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Significance of Human Papillomavirus (HPV) Analysis for the Detection of Precancerous Cervical Lesions: Impact of Self Sampling
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cervical cancer is the second most common cancer, with about 500 000 new cases per year among women worldwide. With a well-organized screening programme the number of cases can be reduced by more than 50%. In spite of having such a screening programme there are still around 450 new cases yearly in Sweden. The majority of these cases occur in non-attendees. There is thus a need to improve the Swedish cervical cancer screening programme in order to further reduce the number of cases of cervical cancer.

Cervical cancer and high-grade cervical dysplasia are caused by sexually transferred high-risk human papillomaviruses (HR-HPVs). In cases of persistent HR-HPV infection there is a risk of development of dysplasia and in some cases subsequent progress to cervical cancer. HR-HPV testing shows high sensitivity as regards the detection of cervical dysplasia. Self-sampling of vaginal fluid for the analysis of HR-HPV has many advantages, since a woman can perform the sampling herself in a private setting, whenever suitable, without the need to travel to a clinic.

Our studies have shown that sensitivity in the detection of precancerous lesions is about twice as great with the HR-HPV self-test compared with cytology-based tests.  If a woman was HR-HPV-positive in two consecutive tests, the specificity of the HR-HPV test increased to about 98%. Among women with short-term persistent HR-HPV infection, the prevalence of CIN 2+ was over 40%. There was good concordance in sensitivity as regards the detection of CIN 2+ between self-obtained and physician-obtained samples, although self-sampling was associated with slightly lower specificity.

The prevalence of HR-HPV from day to day in premenopausal women was not influenced by hormonal changes during the menstrual cycle. Neither were there significant day-to-day changes in postmenopausal women. A single self-test thus provides reliable information on whether or not a woman has an HR-HPV infection.

In conclusion, self-sampling combined with the analysis of HR-HPV appears to be a powerful alternative as a primary screening method for the prevention of cervical cancer. Self-sampling for HR-HPV testing is a suitable, safe and accepted strategy for cervical cancer prevention among women.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 63 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 877
Keyword [en]
human papilloma virus, HPV, self-sampling, organized screening, cervical cancer screening
National Category
Medical and Health Sciences
Research subject
Obstetrics and Gynaecology
Identifiers
URN: urn:nbn:se:uu:diva-196873ISBN: 978-91-554-8621-1 (print)OAI: oai:DiVA.org:uu-196873DiVA: diva2:611041
Public defence
2013-05-03, Auditorium Minus, Guatavianum, Akademigatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2013-04-11 Created: 2013-03-14 Last updated: 2014-08-15Bibliographically approved
List of papers
1. Self-sampling of the vaginal fluid at home combined with high-risk HPV testing
Open this publication in new window or tab >>Self-sampling of the vaginal fluid at home combined with high-risk HPV testing
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2009 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 101, no 5, 871-874 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Around 65% of women with cervical carcinoma in Sweden have not attended an organised screening. We therefore investigated the value of using self-sampling at home in combination with a test for high-risk human papilloma virus (HPV) to increase participation. METHODS: A total of 2829 women 30-58 years old, who had not attended the organised screening for > or = 6 years, were recruited. They were offered self-sampling at home (Qvintip) and recommended to send the collected vaginal fluid to a laboratory for analysis of the presence of high-risk HPV (Hybrid Capture 2 method). RESULTS: A total of 39.1% of the women accepted home sampling. These women disclosed a relatively high prevalence of high-risk HPV, which decreased with age, from 11.1% in women 30-39 years old to 2.9% in women > or =50 years . Follow-up disclosed histological cervical intraepithelial neoplasm (CIN) 2-3 lesions in 43.2% of the women with a persistent HPV infection, corresponding to 2.0% of the total number of participating women. The sensitivity of a single smear to detect the histological CIN 2-3 lesions were only 52.6%, even if all abnormal smears (atypical squamous cells of unknown significance (ASCUS)-CIN 3)) were included. CONCLUSION: The use of self-sampling at home in combination with testing for high-risk HPV increases the participation rate of the organised screening and detects almost twice as many women with pre-malignant cell alterations (CIN 2-3) in comparison those with a single cytological smear.

Keyword
cervix, cytology, screening, HPV test, self-sampling
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-111819 (URN)10.1038/sj.bjc.6605194 (DOI)000269312800019 ()19654577 (PubMedID)
Available from: 2009-12-22 Created: 2009-12-22 Last updated: 2017-12-12Bibliographically approved
2. Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer
Open this publication in new window or tab >>Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer
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2011 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 105, no 5, 694-697 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30-65 years, with the primary sample for HPV analysis taken by self-sampling. METHODS: A total of 8000 women in Uppsala County, aged 30-65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test. RESULTS: In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18-30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31-51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30-39 years to 24% in women at age 50-65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%). CONCLUSION: The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30-65 years.

Keyword
cervix, screening, carcinoma, HPV test, persistence, self-sampling
National Category
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-158900 (URN)10.1038/bjc.2011.277 (DOI)000294207800015 ()21811250 (PubMedID)
Note

First two authors contributed equally to this work.

Available from: 2011-09-19 Created: 2011-09-19 Last updated: 2017-12-08Bibliographically approved
3. Type-specific detection of high-risk human papillomavirus (HPV) in self-sampled cervicovaginal cells applied to FTA elute cartridge
Open this publication in new window or tab >>Type-specific detection of high-risk human papillomavirus (HPV) in self-sampled cervicovaginal cells applied to FTA elute cartridge
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2011 (English)In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 51, no 4, 255-258 p.Article in journal (Refereed) Published
Abstract [en]

Background

Most procedures for self-sampling of cervical cells are based on liquid-based media for transportation and storage. An alternative is to use a solid support, such as dry filter paper media.

Objectives

To evaluate if self-sampling of cervicovaginal fluid using a cytobrush (Viba-brush; Rovers Medical Devices B.V., Oss, The Netherlands) and a solid support such as the Whatman Indicating FTA® Elute cartridge (GE Healthcare, United Kingdom) can be used for reliable typing of human papillomavirus (HPV), as compared to cervical samples obtained by a physician using a cytobrush and the indicating FTA® Elute Micro card and biopsy analysis.

Study design

A total of 50 women with a previous high-risk (HR) HPV positive test were invited to perform self-sampling using the Viba-brush and the FTA cartridge and thereafter a physician obtained a cervical sample using the cytobrush and a FTA card, together with a cervical biopsy for histology and HPV typing. Detection of HR-HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 was performed using three multiplex real-time polymerase chain reaction (PCR) assays.

Result

All samples contained sufficient amounts of genomic DNA and the self-samples yielded on average 3.5 times more DNA than those obtained by the physician. All women that were positive for HR-HPV in the biopsy sample also typed positive both by self-sampling and physician-obtained sampling. For women with a histological diagnosis of cervical intraepithelial neoplasia grades 2–3 (CIN 2–3) all three HPV samples showed 100% concordance. A higher number of women were HPV positive by self-sampling than by physician-obtained sampling or by biopsy analysis.

Conclusion

The Viba-brush and the FTA cartridge are suitable for self-sampling of vaginal cells and subsequent HR-HPV typing.

Keyword
Self-sampling, FTA cartridge, Cervical carcinoma, Human papillomavirus (HPV), Real-time polymerase chain reaction (PCR)
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-156562 (URN)10.1016/j.jcv.2011.05.006 (DOI)000292507700008 ()21632283 (PubMedID)
Available from: 2011-08-03 Created: 2011-08-03 Last updated: 2017-12-08Bibliographically approved
4. Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing
Open this publication in new window or tab >>Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing
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(English)Manuscript (preprint) (Other academic)
Keyword
self-sampling. human papillomavirus, HPV
National Category
Medical and Health Sciences
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-195966 (URN)
Available from: 2013-03-01 Created: 2013-03-01 Last updated: 2013-08-30

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