Attitudes to self-sampling of vaginal smear for human papilloma virus analysis among women not attending organized cytological screening

Transcription

1 Acta Obstetricia et Gynecologica. 2007; 86: ORIGINAL ARTICLE Attitudes to self-sampling of vaginal smear for human papilloma virus analysis among women not attending organized cytological screening INGRID WIKSTRÖM, HARRIET STENVALL & ERIK WILANDER Department of Women s and Children s Health, Section for Obstetrics and Gynaecology and Department of Genetics and Pathology, University Hospital of Uppsala, Sweden Abstract Background. The major problem with the cytological screening is the non-optimal participation rate among women invited for cervical smear collection. The aim of the present investigation was to examine the attitudes of the non-responding women to perform self-sampling of vaginal smear at home as a method to increase the coverage of the screening and to examine the prevalence of high-risk human papilloma virus (HPV) among the responding women. Methods. From the database of the Department of Cytology, University Hospital of Uppsala 198 women, aged 3555 years, who had not attended the organized gynaecological screening for over 6 years were identified. They were sent a letter of information about the study and one week later a self-sampling device aimed to collect vaginal smear. The vaginal smear of the women responding to the offer of self-sampling was analysed for high-risk HPV using Hybrid Capture 2 method or polymerase chain reaction amplification of HPV DNA. All women in the study also received a questionnaire in order to investigate their attitudes towards self-sampling as an alternative in the organized screening. Results. Of the 198 women 15 women had to be excluded. Fifty-eight per cent of the women responded and collected vaginal smear at home and among them 7% were positive for high-risk HPV. The questionnaire revealed no significant difference of age, country of birth and occupation or marital status, on using self-sampling of vaginal smear at home. The attitudes among responding and non-responding women differed. The responding women who contributed by sampling vaginal smear were more positive to self-sampling of vaginal smear (pb0.01). Conclusions. Offering self-sampling of vaginal smear in women not attending the organized cytological screening increases the coverage and identifies an additional group of women with an increased risk to develop cervical cancer. The attitude towards self-sampling was mainly positive. Key words: Self-sampling, vagina, smear, HPV test, gynecological screening Abbreviations: PCR: polymerase chain reaction, SSD: self-sampling device, HPV: human papillomavirus, DNA: deoxyribonucleic acid, CIN: cervical intraepithelial neoplasia, HC 2: hybrid capture 2, GP 5: general primer 5, GP6: general primer 6 Persisting high-risk human papilloma virus (HPV) and cervical intraepithelial neoplasia (CIN) are considered a necessary event preceding cervical cancer (1 3). The gynecological screening launched in Sweden almost 40 years ago has decreased the prevalence of cervical cancer by about 50% (4). At present, about 50% of women diagnosed with cervical cancer have chosen not to participate in the organized screening or are, due to age (60 years), not covered by the program (5). Without question, the current major problem with the cytological screening is the nonoptimal participation rate among women who are invited for smear collection (6,7). To improve this situation, a self-sampling device (SSD) was developed. It permits women to selfsample a vaginal smear at home. The collected material is then sent to a laboratory for high-risk HPV analysis. Pilot studies in a gynecological reception have shown that the SSD collects a vaginal smear of similar quality to a cervical smear collected with cytobrush (Scanmed, Medical, Correspondence: Ingrid Wikström, Department of Women s and Children s Health, Section for Obstetrics and Gynaecology, University Hospital, S Uppsala, Sweden. Ingrid.Wikstrom@kbh.uu.se (Received 26 February 2007; accepted 27 February 2007) ISSN print/issn online # 2007 Taylor & Francis DOI: /

2 Attitudes to self-sampling of vaginal smear 721 Malmö, Sweden) by a gynecologist, when analyzed for the presence of high-risk HPV DNA using the hybrid capture 2 (HC 2) technique (8). In addition, more women were high-risk HPV positive than cytologically abnormal, in the previous study (9). This observation encouraged an additional study in which the SSD was sent by mail to the home address of women who had chosen not to respond to an invitation to smear collection within the frame of the organized cytological screening in the county of Uppsala, Sweden. Material and methods The County of Uppsala, Sweden has 300,000 inhabitants, of which 50% are women. 70,000 of those women are within the age range of years and are included in the organized cytological screening, where women are invited by letter for smear collection at a nurse reception every third year. Over 20,000 cervical smears are screened every year and all information of the organized screening is collected in a central database (Sym- Pathy, Informationslogik, Malmö, Sweden, Department of Cytology, University Hospital of Uppsala). From this central database, 198 women, aged years, who had not participated in the organized cytological screening for over 6 years were identified. The women were sent a letter saying that they were going to be offered the possibility of selfsampling of vaginal smear at home and that the collected material was to be sent to a laboratory for analysis of the presence of high-risk HPV. They were also informed that they were selected because they had chosen to not utilize the organized screening service. Furthermore, the information letter described the importance of HPV infection for the development of premalignant cell alterations on the cervix. Of these 198 women, 13 women had to be excluded because of unknown address and two women were excluded because of a previous hysterectomy. One week later a SSD (Qvintip, Aprovix AD, Uppsala, Sweden) was sent to the remaining 183 women. HPV DNA analysis The vaginal smear of the women responding to the offer of self-sampling was analyzed for high-risk HPV using Hybrid Capture 2 (HC 2, Digene Corporation, Gaithersburg, MD, USA) method and polymerase chain reaction (PCR) amplification of HPV DNA. Vaginal smears arriving at the cytological laboratory were analyzed using the HC 2 technique (33 cases). The material was transferred to a transport medium and then analyzed for the presence of high-risk HPV according to the manufacturer s instructions (10). Smears were also analyzed using a PCR enzyme immunoassay mediating PCR with general primers GP5 and GP6 (73 cases) (11). When the HPV analysis was completed the women participating in the study were sent a letter of information about their test results. Women with a positive HPV test were recommended to get in contact with a nurse reception or a gynecologist for further examination. Questionnaire To investigate the women s attitudes towards the home-test kit all women recorded on the participation list received a questionnaire, together with a reminder, two months later. The questionnaire consisted of questions about age, country of birth, occupation, marital status, children, knowledge about HPV, and their experience of using the Qvintip kit for self-sampling of vaginal smear. To investigate differences in background factors and attitudes towards the home test between responders and non-responders we used the Fisher s exact test, which tests the independence between response status and the variables in the questionnaire. Results Response rate Fifty-eight per cent (106/183) of the women responded and collected a vaginal smear at home. In Table I the response time is shown. Among them 7% (7/106) were positive for high-risk HPV (Table II). Of these 7 women who were recommended for further examination, 5 underwent pap smear testing and one woman a re-testing for HPV, using regular cytobrush for smear collection. From two of the 7 women a cervical biopsy was obtained. One of these Table I. Response time in women accepting to perform selfsampling of vaginal material at home. Time Response rate (%) 3 weeks 45 5 weeks 62 7 weeks weeks 100

3 722 I. Wikström et al. Table II. Response rate and HPV prevalence in women offered self-sampling of vaginal smear at home. Number of participating women 183 Number of women using SSD* 106/183 58% Non-responders 77/183 42% HPV-positive women 7/106 7% *SSD, self-sampling device. women showed a CIN III lesion and one woman was diagnosed with a squamous cell cervical carcinoma (Table III). Questionnaire Of 185 women receiving the questionnaire, 124 (67.0%) responded (Table IV). One woman who did not give information on whether she had taken a home sample or not was excluded from the analysis. Most of the women returning the questionnaire were those who also conducted the home sampling: 94 (89%) of 106 women. Only 29 (38%) of the 77 women who did not use the SSD returned the questionnaire (Table IV). We did not find any differences in background factors between respondents and non-respondents to the home sampling. However, a larger proportion of the respondents than the non-respondents preferred to take the test at home (82% versus 31% respectively), whereas a larger proportion of the nonrespondents preferred to have the test taken at a clinic by a gynecologist or a midwife (31%). A larger proportion of the respondents compared to the nonrespondents also stated they were likely to take a home sample in the future (94% versus 48%, respectively), and that they believed that it is valuable to take an HPV test (95% versus 76%, respectively) (Table IV). Table III. Follow-up at clinic of 7 women who were shown to be high-risk HPV positive after self-sampling for vaginal smear at home. Case no. Pap-smear HPV test result PAD 1 Normal None 2 Normal None 3 None 4 ASCUS Positive CIN III* 5 Normal None 6 Cervical cancer** 7 Normal None *This woman was treated with a conization. **This woman was diagnosed with cervical carcinoma after being admitted to hospital due to clinical symptoms of vaginal bleeding. The most common answers to why non-respondents did not use the home sample were that they believed that they did not need the test (38%), mainly as they had either taken a test recently, they had had a hysterectomy, or they did not think they were at risk of getting HPV (38%). The second most common answer of the nonrespondents was that they wanted a private gynecologist or a midwife to take the test (24%), as they either felt insecure about taking the test themselves or they had other issues to discuss and wanted to be able to ask questions. The most mentioned benefits of the home sample for the respondents were that it was easy for practical reasons (no time limits, that they did not have to book time or travel) (93%), time saving (29%), and emotionally easier as they did not have to undergo a gynecological examination (22%). Both responders and non-responders felt uncertain if they had taken, or could take, the sample appropriately (22% and 38%, respectively). Discussion A previous study in Sweden of healthy middle-aged women showed a prevalence of high-risk HPV infection in 6.8% of the population (12). Our investigation, comprising older women, showed a prevalence of high-risk HPV in vaginal smear obtained by self-collection at home in accordance with that investigation. This may indicate that the population of women who chose not to participate in the organized screening program or because of age (over 60 years) are not included in the program can be identified as risk individuals to develop cervical cancer. As the relative risk of HPV infection decreases with age, it is possible that nonparticipating women more often are HPV infected than those accepting a smear collection at a midwife reception. The value of offering the SSD for self-sampling of a vaginal smear at home is related to the attitudes and response rate of the women, which in this study was considered as high, over 50%. In another study we offered 369 women (aged years) who had not attended organized cytological screening for more than 6 years to order the SSD by post and observed a lower response rate, with 32% of the women returning their samples for analysis. The method of distributing the SSD directly to all women concerned therefore seems to be more efficient (13). The acceptance of self-collecting of a vaginal smear has been studied before and is reported to be high (14 16). However, these investigations are all based on women participating in the organized screening or present in a gynecological reception. As

4 Attitudes to self-sampling of vaginal smear 723 Table IV. Questionnaire results. Respondents Non-respondents Number % Number % p-value 1 Total Age NS No answer Country of birth Sweden NS Other No answer Occupation Employed/student NS Unemployed/ housewife Retired/Disability pension No answer Marital status Married/Partner NS Other No answer Children Yes NS No No answer Prefer to take a HPV test At home *** At a gynecologist/midwife/reception Does not matter Does not know No answer Likelihood to take a home sample in the future Very/fairly likely *** Not likely Does not know No answer Likelihood to attend after an invitation Very/fairly likely NS Not likely Does not know No answer Value of taking a HPV-test Very/fairly valuable ** Not valuable Does not know No answer Own risk of having HPV Greater/same as others NS Less than others Does not know No answer p-values from a Fisher s exact test, testing the independence of the response groups and background factors, preferences, and attitudes. *50.05, **50.01, *** far as we know our study is the first conducted on a selected group of women who have refused to respond to the invitation for smear collection. A major weakness with the questionnaire study is that only a few of the non-respondents chose to return the questionnaire. Precision of the statistical

5 724 I. Wikström et al. test is affected negatively and there is a risk of response-bias. The results do, however, indicate that the respondents use the home sample for both practical and emotional reasons whereas the nonrespondents feel insecure about both their own ability to take the sample appropriately and the value of HPV testing. As about 50% of all cancer cases in Sweden occur in women who have a prior history of non-participating in the screening, an acceptance rate of over 50% for self-collection of vaginal smear at home seems to be a useful adjunct to increase the coverage in the organized screening and to cause a noticeable decrease in the incidence of cervical cancer. Several studies have shown that there is agreement between HPV test results obtained by self-sampling of vaginal smear and physician-directed samples of cervical smear (16 20). Consequently, there seems to be no reason for objection against self-sampling when HPV tests are used as a tool in the organized screening program. A review of the literature shows that when comparing regular cytology with HPV analysis, most studies show that HPV tests are more sensitive whereas the specificity of the two methods is about equal (21 24). There seems to be no adequate arguments against using self-sampling and HPV tests as a reliable method in the screening for risk individuals for cervical cancer, especially when the method is directed towards women who have chosen not to respond to an invitation for cervical smear taking. Generally the participants of the study thought that the self-sampling was easy to perform, the manual gave adequate information, and that the sampling was without pain. The questionnaire answers show self-sampling at home to be an attractive method for screening in the future. Acknowledgements This study was approved by the Ethical Committee of Uppsala (Dnr. 2004:M-202) and the Board of Cervical Cancer Screening in the County of Uppsala. The study was supported by the Medical Faculty of Uppsala and by the Lion Cancer Foundation of Uppsala. The technical assistance of Ingrid Backlund is appreciated. References 1. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;/189:/ zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;/2:/ Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al. International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;/348:/ Socialstyrelsen, Sos-rapport Gynekologisk cellprovskontroll Förslag till screeningprogram [The National Board of Health and Welfare. Report: Cytological Screening for Cervical Cancer Screening Programme Suggestion] (In Swedish) Article Number 1998; Eaker S, Adami HO, Granath F, Wilander E, Sparen P. A large population-based randomized controlled trial to increase attendance at screening for cervical cancer. Cancer Epidemiol Biomarkers Prev. 2004;/13:/ Stenkvist B, Söderström J. Reasons for cervical cancer despite extensive screening. J Med Screen. 1996;/3: / Eaker S, Adami HO, Sparen P. Reasons women do not attend screening for cervical cancer: a population-based study in Sweden. Prev Med. 2001;/32:/ Stenvall H, Wikström I, Wilander E. Human papilloma virus testing of vaginal smear obtained with a novel self-sampling device. Acta Derm Venereol. 2006;/86:/ Stenvall H, Wikström I, Backlund I, Wilander E. Accuracy of HPV testing of vaginal smear obtained with a novel selfsampling device. Acta Obstet Gynecol. 2007;/86:/ Digene Corporation Hybrid Capture Technology HC 2. Available on WWW at Accessed 3 June Jacobs MV, Snijders PJ, van der Brule AJ, Helmerhorst TJ, Meijer CJ, Walboomers JM. A general primer GP5/ GP6()-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol. 1997;/35:/ Forslund O, Antonsson A, Edlund K, van der Brule AJ, Hansson BG, Meijer CJ, et al. Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish women. J Med Virol. 2002;/67:/ Stenvall H, Wikström I, Wilander E. High prevalence of oncogenic HPV in women not attending organized cytological screening. Acta Derm Venereol. 2007;87: Dannecker C, Siebert U, Thaler CJ, Kiermeir D, Hepp H, Hillemanns P. Primary cervical cancer screening by selfsampling of human papillomavirus DNA in internal medicine outpatient clinics. Ann Oncol. 2004;/15:/ Dzuba IG, Diaz EY, Allen B, Leonard YF, Lazcano Ponce EC, Shah KV, et al. The acceptability of self-collected samples for HPV testing vs. the pap test as alternatives in cervical cancer screening. J Womens Health Gend Based Med. 2002;/11:/ Nobbenhuis MA, Helmerhorst TJ, van der Brule AJ, Rozendaal L, Jaspars LH, Voorhorst FJ, et al. Primary screening for high risk HPV by home obtained cervicovaginal lavage is an alternative screening tool for unscreened women. J Clin Pathol. 2002;/55:/ Harper DM, Noll WW, Belloni DR, Cole BF. Randomized clinical trial of PCR-determined human papillomavirus detection methods: self-sampling versus clinician-directed biologic concordance and women s preferences. Am J Obstet Gynecol. 2002;/186:/ Brink AA, Meijer CJ, Wiegerinck MA, Nieboer TE, Kruitwagen RF, van Kemenade F, et al. High concordance of results of testing for human papillomavirus in cervicovaginal samples

6 Attitudes to self-sampling of vaginal smear 725 collected by two methods, with comparison of a novel selfsampling device to a conventional endocervical brush. J Clin Microbiol. 2006;/44:/ Agorastos T, Dinas K, Lloveras B, Font R, Kornegay JR, Bontis J, et al. Self-sampling versus physician-sampling for human papillomavirus testing. Int J STD AIDS. 2005;/16:/ Gravitt PE, Lacey JV Jr, Brinton LA, Barnes WA, Kornegay JR, Greenberg MD, et al. Evaluation of self-collected cervicovaginal cell samples for human papillomavirus testing by polymerase chain reaction. Cancer Epidemiol Biomarkers Prev. 2001;/10:/ Nanda K, McCrory DC, Myers ER, Bastian LA, Hasselblad V, Hickey JD, et al. Accuracy of the Papanicolau test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med. 2000;/132:/ Clavel C, Masure M, Bory JP, Putaud I, Mangeonjean C, Lorenzato M, et al. Hybrid Capture II-based human papillomavirus detection, a sensitive test to detect in routine highgrade cervical lesions: a preliminary study on 1518 women. Br J Cancer. 1999;/80:/ Cuzick J, Sasieni P, Davies P, Adams J, Normand C, Frater A, et al. A systematic review of the role of human papilloma virus (HPV) testing within a cervical screening programme: summary and conclusions. Br J Cancer. 2000;/83:/ Pontén J, Adami HO, Bergstrom R, Dillner J, Friberg LG, Gustafsson L, et al. Strategies for global control of cervical cancer. Int J Cancer. 1995;/60:/126.