| 1. |
- Orgeas, C, et al.
(författare)
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Breast cancer incidence after hormonal infertility treatment in Sweden: a cohort study
- 2009
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Ingår i: Am J Obstet Gynecol. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 200:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the impact of infertility treatment with causes of infertility on incidence of breast cancer. STUDY DESIGN: Historical prospective cohort study of 1135 women attending major university clinics for treatment of infertility in Sweden, 1961-1976. Women were classified as users of clomiphene citrate or gonadotropins, or a combination of both therapies. Standardized incidence ratios were calculated to estimate relative risk of breast cancer. RESULTS: We observed 54 cases of breast cancer during 1961-2004, which did not significantly exceed those expected. Users of high-dose clomiphene citrate had an almost 2-fold increased risk (standardized incidence ratio, 1.90; 95% confidence interval, 1.08-3.35). This association was more pronounced among women referred for nonovulatory factors, with 3-fold increased risk (standardized incidence ratio, 3.00; 95% confidence interval, 1.35-6.67). CONCLUSION: No overall increased risk for breast cancer was shown with infertility treatment. Women with nonovulatory causes treated with high-dose clomiphene citrate therapy may have an elevated risk for breast cancer.
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| 2. |
- Sanner, Karin, 1961-, et al.
(författare)
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Ovarian epithelial neoplasia after hormonal infertility treatment: long-term follow-up of a historical cohort in Sweden
- 2009
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Ingår i: Fertil Steril. - : Elsevier BV. ; 91:4, s. 1152-1158
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the association between hormonal infertility treatment and ovarian neoplasia. DESIGN: Historical cohort study. SETTING: Three university hospitals in Sweden. PATIENT(S): A total of 2,768 women assessed and treated for infertility and infertility-associated disorders between 1961 and 1975. INTERVENTION(S): Exposed women received clomiphene citrate and/or gonadotropins. MAIN OUTCOME MEASURE(S): Incidence of ovarian neoplasia. RESULT(S): No overall excess risk of invasive ovarian cancer emerged compared with the general population. In women with gonadotropin treatment for non-ovulatory disorders, the risk was elevated (standardized incidence ratio [SIR] = 5.89; 95% confidence interval [CI] 1.91-13.75); four of the five cases reported hCG treatment only, rendering the biological plausibility uncertain. Multivariate analysis within the cohort indicated that treatment with gonadotropins only was associated with an increased risk of invasive cancer (relative risk = 5.28; 95% CI 1.70-16.47). For borderline tumors, a more than threefold overall increase of tumors (SIR = 3.61; 95% CI 1.45-7.44) was noted; women exposed to clomiphene because of ovulatory disorders showed the highest risk (SIR = 7.47; 95% CI 1.54-21.83). CONCLUSION(S): Our findings of increased risk of ovarian cancer after gonadotropins and of borderline tumors after clomiphene treatment need to be interpreted with caution. However, concern is raised, and further research on the long-term safety particularly of modern hormonal infertility treatment in IVF programs is warranted.
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| 3. |
- Aarnio, Riina, 1971-, et al.
(författare)
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Comparison of vaginal self-sampling and cervical sampling by medical professionals for the detection of HPV and CIN2+ : a randomized study
- 2021
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 148:12, s. 3051-3059
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Tidskriftsartikel (refereegranskat)abstract
- 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 RoversViba-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 6 months later using the same procedure as used initially. All HPV-positive women in the second sampling were referred to colposcopy. The prevalence of HPV in the first test did not differ between the SS arm (6.8%, 167/2466) and the SMP arm (7.8%, 118/1519) (P = .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.
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| 4. |
- Berggrund, Malin, et al.
(författare)
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HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia.
- 2019
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Ingår i: Virology Journal. - : Springer Science and Business Media LLC. - 1743-422X. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Berggrund, Malin, et al.
(författare)
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Temporal changes in the vaginal microbiota in self-samples and its association with persistent HPV16 infection and CIN2
- 2020
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Ingår i: Virology Journal. - : Springer Science and Business Media LLC. - 1743-422X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables.MethodsIn total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S™ Metagenomics Kit and Ion 16S™ metagenomics module within the Ion Reporter™ software.ResultsK-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036).ConclusionsThe vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.
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| 6. |
- Gustavsson, Inger M., et al.
(författare)
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Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.
- 2019
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 144:1, s. 89-97
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Tidskriftsartikel (refereegranskat)abstract
- 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+.
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| 7. |
- Gustavsson, Inger M., et al.
(författare)
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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
- 2018
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 118:6, s. 896-904
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Gustavsson, Inger, 1965-, et al.
(författare)
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Type-specific detection of high-risk human papillomavirus (HPV) in self-sampled cervicovaginal cells applied to FTA elute cartridge
- 2011
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 51:4, s. 255-258
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMost 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.ObjectivesTo 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 designA 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.ResultAll 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.ConclusionThe Viba-brush and the FTA cartridge are suitable for self-sampling of vaginal cells and subsequent HR-HPV typing.
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| 9. |
- Gyllensten, Ulf, et al.
(författare)
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Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer
- 2011
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 105:5, s. 694-697
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Lindell, Monica, et al.
(författare)
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Self-sampling of vaginal fluid and high-risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening
- 2012
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Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 119:2, s. 245-248
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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