelial neoplasia, quality of life, sexual dysfunction, outcomes following surgery for VIN}. There are currently no disease-specific QoL measurement tools for VIN. The goals of this study were to • Quantify the effect of demographic, psychological and diseaserelated factors in women with high-grade VIN on general and emotional health, body image and sexual health as measured by existing instruments. • Obtain qualitative data exploring the effect of disease and treatment on these women and the reasons for sexual inactivity or discontent and the effect of disease on partners. • Assess the participants' perception of their risk of developing of vulval cancer and its relation to QoL outcomes. Methods Approval for the study was obtained from the South East Wales Research Ethics Committee and Whittington Research Ethics Committee, United Kingdom.
Participants Women who had attended one of two UK specialist VIN clinics were recruited. Questionnaires were sent to 100 patients from Cardiff and Vale NHS
Table 1 Relevant SF 12 questions on general, emotional health and body image Questions about general health (5 responses) In general, would you say your health is now? Did your symptoms/health interfere with your usual activities? Did your symptoms/health interfere with your sleep? Did your symptoms/health interfere with your social life? Did your symptoms/health interfere with your holidays and outings? Questions about your feelings and emotions (3 responses) How much have your emotions or feelings interfered with your 1) Work or other regular activities 2) Social activities 3) Holidays and outings Questions on body image (five responses) Have you been feeling self-conscious about your appearance? Have you felt less physically attractive as a result of your disease? Have you been feeling less feminine as a result of your disease? Have you been feeling less sexually attractive as a result of disease? Have you been dissatisfied with your body?
Table 2 Sexual self-rating Sabbatsburg questionnaire (5 responses) My interest in sex during last month has been In comparison to previous years my interest in sex is now My sexual activity during the last month has been In comparison to previous years my sexual activity is now My sex life during the last month has been In comparison to previous years my sex life is now Sex during the last month has given me In comparison to previous years sex now gives me My ability to reach orgasm during the last month has been In comparison to previous years my ability to reach orgasm has been Sex is for me: In comparison to previous years the importance of sex has for me
Trust, Cardiff and 50 patients from the Royal Free Hospital, London in October 2005. A reminder letter was sent two months later to non-responders.
Instruments A questionnaire was constructed to quantify the demographic, psychological and disease-related factors to be assessed and the effect of these factors on QoL outcomes (general health, emotional health, body image and sexual health). Demographic data collected included questions on age, living status and smoking history. Living status was divided into three groups: single/living alone, married/living with partner, separated/divorced/widowed. Psychological status was measured using the standard Hospital Anxiety and Depression Scale (HADS) [21]. HADS is a 14-item scale, with 7 questions assessing anxiety (HADS-A) and 7 assessing depression (HADS-D). Total scores for each part range from 0–21: a score of less than 7 is considered normal, between 8–10 indicates possible clinical levels of anxiety or depression and a score of 11 or above indicates definite clinical anxiety or depression. Disease-related questions recorded the time since first diagnosis, symptoms at initial presentation, treatment history and participation in VIN research trials. Participants were also asked to estimate their risk of developing vulval cancer on a scale of 0–100% and the results were correlated with the QoL outcomes. Four aspects of QoL were measured: general health, emotional health, body image and sexual health. Questions on general health, emotional health and body image were constructed using relevant questions from the twelve item short form health survey (SF12) [22], (Table 1). Sexual health was measured using the revised Sabbatsburg self-rating questionnaire [23] (Table 2). This questionnaire has 12 questions with scores ranging from 0–60, with 60 denoting maximum sexual activity. Free text comments were invited regarding women's perception of the effect the disease had on their partners, the reasons for sexual inactivity or discontent and the effects of treatment, with a final section for any additional comments. The questionnaire was initially piloted amongst 10 women attending VIN clinics on both sites and alterations made for clarity.
Statistics The effects of demographic, psychological and disease-related factors on the four different QoL outcomes (general health, sexual health, body image and emotional health) were calculated using the general linear model analysis technique and multiple pair wise comparisons (adjusted for Bonferroni correction) using SPSS version12 software. A p-value of 0.05 was considered to indicate the level of statistical significance.
Results Descriptive statistics Demographic factors Of the 150 women invited to participate in the study, 82 responded (54.6%). The median age was 48 years (range 26–
T.S. Shylasree et al. / Gynecologic Oncology 110 (2008) 185–189 Table 3 Results of HADS for women with VIN (n = 82)
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Box 1 Free text comments on the impact of VIN on quality of life
HADS
Anxiety
Depression
None (score 0–7) Mild (score 8–10) Moderate (score 11–14) Severe (15–21)
45% 17% 16% 16%
54% 24% 12% 6%
81) and 35 (43%) were current smokers. Forty-four (53.6%) of the respondents were sexually active. Nineteen (23%) were single or lived alone, forty-four (54%) were married or lived with a partner, and nineteen (23%) were separated or divorced or widowed. Psychological factors The mean and median scores for HADS anxiety was 8 and HADS depression 6. Thirty two percent of the study group had moderate to severe anxiety and 18% had moderate to severe depression, (Table 3). Disease-related factors VIN had been diagnosed more than 5 years, prior to the study in 35 women (42.6%). Of the 68 women (83%) who were symptomatic at the time of presentation, 58 (85%) had vulval itching and 39 (57%) vulval pain. Nine patients (11%) answered that they were managed conservatively after biopsy diagnosis, thirty four (41.4%) had one form of treatment, twenty five (30.4%) had two and seven (8.5%) had received more than two forms of treatment. Twenty five patients (30.4%) had participated in research trials involving VIN. The perceived risk of developing vulval cancer is shown in Table 4. Correlates with patient demographics Age had an effect on emotional health (p = 0.02), such that increasing age led to worsening emotional health. When living status was examined by multiple pair wise comparisons, there was a significant difference between women who were single/ living alone and those who were separated/divorced/widowed with the latter group having better body image (p = 0.014 adjusted for Bonferroni correction) and better emotional health (p = 0.025 adjusted for Bonferroni correction).
I suffer from depression, compassion and a female nurse would help. I was diagnosed in my first pregnancy and am worried that it may recur in my next pregnancy. I feel that I have a dirty disease that has affected me emotionally and physically. I find it hard that VIN is sex related and I haven't had sex for many years. Celibacy is simpler, for fear of infecting a partner. I have stopped wearing trousers, VIN has affected my confidence and I no longer feel sexually attractive. I am very fortunate that I can have regular checkups. I am worried about my daughter getting the same problems. Wearing clothes is difficult. We need help to improve sex drive and soreness.
and depression levels led to worsening general health (HADS-A p b 0.01, HADS-D p b 0.01) emotional health (HADS-A pb 0.001, HADS-D pb 0.01) and body image (HADS-A p b 0.001, HADS-D p b 0.01). For sexual health, an increase in HADS depression led to worsening sexual health (HADS-D p b 0.01) whereas HADS anxiety (HADS-A p= 0.093) did not have a significant effect. Correlates with disease-related status The presence or absence of symptoms, duration of VIN, number of treatments and participation in research trials did not have a significant effect on any of the outcomes of QoL. There was a significant positive association between a perceived risk of developing vulval cancer of 10% or greater with worsening general and emotional health (p = 0.001, p = 0.002 Spearman's rho = 0.41 respectively). Body image and sexual health were not associated with the women's perception of developing vulval cancer. Qualitative data
Correlates with psychological status The effect of both HADS scores (HADS-A and HADS-D) on the outcomes of QoL was such that an increase in the anxiety
Table 4 Estimated risk of developing vulval cancer Estimated risk of developing vulval cancer
Number of women n
%
0–10% 11–50% 51–90% 91–100% Did not give a figure
15 27 13 4 23
18 33 16 5 28
There was a broad range of comments on the impact of VIN on quality of life with examples shown in text box 1. Thirty six women gave free text comments on the effect of various treatments; of which twenty six women said that the most common side effect of surgery, laser and topical applications was pain. One woman said that she ‘had a very tiring time because of various treatments’ and another said that she was ‘very young and was traumatised by surgery’. There was a comment on a lack of sensation after surgical excision. There were three positive comments about surgical excision where the procedure had eradicated symptoms. One participant wrote a separate 2 paged letter along with the completed questionnaire saying that she had ‘suffered a great deal because of this wretched disease’ and after trying almost every
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treatment available for VIN she had come to terms with the disease. She felt that the last few years had been better as the course of the disease and its treatment was being researched by the medical fraternity. Twenty one women gave reasons for being sexually inactive and 33 women for being sexually unhappy. Common reasons for being sexually inactive, unhappy or less satisfied were soreness or pain, fear, self consciousness, older age, lack of sex drive, no current partner and fear of passing on the virus or disease. Thirty five women (56%) with current or previous partners answered the question on their partner or husband being affected by the disease. There was a wide range of comments about partners being affected. Seven women said their partners were supportive, accepting or understanding although one wrote ‘constant support, but our marriage has suffered, with many tears and feelings of failure’. The majority said that their relationship had suffered in some way. One woman said “My previous partner left, he said it was better to die”, another that “I have pushed him to the edge by crying and moaning”. Discussion This study examined the effect of demographic, psychological and disease-related factors on the QoL outcomes of women attending two specialist VIN clinics in the UK, to quantify their effect upon general, emotional and sexual health including body image as measured by existing instruments. Demographic factors were shown to affect some aspects of QoL in our study. Poorer quality of life was associated with increasing age and being single with worse emotional health and body image. Poorer sexual function and QoL has been noted in older women undergoing surgical excision of VIN in other studies [19]. Depression affected all aspects of health in the present study. Loss of libido and poor body image are important depressive symptoms and indicate that women with VIN are vulnerable to psychological morbidity. Anxiety affected general and emotional health as well as body image but did not have an effect on sexual health in this study. Studies in women with vulvodynia have shown high levels of depression and anxiety; depression being more prominent than anxiety [24,25]. Clinical variables such as duration of disease, presence of symptoms and the number of treatments did not have a measurable impact on QoL. The patient response rate in our study was 54.6% which is good for a postal based questionnaire study, although nonresponse might introduce bias either way. One limitation of the study was that the cross-sectional research design did not permit examination of a possible sequential relationship between clinical variables affecting QoL or causing psychological morbidity. Further study is required to assess how best to address longitudinal study of women with VIN. This study show, however that psychological morbidity is highly prevalent in VIN patients. The conventional management of women with VIN is by surgical excision of affected tissue. In the systematic review of 3322 VIN3 patients, 1921 women were treated surgically [1]. The difficulty arises when the disease is multifocal, multicentric and persistent, when extensive surgery is required that will alter
the cosmetic appearance and functional capacity of the vulva and in turn will have significant effects on QoL. It has been shown that up to a half of patients suffer both sexual dysfunction and psychological problems following radical and simple vulvectomy [8,26]. The magnitude of excision has been shown to be proportional to somatopsychic reactions and sexual dysfunction, [27,19]. Women also indicated their wish to receive information related to sexual functioning and felt it should also be available to their partner [8]. Novel forms of treatment such as imiquimod and cidofovir are associated with significant short term side effects, but preserve the anatomy and functional aspects of the vulva [15,28].There are no long term data on disease recurrence or progression with these forms of treatment. In the present study, all forms of treatment had adverse side effects on patients, pain being the predominant side effect. The anatomical extent of the disease and treatment failure was not evaluated in our study making comparisons between various treatments difficult. The appropriate management of VIN is still evolving and the various treatment modalities have emerged over time. The lack of larger studies comparing the effect of various treatments for VIN on QoL should be an area for future research. The reasons given for sexual inactivity and sexual unhappiness indicate a significant interaction between demographic, psychological and disease-related factors affecting individuals differently. Women who have other chronic genital disorders will often lose their interest in sexual activity leading to problems with sexual dysfunction, [29,30]. It has been suggested that it is important to give these women the opportunity to express their concerns regarding sexual functioning and to offer support with the necessary expertise to address such problems [31]. The women's perception of their partners' reaction to VIN was negative on the whole. Examining whether this was a true reflection of the situation was not part of this study, but would be important in order to address the issues raised. Studies on vulval vestibulitis have shown similar effects of disease on partners to those found in the present study [32]. The women's perception of the likelihood of developing vulval cancer increased with worsening general and emotional health. Catastrophizing is the tendency to overemphasize the probability and possible consequences of a catastrophic outcome and has been shown to be related to anxiety [33]. This needs to be addressed by giving women accurate information. There is currently no validated quality of life assessment tool for use in women with VIN. The findings of this study will assist the construction of VIN-specific QoL instruments in future, which can be used in trials comparing treatments for VIN. Summary Women with VIN experience significant psychological morbidity. Psychological factors and to some extent demographic factors were much stronger determinants of QoL in women with VIN compared to clinical factors. Multidisciplinary management of these women should therefore be considered in order to take into account the psychological co-morbidity. Accurate written information should be provided about the risk of developing invasive disease.
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Further research is needed to establish a VIN-specific instrument to measure quality of life, the benefit of multidisciplinary input and the true impact of VIN on partners. Conflict of interest statement The authors declare that they have no conflicts of interest to disclose.
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