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Wilander, Erik
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Publications (10 of 35) Show all publications
Sanner, K., Wikström, I., Gustavsson, I., Wilander, E., Lindberg, J. H., Gyllensten, U. & Olovsson, M. (2015). Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing.. Journal of Clinical Virology, 73, 1-7
Open this publication in new window or tab >>Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing.
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2015 (English)In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 73, p. 1-7Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Self-sampling for HPV as part of primary screening is a well-tolerated method for women not attending organized Pap smear screening and could increase coverage of cervical cancer screening.

OBJECTIVE: To investigate if the prevalence of HR-HPV varies from day to day in infected women and if one single sample is reliable for detecting an ongoing infection.

STUDY DESIGN: This is a prospective cohort study on 12 premenopausal and 13 postmenopausal women performing daily self-sampling for HR-HPV testing. They were all HR-HPV-positive 1-3 months ago. Postmenopausal women were sampled for 28 days and premenopausal women sampled during bleeding-free days in one menstrual cycle. A possible difference in viral load between the estrogen-dominated proliferative phase and the progesterone-dominated secretory phase was analyzed.

RESULTS AND CONCLUSIONS: Consistent results throughout the sampling period were observed for 19 women, with either a daily presence of HPV (14 women) or no HPV at all during the sampling period (5 women). Of 607 samples from 25 women, 596 were consistently positive or negative for HPV during the sampling period and 11 were inconsistent (2%). There was no difference in HPV copy number between the estrogen dominated proliferative or progesterone dominated secretory menstrual cycle phases. The major finding was a high degree of consistency concerning HR-HPV positivity and negativity of HR-HPV in vaginal fluid during a sustained period of daily self-sampling. It does not appear to matter whether the sample is collected in the proliferative or secretory phase.

Keywords
Cervical cancer; Human papilloma virus (HPV); Self-sampling; Repeated sampling; Screening
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-272544 (URN)10.1016/j.jcv.2015.09.016 (DOI)000367390700001 ()26498105 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2016-01-14 Created: 2016-01-14 Last updated: 2017-11-30Bibliographically approved
Hellman, K., Lindquist, D., Ranhem, C., Wilander, E. & Andersson, S. (2014). Human papillomavirus, p16(INK4A), and Ki-67 in relation to clinicopathological variables and survival in primary carcinoma of the vagina. British Journal of Cancer, 110(6), 1561-1570
Open this publication in new window or tab >>Human papillomavirus, p16(INK4A), and Ki-67 in relation to clinicopathological variables and survival in primary carcinoma of the vagina
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2014 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 110, no 6, p. 1561-1570Article in journal (Refereed) Published
Abstract [en]

Background: This study aimed to determine human papillomavirus (HPV) status and to investigate p16(INK4A) and Ki-67 expression and their correlation with clinical parameters and survival in women with primary carcinoma of the vagina (PCV). Methods: The presence of HPV DNA was evaluated by PCR. Genotyping was performed by Luminex in 68 short-term (<= 2 years) and long-term (>= 8 years) PCV survivors. p16(INK4A) and Ki-67 expression was evaluated by immunohistochemistry. Results: Human papillomavirus DNA was detected in 43% of patients, the majority (63%) of whom were HPV16 positive. High p16INK4A expression was significantly correlated with low histopathological grade (P =0.004), HPV positivity (P =0.032), and long-term survival (P =0.045). High Ki-67 expression was negatively correlated with histopathological grade (P < 0.001) and tumour size (P =0.047). There was an association between HPV positivity and low histopathological grade, but not between HPV positivity and survival. Conclusion: High p16(INK4A) expression was associated with long-term survival, but the only independent predictors for survival were tumour size and histopathological grade. Our results indicate that p16(INK4A) and Ki-67 expression might be useful in tumour grading, and that it might be possible to use p16(INK4A) expression as a marker for HPV positivity, but this has to be further elucidated.

Keywords
vaginal cancer, prognosis, HPV, p16, Ki-67
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-224465 (URN)10.1038/bjc.2014.32 (DOI)000333195800020 ()
Available from: 2014-05-15 Created: 2014-05-13 Last updated: 2017-12-05Bibliographically approved
Andersson, S., Mints, M., Gyllensten, U., Lindell, M., Gustavsson, I., Lambe, M. & Wilander, E. (2014). Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females: A retrospective database study. Oncology Letters, 8(4), 1528-1532
Open this publication in new window or tab >>Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females: A retrospective database study
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2014 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 8, no 4, p. 1528-1532Article in journal (Refereed) Published
Abstract [en]

Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18145 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females.

Keywords
cervix, carcinoma in situ, human papillomavirus 16, prevalence, old age
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-235626 (URN)10.3892/ol.2014.2347 (DOI)000342725400023 ()
Available from: 2014-11-11 Created: 2014-11-06 Last updated: 2017-12-05Bibliographically 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
Ostensson, E., Hellstrom, A.-C., Hellman, K., Gustavsson, I., Gyllensten, U., Wilander, E., . . . Andersson, S. (2013). Projected cost-effectiveness of repeat high-risk human papillomavirus testing using self-collected vaginal samples in the Swedish cervical cancer screening program. Acta Obstetricia et Gynecologica Scandinavica, 92(7), 830-840
Open this publication in new window or tab >>Projected cost-effectiveness of repeat high-risk human papillomavirus testing using self-collected vaginal samples in the Swedish cervical cancer screening program
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2013 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 7, p. 830-840Article in journal (Refereed) Published
Abstract [en]

Background Human papillomavirus (HPV) testing is not currently used in primary cervical cancer screening in Sweden, and corresponding cost-effectiveness is unclear. Objective From a societal perspective, to evaluate the cost-effectiveness of high-risk (HR)-HPV testing using self-collected vaginal samples. Design A cost-effectiveness analysis. Setting The Swedish organized cervical cancer screening program. Methods We constructed a model to simulate the natural history of cervical cancer using Swedish data on cervical cancer risk. For the base-case analysis we evaluated two screening strategies with different screening intervals: (i) cytology screening throughout the woman's lifetime (i.e. conventional cytology strategy) and (ii) conventional cytology screening until age 35years, followed by HR-HPV testing using self-collected vaginal samples in women aged 35years (i.e. combination strategy). Sensitivity analyses were performed, varying model parameters over a significant range of values to identify cost-effective screening strategies. Main outcome measures Average lifetime cost, discounted and undiscounted life-years gained, reduction in cervical cancer risk, incremental cost-effectiveness ratios with and without the cost of added life-years. Results Depending on screening interval, the incremental cost-effectiveness ratios for the combination strategy ranged from Euro43000 to Euro180000 per life-years gained without the cost of added life-years, and from Euro74000 to Euro206000 with costs of added life-years included. Conclusion The combination strategy with a 5-year screening interval is potentially cost-effective compared with no screening, and with current screening practice when using a threshold value of Euro80000 per life-years gained.

Keywords
Cervical cancer, cost-effectiveness, human papillomavirus (HPV), screening, self-sampling
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-204091 (URN)10.1111/aogs.12143 (DOI)000320549400014 ()
Available from: 2013-07-23 Created: 2013-07-22 Last updated: 2017-12-06Bibliographically approved
Andersson, S., Mints, M. & Wilander, E. (2013). Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma in situ. Oncology Letters, 6(1), 215-219
Open this publication in new window or tab >>Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma in situ
2013 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 6, no 1, p. 215-219Article in journal (Refereed) Published
Abstract [en]

The incidence rates of cervical adenocarcinoma have been increasing over the last two decades, contrary to those of squamous cell carcinoma. This trend is particularly evident among females aged <40 years and has occurred despite extensive cytology-based screening programs. The aim of the present retrospective database study was to investigate adenocarcinoma in situ (AIS) with respect to previous cytological results, high-risk (HR) human papillomavirus (HPV) infections and histological results from AIS-adjacent squamous mucosa. Databases were used to identify 32 female patients with AIS treated for various conditions between 2009 and 2012 at the Department of Gynecology, Uppsala University Hospital (Uppsala, Sweden) and previous cytological, HPV and histological results. Of the individuals in the study, 64.3% had a previously recorded cytological result showing squamous cell abnormalities; five had glandular cell abnormalities (18%) and two had AIS (7.1%). Among the patients with available HPV results, 95% were HR-HPV-positive; HPV18/45 predominated (77%), followed by HPV16 (27%). The patients with multiple HPV infections were aged <= 32 years, while patients aged >= 38 years were only infected with HPV18/45. All but three patients had cervical intraepithelial neoplasia (CIN) in the AIS-adjacent squamous mucosa, 79% of which was CIN2 or worse. The present retrospective database study suggests that AIS is detected at screening mainly due to simultaneous squamous precursor lesions and that HPV18/45 infection is an increasing co-factor for AIS in older patients. HPV analyses of glandular precursor lesions aid in the identification of female individuals at risk of progression to invasive disease, and thus have a favorable effect on adenocarcinoma prevention, together with vaccination.

Keywords
cervix, adenocarcinoma in situ, HPV, screening, Pap smear, CIN
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-206463 (URN)10.3892/ol.2013.1350 (DOI)000321079100040 ()
Available from: 2013-09-01 Created: 2013-08-30 Last updated: 2017-12-06Bibliographically approved
Gyllensten, U., Gustavsson, I., Lindell, M. & Wilander, E. (2012). Primary high-risk HPV screening for cervical cancer in post-menopausal women. Gynecologic Oncology, 125(2), 343-345
Open this publication in new window or tab >>Primary high-risk HPV screening for cervical cancer in post-menopausal women
2012 (English)In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 125, no 2, p. 343-345Article in journal (Refereed) Published
Abstract [en]

Objective. The present study was conducted to examine the value of screening for high-risk HPV in post-menopausal women.

Methods. A cohort of post-menopausal women (n =2113), age range 55-76 years, from Uppsala County, Sweden, were offered testing for both high-risk HPV and a Pap smear in the gynaecological screening during 2008-2010. For the HPV test the cervical smear sample was applied to a filter paper matrix, an indicating FTA elute card and HPV typing performed using a real-time PCR assay. Histological verified CIN2+ lesion was used as an end-point measurement.

Results. High-risk HPV were found in 6.2% (95% CI 5.2-7.3%) of the women (n = 130) and 22% (95% CI 14-32%) (n = 17) of these had CIN2 + lesions based on histology. The Pap smear taken in conjunction with the HPV test was abnormal in 9.7% (95% CI 5.7-16.3%) (n = 12) of HPV positive women. Among HPV positive women with an abnormal Pap smear, the frequency of histology verified CIN2+ lesions was 67% (95% Cl 38-86%) (n = 8), as compared to 14% (95% CI 7-24%) (n = 9) in HPV positive women with a normal smear. The prevalence of HPV16 in CIN2+ lesions (29%, 95% CI 22-37%) in post-menopausal women was less than half of previous estimates in pre-menopausal women from this population.

Conclusions. Most histological CIN2+ lesions in post-menopausal women are not recognized by a single Pap smear. A large fraction of pre-invasive cervical cancer cases in post-menopausal women result from infections by HPV types not included in the present vaccine formulas.

Keywords
Cervix, Screening, Post-menopausal, High-risk HPV, CIN
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-174701 (URN)10.1016/j.ygyno.2012.01.036 (DOI)000303227500013 ()
Available from: 2012-05-28 Created: 2012-05-25 Last updated: 2017-12-07Bibliographically approved
Lindell, M., Sanner, K., Wikström, I. & Wilander, E. (2012). Self-sampling of vaginal fluid and high-risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening. British Journal of Obstetrics and Gynecology, 119(2), 245-248
Open this publication in new window or tab >>Self-sampling of vaginal fluid and high-risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening
2012 (English)In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 119, no 2, p. 245-248Article in journal (Refereed) Published
Abstract [en]

Please cite this paper as: Lindell M, Sanner K, Wikström I, Wilander E. Self-sampling of vaginal fluid and high-risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening. BJOG 2012;119:245-248.

Objectives 

To study the value of self-sampling of vaginal fluid at home in combination with high-risk human papillomavirus (HPV) testing in a cohort of older women not attending Papanicolaou (Pap) smear screening.

Design 

Women (n = 3618), aged 50-65 years, who had not attended screening for at least 6 years were offered self-sampling of vaginal fluid at home (study cohort). The collected material was analysed for the presence of high-risk HPV (using Hybrid capture 2; Hc2). Women with a positive HPV test were referred for colposcopy. These results were compared with the results of Pap smear screening in a corresponding age group of women (controls). The end point of the study was identification of a histological cervical intraepithelial neoplasia stage 2 (CIN2) and above (CIN2+).

Results 

In all, 39.4% (n = 1426) women participated and 4.6% (n = 66) were high-risk HPV positive. Of the HPV-positive women 56 chose to attend a surgery (84.8%) after a mean time of 2.1 months and ten of these women (17.9%) showed CIN2+, corresponding to 0.70% of all participating women. In the controls, who participated in organised Pap smear screening, the prevalence of CIN2+ was 0.25% (15/6048). The odds ratio for identification of CIN2+ in women aged 50 years or older performing self-sampling and HPV test in comparison with Pap smear was: 2.84 (95% CI 1.14-6.77, P = 0.0174). In older women primary high-risk HPV testing (Hc2) and Pap smear screening showed equal specificity of around 96%.

Conclusions

Self-sampling of vaginal fluid in combination with high-risk HPV testing appears to be an attractive method to improve screening coverage and decrease the prevalence of cervical cancer in women aged 50 years or older.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-164777 (URN)10.1111/j.1471-0528.2011.03147.x (DOI)000298016600016 ()22017806 (PubMedID)
Available from: 2011-12-27 Created: 2011-12-27 Last updated: 2017-12-08Bibliographically approved
Gyllensten, U., Sanner, K., Gustavsson, I., Lindell, M., Wikström, I. & Wilander, E. (2011). Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer. British Journal of Cancer, 105(5), 694-697
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, p. 694-697Article 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.

Keywords
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
Gustavsson, I., Juko-Pecirep, I., Backlund, I., Wilander, E. & Gyllensten, U. (2009). Comparison between the Hybrid Capture 2 and the hpVIR real-time PCR for detection of human papillomavirus in women with ASCUS or low grade dysplasia. Journal of Clinical Virology, 45(2), 85-89
Open this publication in new window or tab >>Comparison between the Hybrid Capture 2 and the hpVIR real-time PCR for detection of human papillomavirus in women with ASCUS or low grade dysplasia
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2009 (English)In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 45, no 2, p. 85-89Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Human papillomavirus (HPV) testing is an important part of cervical carcinoma screening, and the most widely used assay for detection of HPV is Hybrid Capture 2 (HC2). OBJECTIVES: We compare the HC2 with the real-time PCR hpVIR assay for detection of HPV in follow-up smears of 398 women diagnosed with atypical squamous cells of unknown significance (ASCUS) or low grade cervical intraepithelial neoplasia (CIN 1) in their initial smear. STUDY DESIGN: The two assays target the same set of high-risk (HR) HPVs with exception of HPV68. hpVIR identify individual or groups of HPV types as well as their viral load, while HC2 identify HR HPVs without specification of type. RESULTS: 34% (131/391) of the women were positive with HC2 and 45% (175/391) with hpVIR. 16% (63/391) were positive only with hpVIR and among those with cytology available 6% (3/52) had a CIN 2. The 3% (13/391) of women positive only with HC2 either contained low-risk HPVs or copy numbers below the cut-off for the hpVIR assay. CONCLUSION: The hpVIR assay has a similar sensitivity and specificity as HC2, but hpVIR detect a higher frequency of high-risk HPV infections.

Keywords
Cervical carcinoma, Human papillomavirus, Real-time PCR
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-107331 (URN)10.1016/j.jcv.2009.04.012 (DOI)000267388700001 ()19451022 (PubMedID)
Available from: 2009-08-06 Created: 2009-08-06 Last updated: 2017-12-13Bibliographically approved
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