| 1. |
- 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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| 2. |
- Aarnio, Riina, 1971-, et al.
(författare)
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Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study
- 2020
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 20:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundHuman 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.MethodsA 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).ResultsSelf-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). ConclusionsThis 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.
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| 3. |
- Aarnio, Riina
(författare)
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Self-sampling for HPV testing in primary cervical screening : Including clinical and health economic aspects
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 4. |
- Berggrund, Malin, 1989-
(författare)
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Identification and clinical implementation of biomarkers for cervical cancer
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction of organised screening programs and prophylactic vaccination against human papilloma virus (HPV) have successfully reduced the incidence of cervical cancer globally. In Sweden, the incidence has been reduced by about 50 % since the introduction of the national screening programme in the late 1960’s. Despite these efforts, cervical cancer is still a major cause of cancer deaths globally.In order to reduce cervical cancer, the screening program should have a high participation rate and be based on a sensitive and specific screening test. About 20 % of women in Sweden do not participate in the organised screening program, and during the last years we have also seen a rise in cervical cancer cases in Sweden among women who participate in the screening program. Thus, there is a need to develop improved screening strategies that result in a higher participation rate, and are based on tests that more precisely identify women with high risk of developing cervical cancer. This includes searching for novel biological markers (biomarkers) that can be used to more accurately identify women with a high risk of developing cervical cancer.By offering women self-sampling for HPV analysis through direct mailing of sample kits with a chemically treated paper card, the FTA card, we were able to increase the participation rate in the screening program. We also found that the use of repeated self-sampling for women that were HPV positive in the primary screening sample increased the number of women detected with higher risk of cervical cancer (Paper II). Self-sampling was shown to be non-inferior to assisted sampling by midwife (Paper III). Using this sample collection device, we further investigated the association between increased risk of cervical cancer and HPV viral load (Paper V) as well as the vaginal microbiota (Paper VI). We also showed that proteins in the vaginal fluid can be studied using self-sampling and the FTA card (Paper I). Lastly, we identified plasma proteins that are associated with cervical cancer and could represent future biomarkers (Paper IV).This thesis has provided novel aspects on the present screening strategy, explored opportunities to increase the participation rate as well as examined possible future biomarkers for screening of cervical cancer.
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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. |
- Bergman-Larsson, Julia, et al.
(författare)
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Combined expression of HOXA11 and CD10 identifies endometriosis versus normal tissue and tumors
- 2022
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Ingår i: Annals of Diagnostic Pathology. - : Elsevier. - 1092-9134 .- 1532-8198. ; 56
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Tidskriftsartikel (refereegranskat)abstract
- The gold standard for diagnosing endometriosis is by laparoscopic visual demonstration of ectopic endometrial lesions outside the uterus, preferably verified by biopsy and microscopical examination. Molecular markers to facilitate the microscopical diagnosis of endometriosis and for distinguishing endometriosis from other benign and malignant lesions are lacking. Our aim was to test and validate an immunohistochemical antibody panel for improved diagnostic accuracy of endometriosis. Both CD10 and HOXA11 have been implicated in regulation of endometrial homeostasis. Here we have analyzed the expression pattern of these two proteins using immunohistochemistry on human tissues in a tissue microarray format. CD10 and HOXA11 expression in endometriosis lesions were compared to expression patterns in a range of normal tissues and in primary- and metastatic lesions of endometrial-, cervical- and ovarian cancer. HOXA11 and CD10 were expressed in 98% and 91% of endometriosis lesions and the combined double-positive expression profile of both HOXA11 and CD10 was highly sensitive for ectopic endometrial tissue (90%). The specificity and sensitivity for this double-positive signature in endometriosis was significantly different from all investigated tissues, cancers and metastases except normal, eutopic endometrial- and cervical mucosa. The combination of HOXA11 and CD10 expression profiles provides a useful tool to identify ectopic endometrial tissue and for distinguishing endometriosis from various types of gynecological malignancies and metastases.
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| 7. |
- Bjorvang, Richelle D., et al.
(författare)
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Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies
- 2022
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 208
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs) are industrial chemicals resistant to degradation and have been shown to have adverse effects on reproductive health in wildlife and humans. Although regulations have reduced their levels, they are still ubiquitously present and pose a global concern. Here, we studied a cohort of 185 women aged 21-43 years with a median of 2 years of infertility who were seeking assisted reproductive technology (ART) treatment at the Carl von Linne Clinic in Uppsala, Sweden. We analyzed the levels of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenyl ethers (PBDEs), and 8 perfluoroalkyl substances (PFASs) in the blood and follicular fluid (FF) samples collected during ovum pick-up. Impact of age on chemical transfer from blood to FF was analyzed. Associations of chemicals, both individually and as a mixture, to 10 ART endpoints were investigated using linear, logistic, and weighted quantile sum regression, adjusted for age, body mass index, parity, fatty fish intake and cause of infertility. Out of the 30 chemicals, 20 were detected in more than half of the blood samples and 15 in FF. Chemical transfer from blood to FF increased with age. Chemical groups in blood crossed the blood-follicle barrier at different rates: OCPs > PCBs > PFASs. Hexachlorobenzene, an OCP, was associated with lower anti-Miillerian hormone, clinical pregnancy, and live birth. PCBs and PFASs were associated with higher antral follicle count and ovarian response as measured by ovarian sensitivity index, but also with lower embryo quality. As a mixture, similar findings were seen for the sum of PCBs and PFASs. Our results suggest that age plays a role in the chemical transfer from blood to FF and that exposure to POPs significantly associates with ART outcomes. We strongly encourage further studies to elucidate the underlying mechanisms of reproductive effects of POPs in humans.
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| 8. |
- Cheng, Liqin, et al.
(författare)
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A MicroRNA Gene Panel Predicts the Vaginal Microbiota Composition
- 2021
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Ingår i: mSystems. - : American Society for Microbiology. - 2379-5077. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- The vaginal microbiota plays an essential role in vaginal health. The vaginas of many reproductive-age women are dominated by one of the Lactobacillus species. However, the vaginas of a large number of women are characterized by the colonization of several other anaerobes. Notably, some women with the non-Lactobacillus-dominated vaginal microbiota develop bacterial vaginosis, which has been correlated with sexually transmitted infections and other adverse outcomes. However, interactions and mechanisms linking the vaginal microbiota to host response are still under investigation. There are studies suggesting a link between human microRNAs and gut microbiota, but limited analysis has been carried out on the interplay of microRNAs and vaginal microbiota. In this study, we performed a microRNA expression array profiling on 67 vaginal samples from young Swedish women. MicroRNAs were clustered into distinct groups according to vaginal microbiota composition. Interestingly, 182 microRNAs were significantly elevated in their expression in the non-Lactobacillus-dominated community, suggesting an antagonistic relationship between Lactobacillus and microRNAs. Of the elevated microRNAs, 10 microRNAs displayed excellent diagnostic potential, visualized by receiver operating characteristics analysis. We further validated our findings in 34 independent samples where expression of top microRNA candidates strongly separated the Lactobacillus-dominated community from the non-Lactobacillus-dominated community in the vaginal microbiota. Notably, the Lactobacillus crispatus-dominated community showed the most profound differential microRNA expression compared with the non-Lactobacillus-dominated community. In conclusion, we demonstrate a strong relationship between the vaginal microbiota and numerous genital microRNAs, which may facilitate a deeper mechanistic interplay in this biological niche. IMPORTANCE Vaginal microbiota is correlated with women's health, where a non-Lactobacillus-dominated community predisposes women to a higher risk of disease, including human papillomavirus (HPV). However, the molecular relationship between the vaginal microbiota and host is largely unexplored. In this study, we investigated a link between the vaginal microbiota and host microRNAs in a group of young women. We uncovered an inverse correlation of the expression of microRNAs with the abundance of Lactobacillus species in the vaginal microbiota. Particularly, the expression of microRNA miR-23a-3p and miR-130a-3p, displaying significantly elevated levels in non-Lactobacillus-dominated communities, predicted the bacterial composition of the vaginal microbiota in an independent validation group. Since targeting of microRNAs is explored in the clinical setting, our results warrant investigation of whether microRNA modulation could be used for treating vaginosis recurrence and vaginosis-related diseases. Conversely, commensal bacteria could be used for treating diseases with microRNA aberrations.
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| 9. |
- Cheng, Liqin, et al.
(författare)
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Vaginal microbiota and human papillomavirus infection among young Swedish women
- 2020
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Ingår i: npj Biofilms and Microbiomes. - : Springer Science and Business Media LLC. - 2055-5008. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. To define the HPV-associated microbial community among a high vaccination coverage population, we carried out a cross-sectional study with 345 young Swedish women. The microbial composition and its association with HPV infection, including 27 HPV types, were analyzed. Microbial alpha-diversity was found significantly higher in the HPV-infected group (especially with oncogenic HPV types and multiple HPV types), compared with the HPV negative group. The vaginal microbiota among HPV-infected women was characterized by a larger number of bacterial vaginosis-associated bacteria (BVAB), Sneathia, Prevotella, and Megasphaera. In addition, the correlation analysis demonstrated that twice as many women with non-Lactobacillus-dominant vaginal microbiota were infected with oncogenic HPV types, compared with L. crispatus-dominated vaginal microbiota. The data suggest that HPV infection, especially oncogenic HPV types, is strongly associated with a non-Lactobacillus-dominant vaginal microbiota, regardless of age and vaccination status.
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| 10. |
- Grundström, Hanna, 1982-, et al.
(författare)
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Cross-cultural adaptation of the Swedish version of Endometriosis Health Profile-30
- 2020
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Ingår i: Journal of Obstetrics and Gynaecology. - : Informa UK Limited. - 0144-3615 .- 1364-6893. ; 40:7, s. 969-973
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Tidskriftsartikel (refereegranskat)abstract
- The Endometriosis Health Profile-30 (EHP-30) is focusing on the effect of endometriosis symptoms upon health-related quality of life. The aim of this study was to pre-test and culturally adapt the Swedish version of EHP-30. Eighteen Swedish-speaking women with laparoscopically verified diagnosis of endometriosis answered the questionnaire and 17 were interviewed regarding their interpretations of the questionnaire. Demographics, distribution of answers, roof-ceiling effects and missing answers were analysed. The interviews were analysed using the qualitative approach proposed by Beaton et al. The Swedish version of EHP-30 was experienced as accessible with 100% data completeness and a roof effect (11%) in one dimension. Some women had difficulties with the instructions and one word should be replaced in order to culturally adapt the questionnaire. In conclusion, the Swedish version of EHP-30 is a useful and well-accepted questionnaire for women with endometriosis in Sweden, but a minor change of wording is recommended.Impact statement What is already known on this subject? Cross-cultural adaptation and psychometric testing are crucial when introducing translated questionnaires. Cross-cultural adaptation is a process that looks at both translational and cultural issues when a questionnaire is being prepared for use in another country than the original. EHP-30 has been translated into Swedish but has not yet been cross-culturally adapted. What do the results of this study add? The Swedish version of EHP-30 was experienced as a useful and well-accepted questionnaire for women with endometriosis, but a minor change of wording is recommended in one question to make the questionnaire convergent with the original version.
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