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Aarnio, Riina
Publications (10 of 11) Show all publications
Aarnio, R. (2020). Self-sampling for HPV testing in primary cervical screening: Including clinical and health economic aspects. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Self-sampling for HPV testing in primary cervical screening: Including clinical and health economic aspects
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Persistent infection with high-risk human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. HPV testing has higher sensitivity for high-grade cervical intraepithelial neoplasia (CIN2+) than cytology, resulting in more effective screening. As HPV testing also offers an opportunity for self-sampling, it could serve as an even more effective and cost-effective method of cervical screening.

First, we compared repeated self-sampling for HPV testing with Pap smear cytology in detection of CIN2+ in primary cervical screening for women aged 30–49 years (n=36 390). We found a more than twofold higher detection rate of CIN2+ and a fourfold higher detection rate of CIN2 with self-sampling compared with cytology. However, no difference was seen between the arms in the detection rate of CIN3+. It thus seems that CIN is detected at an earlier stage with self-sampling than with cytology, but the impact of this needs to be further explored.

Second, as management of HPV-positive women with normal cytology results is a challenge, we wanted to evaluate the proportion of cases of histological CIN2+ in these women. In this prospective study we performed LEEP and found that 15% (6/40) of the women had undetected CIN2+. These findings can be used in counseling women about the risk of cervical cancer and helping clinicians in decisions on management.

Third, we performed a cost-effectiveness analysis on the same study population as in Study I. Self-sampling for HPV testing resulted in a higher participation rate and more detected cases of CIN2+ at a lower cost and was regarded as more cost-effective than Pap smear cytology in cervical screening. These results can guide policy-makers when planning future screening programs.

Fourth, we compared self-sampling with sampling by medical professionals for HPV testing in detection of CIN2+, using a combination of an FTA card as storage medium and a PCR-based HPV test (hpVIR) in women aged 30–60 years (n=11 951). No difference in the detection rates of histological CIN2+ was found between the arms.

Taken together, self-sampling resulted in a higher participation rate than sampling by medical professionals in cervical screening and that triage with repeated self-sampling resulted in high compliance and detection rate of CIN2+. As repeated self-sampling for HPV testing was also cost-effective, it could serve as an attractive alternative in the development of future cervical screening programs. More research is needed on how to refine the management of HPV-positive women by self-sampling only.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 81
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1641
Keywords
HPV, self-sampling, cervical screening, CIN2+, cost-effectiveness
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-405864 (URN)978-91-513-0882-1 (ISBN)
Public defence
2020-04-17, Sal IV, Universitetshuset, Biskopsgatan 3, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2020-03-27 Created: 2020-02-29 Last updated: 2020-03-27
Gustavsson, I. M., Aarnio, R., Myrnäs, M., Lindberg, J. H., Taku, O., Meiring, T., . . . Gyllensten, U. B. (2019). Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening. Virology Journal, 16(1), Article ID 107.
Open this publication in new window or tab >>Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening
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2019 (English)In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 16, no 1, article id 107Article in journal (Refereed) Published
Abstract [en]

Background

The indicating FTA card is a dry medium used for collection of cervical samples. HPVIR is a multiplex real-time PCR test that detects 12 high-risk human papillomavirus types (hrHPV) and provides single genotype information for HPV16, − 31, − 35, − 39, − 51, − 56, and − 59 and pooled type information for HPV18/45 and HPV33/52/58. The aim of this study was to evaluate whether a strategy with cervical samples collected on the FTA card and subsequently analysed with the HPVIR test complies with the criteria of the international guidelines for a clinically validated method for cervical screening.

Methods

We performed a non-inferiority test comparing the clinical sensitivity and specificity of the candidate test (FTA card and HPVIR) with a clinically validated reference test (Cobas® HPV test) based on liquid-based cytology (LBC) samples. Two clinical samples (LBC and FTA) were collected from 896 participants in population-based screening. For evaluation of the specificity we used 799 women without ≥ CIN2, and for clinical sensitivity we used 67 women with histologically confirmed ≥ CIN2. The reproducibility was studied by performing inter- and intra-laboratory tests of 558 additional clinical samples.

Results

The clinical sensitivity and specificity for samples collected on the FTA card and analysed using the HPVIR test were non-inferior to samples analysed with the Cobas® HPV test based on LBC samples (non-inferiority test score, p = 1.0 × 10− 2 and p = 1.89 × 10− 9, respectively). Adequate agreement of > 87% was seen in both the intra- and inter-laboratory comparisons.

Conclusions

Samples collected on the indicating FTA card and analysed with HPVIR test fulfil the requirements of the international guidelines and can therefore be used in primary cervical cancer screening.

Keywords
HPV, DNA testing, Primary cervical cancer screening, International guidelines
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-394268 (URN)10.1186/s12985-019-1216-7 (DOI)000483382500001 ()31438976 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Cancer Society
Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-10-09Bibliographically approved
Aarnio, R., Wikström, I., Gustavsson, I. M., Gyllensten, U. B. & Olovsson, M. (2019). Diagnostic excision of the cervix in women over 40 years with human papilloma virus persistency and normal cytology. European journal of obstetrics & gynecology and reproductive biology: X, 3, Article ID 100042.
Open this publication in new window or tab >>Diagnostic excision of the cervix in women over 40 years with human papilloma virus persistency and normal cytology
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2019 (English)In: European journal of obstetrics & gynecology and reproductive biology: X, ISSN 2590-1613, Vol. 3, article id 100042Article in journal (Refereed) Published
Abstract [en]

Objective: Persistent infection with human papillomavirus (HPV) is recognized as the main risk factor of cervical cancer. Investigation via cytology and colposcopy have lower sensitivity than HPV testing in the diagnosis of high-grade cervical intraepithelial neoplasia (CIN2+). Despite normal cytology and colposcopy findings women with persistent HPV infection have an increased risk of CIN2+. The aim of the study was to evaluate the proportion of histologically confirmed CIN2+ in women with persistent HPV infection and normal Pap smears.

Study design: From April 2013 until March 2016 we prospectively recruited 91 women over 40 years with persistent HPV infection without any abnormalities in cytology. Of these, 40 women attended a gynecological examination including an HPV test, Pap smear, endocervical cytology, colposcopy with biopsies and diagnostic loop electrosurgical excision procedure (LEEP). Biopsy and LEEP samples were subjected to histological examination.

Results: CIN2+ was verified by histological examination of the LEEP sample in 6/40 (15%) of the women. All the cytological samples were normal and none of the biopsies confirmed CIN2+. Only 19/40 women still had a persistent HPV infection at the study visit. None of the 21/40 women who had cleared their HPV infection at the study visit had CIN2+ in histology of the LEEP sample.

Conclusions: A persistent HPV infection needs to be monitored despite normal Pap smears, since 6/40 (15%) women older than 40 years, was revealed to have an undiagnosed CIN2+ when LEEP was performed. Counseling women regarding the risk of cervical cancer and the expected effect of an eventual LEEP can help them to make an optimal informed choice.

Keywords
Cervical intraepithelial neoplasia, Colposcopy, Human papillomavirus, Loop electrical excision procedure, Transformation zone
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-400770 (URN)10.1016/j.eurox.2019.100042 (DOI)31404426 (PubMedID)
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-03-18Bibliographically approved
Berggrund, M., Gustavsson, I. M., Aarnio, R., Lindberg, J. H., Sanner, K., Wikström, I., . . . Gyllensten, U. B. (2019). HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia.. Virology Journal, 16, Article ID 146.
Open this publication in new window or tab >>HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia.
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2019 (English)In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 16, article id 146Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: This study was performed to evaluate the use of high-risk HPV (hrHPV) viral load in screening tests for cervical cancer to predict persistent infection and presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).

METHODS: We followed women between 30 and 60 years of age who performed self-sampling of vaginal fluid and subsequently a hrHPV test. Women who were hrHPV positive in their screening test repeated the hrHPV test 3-6 months later and were included in the present study.

RESULTS: Our results show that women with a persistent HPV16 infection had higher HPV viral load in their primary screening test than women with transient infections (p = 5.33e-03). This was also true for sum of viral load for all hrHPV types in the primary screening test (p = 3.88e-07). 48% of women with persistent HPV16 infection and CIN2+ had an increase in HPV16 titer in the follow-up test, as compared to only 20% of women with persistent infection but without CIN2+ lesions. For the sum of all hrHPV types, 41% of women with persistent infection and CIN2+ had an increase in titer as compared to 26% of women without CIN2 + .

CONCLUSIONS: The results show that hrHPV viral load in the primary screening HPV test is associated with the presence of CIN2+ and could be used in triaging hrHPV positive women for different follow-up strategies or recall times. Serial testing of hrHPV viral load has the potential to distinguish women with CIN2+ lesions from women with persistent infection but without CIN2+ lesions.

Keywords
CIN2+, Cervical cancer, HPV viral load, Self-sampling, hrHPV
National Category
Obstetrics, Gynecology and Reproductive Medicine Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-406972 (URN)10.1186/s12985-019-1253-2 (DOI)000513831600002 ()31771594 (PubMedID)
Funder
Swedish Cancer SocietySwedish Foundation for Strategic Research Swedish Research Council
Available from: 2020-03-17 Created: 2020-03-17 Last updated: 2020-03-20Bibliographically approved
Gustavsson, I. M., Aarnio, R., Berggrund, M., Lindberg, J. H., Sanner, K., Wikström, I., . . . Gyllensten, U. B. (2019). Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.. International Journal of Cancer, 144(1), 89-97
Open this publication in new window or tab >>Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 1, p. 89-97Article in journal (Refereed) Published
Abstract [en]

We conducted a randomised study to compare vaginal self-sampling with assisted sampling by medical personnel on the cervix for HPV testing in primary screening. The first aim was to determine if the HPV prevalence is independent of sampling location (vagina versus cervix) and the person performing the sampling. The second aim was to evaluate if the two sampling strategies differed in the detection rate of CIN2+. In total, 19,523 women were randomised into two groups, with 9926 invited to perform self-sampling (SS arm) using the Rover VIBA-brush and 9597 offered assisted sampling using the cytobrush (AS arm). All samples were applied to the indicating FTA elute card and analysed for high-risk HPV using the hpVIR real-time PCR assay. The outcome for the first aim was HPV prevalence and for the second aim the number of CIN2+ based on histology. In the SS arm, 52.7% of invited women participated in the study, as compared to 34.2% in the AS arm. All samples contained sufficient amount of nuclear DNA for a valid HPV result, with vaginal samples having a higher DNA amount than cervical samples (p < 4.62 × 10-11 ). HPV prevalence was 4.6% in the SS arm and 4.1% in the AS arm (p = 5.5 × 10-2 ), and the distribution of HPV types similar between arms. There was no difference in the prevalence of CIN2+ per 1000 women screened between arms (p = 0.86). The results show that vaginal self-sampling is an equivalent alternative to sampling by medical personnel for HPV typing and identification of CIN2+.

Keywords
HPV test, cervical cancer, randomised study, screening, self-sampling
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-367086 (URN)10.1002/ijc.31637 (DOI)000451479900009 ()29943822 (PubMedID)
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Swedish Cancer Society
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2020-03-18Bibliographically approved
Gustavsson, I. M., Aarnio, R., Berggrund, M., Lindberg, J. H., Strand, A.-S., Sanner, K., . . . Gyllensten, U. B. (2018). Randomised study shows that repeated self-sampling and HPV test has more than two-fold higher detection rate of women with CIN2+ histology than Pap smear cytology. British Journal of Cancer, 118(6), 896-904
Open this publication in new window or tab >>Randomised study shows that repeated self-sampling and HPV test has more than two-fold higher detection rate of women with CIN2+ histology than Pap smear cytology
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2018 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 118, no 6, p. 896-904Article in journal (Refereed) Published
Abstract [en]

Background:

This randomised study compared the detection rate of cervical intraepithelial neoplasia-positive (CIN2+) based on histology in women performing repeated self-sampling of vaginal fluid (VF) for human papillomavirus (HPV) test with a control group following the ordinary screening by Pap smear cytology.

Methods:

36390 women aged 30–49 years scheduled for invitation to organised screening were randomised in two groups, one to perform self-sampling of VF for HPV test (n=17 997, HPV arm) and the other group to perform screening by PAP smear cytology (n=18 393, control arm). HPV positive women in the HPV arm repeated the self-sampling and the HPV test on average 4.4 months later and those with two consecutive positive HPV tests were referred to colposcopy. Outcome was CIN2+ based on histology during 18-month follow-up.

Results:

Participation rate was 47% in the HPV arm and 39% in the control arm. The HPV prevalence in the first self-sampling was 6.9%, and 71% of these women were HPV positive in their second test. For the per-protocol approach, cumulative prevalence of histological CIN2+ in the HPV arm was 20.2 per 1000 women screened as compared to 10.8 in the control arm. The cumulative prevalence of CIN2+ diagnosed per 1000 years screened was 160.8 in the HPV arm as compared with 25.4 in the control arm.

Conclusions:

Repeated self-sampling of VF and HPV test had more than a two-fold higher discovery rate of CIN2+ per 1000 women screened as compared with PAP smear cytology.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-367087 (URN)10.1038/bjc.2017.485 (DOI)000427945800030 ()29438367 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Cancer SocietySwedish Society for Medical Research (SSMF)
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2020-03-18Bibliographically approved
Olovsson, M., Aarnio, R., Rezapour, M., Segebladh, B., Sjöö, E.-L. & Wilander, E. (2013). HPV-test ersätter Pap-test i Uppsala [Letter to the editor]. Läkartidningen, 110(13-14), 695-696
Open this publication in new window or tab >>HPV-test ersätter Pap-test i Uppsala
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2013 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 13-14, p. 695-696Article in journal, Letter (Refereed) Published
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-272560 (URN)23634626 (PubMedID)
Note

[HPV test replaces Pap test in Uppsala]

Available from: 2016-01-14 Created: 2016-01-14 Last updated: 2017-11-30Bibliographically approved
Nilsson, C. G., Palva, K., Aarnio, R., Morcos, E. & Falconer, C. (2013). Seventeen years' follow-up of the tension-free vaginal tape procedure for female stress urinary incontinence. International Urogynecology Journal, 24(8), 1265-1269
Open this publication in new window or tab >>Seventeen years' follow-up of the tension-free vaginal tape procedure for female stress urinary incontinence
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2013 (English)In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 24, no 8, p. 1265-1269Article in journal (Refereed) Published
Abstract [en]

The minimally invasive tension-free vaginal tape (TVT) operation has become the "gold standard" of incontinence surgery. The aim of the present study was to evaluate the long-term effect of the tape material and to assess the continence status 17 years after surgery A cohort of 90 women operated upon with the TVT procedure at three Nordic centers has been prospectively followed for 17 years. All of the women alive according to national registries were contacted and invited to visit the clinics for evaluation. Pelvic examination was performed to reveal any adverse effects of the tape material. Objective and subjective continence status were assessed by a cough stress test and the patients' global impression of improvement as well as by condition-specific quality of life questionnaires. Seventy-eight percent of the potentially assessable women were evaluated either by a clinic visit or by a telephone interview. One case of a minimal, symptom-free tape extrusion was seen. No other tape complications occurred. Over 90 % of the women were objectively continent. Eighty-seven per cent were subjectively cured or significantly improved. The TVT operation is durable for 17 years, with a high satisfaction rate and no serious long-term tape-induced adverse effects.

Keywords
Tension-free vaginal tape, Stress urinary incontinence, Long term follow-up
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-207023 (URN)10.1007/s00192-013-2090-2 (DOI)000322135700005 ()
Available from: 2013-09-10 Created: 2013-09-09 Last updated: 2017-12-06Bibliographically approved
Aarnio, R., Isacson, I., Sanner, K., Gustavsson, I. M., Gyllensten, U. B. & Olovsson, M.Comparison of vaginal self-sampling and cervical sampling by medical professionals for the detection of HPV and CIN2+: a randomized study.
Open this publication in new window or tab >>Comparison of vaginal self-sampling and cervical sampling by medical professionals for the detection of HPV and CIN2+: a randomized study
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Primary screening with human papillomavirus (HPV) test is more effective in reducing cervical cancer incidence than cytology and it also offers the opportunity to self-sample. We conducted a randomized study to compare vaginal self-sampling with cervical sampling by medical professionals for HPV testing concerning prevalence of HPV and detection of cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+)  or grade 3 or worse (CIN3+) in primary screening. In total, 11 951 women aged 30–60 years were randomized into two groups, 5961 for self-sampling (SS arm) and 5990 for sampling by medical professionals (SMP arm). Sampling was performed with a Rovers®Viba-brush in the SS arm and a cytobrush in the SMP arm. All samples were applied to an indicating FTA elute card and analyzed for HPV using a clinically validated real-time PCR test (hpVIR). All HPV-positive women performed repeated sampling about six months later using the same procedure as used initially. All HPV-positive women in the second sampling were referred to colposcopy. HPV prevalence in the first test did not differ between the SS arm (6.8%, 167/2466) and the SMP arm (7.8%, 118/1519) (p=0.255). The prevalence of CIN2+ per 1000 screened women was 17 (43/2466 × 1000) (95%CI 13–24) in the SS arm and 21 (32/1519 × 1000) (95%CI 15–30) in the SMP arm. For CIN3+, the prevalence per 1000 screened women was 14 (35/2466 × 1000) (95%CI 10–20) in the SS arm and 15 (23/1519 × 1000) (95%CI 10–23) in the SMP arm.  In conclusion, self-sampling and sampling by medical professionals showed the same prevalence of HPV and detection rate of CIN2+ and CIN3+ in histology.

Novelty and Impact

Offering self-sampling in primary cervical screening results in similar rates of HPV prevalence and detection of CIN2+ and CIN3+ compared with sampling by medical professionals when using an FTA card as storage medium and PCR-based HPV test (hpVIR). Considering health-economic aspects, resources should be directed towards self-sampling as a first choice for primary cervical screening, with careful follow-up of this strategy.

Keywords
Self-sampling, HPV test, Primary cervical screening
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-405547 (URN)
Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2020-03-12Bibliographically approved
Aarnio, R., Östensson, E., Olovsson, M., Gustavsson, I. M. & Gyllensten, U. B.Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study.
Open this publication in new window or tab >>Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background

Human papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening.

Methods

A cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36 390 women aged 30–49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17 997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18 393, Pap smear arm).

Results

Self-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 228 642 vs. € 781 139). 

Conclusions

This study projected that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening.

 

Keywords
Self-sampling, HPV testing, primary cervical screening, cost-effectiveness, CIN2+, precancerous lesion, cervical cancer
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-405549 (URN)
Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2020-03-12Bibliographically approved
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