HPV self-sampling in organized cervical cancer screening program: A randomized pilot study in Estonia in 2021.

BACKGROUND: Cervical cancer incidence in Estonia ranks among the highest in Europe, but screening attendance has remained low. This randomized study aimed to evaluate the impact of opt-in and opt-out human papillomavirus (HPV) self-sampling options on participation in organized screening. METHODS: A random sample of 25,591 women were drawn from the cervical cancer screening target population who were due to receive a reminder in autumn 2021 and thereafter randomly allocated to two equally sized intervention arms (opt-out and opt-in) receiving a choice between HPV self-sampling or clinician sampling. In the opt-out arm, a self-sampler was sent to home address by regular mail; the opt-in arm received an e-mail containing a link to order a self-sampler online. The remaining 30,102 women in the control group received a standard reminder for conventional screening. Participation by intervention arm, age and region of residence was calculated; a questionnaire was used to assess self-sampling user experience. RESULTS: A significant difference in participation was seen between opt-out (41.7%) (19.8% chose self-sampling and 21.9% clinician sampling), opt-in (34.1%) (7.9% self-sampling, 26.2% clinician sampling) and control group (29.0%, clinician sampling only). All age groups and regions in the intervention arms showed higher participation compared to the control group, but the size of the effect varied. Among self-sampling users, 99% agreed that the device was easy to use and only 3.5% preferred future testing at the clinic. CONCLUSION: Providing women with a choice between self-sampling and clinician sampling significantly increased participation in cervical cancer screening. Opt-in and opt-out options had a different effect across age groups, suggesting the need to adapt strategies.

Human papillomavirus self-sampling for long-term non-attenders in cervical cancer screening: A randomised feasibility study in Estonia.

OBJECTIVE: Organised cervical cancer screening was started in Estonia in 2006, but participation is still low. Human papillomavirus (HPV) self-sampling has proved to increase screening uptake. This study addressed the feasibility of HPV self-sampling and the acceptance of this method among long-term screening non-attenders. METHODS: A randomised intervention study was conducted in Estonia in 2020. Women born in 1958-1983 without a Pap smear in 2013-2019 were identified in the Estonian Health Insurance Fund database. From them, 12,000 women were randomly allocated to three equal-sized study groups. The opt-out group received a questionnaire and a Qvintip® sampling device by regular mail. Two opt-in groups received a questionnaire and an e-mail invitation to order a self-sampler online; one received Qvintip and the other Evalyn® Brush. Participants background characteristics were obtained from the Population Register. The effect of covariates on participation rate was estimated with multivariate Poisson regression. Acceptance of self-sampling was analysed according to agreement with statements in the questionnaire. RESULTS: The overall participation rate was 16% with significant differences between opt-out (26%) and opt-in (11%) groups. Compared to the opt-out Qvintip group, adjusted relative risks for the Qvintip and Evalyn Brush opt-in groups were 0.41 (95% confidence interval (CI) 0.37-0.45) and 0.44 (95% CI 0.40-0.49), respectively. Participation was associated with living place, citizenship, and education. Self-sampling was well accepted: 98% agreed that it was easy to use, 88% preferred it as a screening method in future. CONCLUSIONS: The results show the feasibility and good acceptance of HPV self-sampling among long-term screening non-attenders in Estonia.

Prevalence of macrolide and fluoroquinolone resistance-mediating mutations in Mycoplasma genitalium in five cities in Russia and Estonia.

BACKGROUND AND OBJECTIVE: Resistance in the sexually transmitted bacterium Mycoplasma genitalium to all recommended therapeutic antimicrobials have rapidly emerged. However, to date, internationally reported resistance surveillance data for M. genitalium strains circulating in Eastern Europe are entirely lacking. The aim of this study was to estimate the prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium in four cities in Russia and one in Estonia, 2013-2016. MATERIALS AND METHODS: Consecutive urogenital samples found positive for M. genitalium during diagnostic testing were retrospectively analyzed for resistance-associated mutations in the 23S rRNA and parC genes using pyrosequencing and conventional Sanger sequencing, respectively. RESULTS: In total, 867 M. genitalium positive samples from 2013-2016 were analyzed. Macrolide resistance-associated mutations were detected in 4.6% of the samples from Russia (0.7-6.8% in different cities) and in 10% of the samples from Estonia. The mutations A2059G and A2058G were highly predominating in both Russia and Estonia, accounting together for 90.9% of the cases positive for nucleotide substitutions in the 23S rRNA gene. The rates of possible fluoroquinolone resistance-associated mutations were 6.2% in Russia (2.5-7.6% in different cities) and 5% in Estonia. The mutations S83I and S83N were the most frequent ones in Russia (24.4% each), whereas D87N highly predominated in Estonia (83.3% of all fluoroquinolone resistance-associated mutations). Approximately 1% of the samples in both countries harbored both macrolide and possible fluoroquinolone resistance-associated mutations, with A2058G and S83I being the most frequent combination (37.5%). CONCLUSIONS: The prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium was 4.6% and 6.2%, respectively, in Russia, and 10% and 5%, respectively, in Estonia. Despite the relatively low rates of macrolide and fluoroquinolone resistance in these countries, antimicrobial resistance surveillance and testing for resistance-associated mutations in M. genitalium positive cases would be valuable.

Influence of sexual intercourse on genital tract microbiota in infertile couples.

Several studies have suggested the association of disturbed genital tract microbiota with infertility. Our aim was to clarify the influence of sexual intercourse on partner's genital tract microbiota in infertile couples. Seventeen couples were studied, and in 5 men inflammatory prostatitis (IP) was diagnosed. Semen samples were collected during menstruation of the female counterpart, two self-collected vaginal samples were taken 3-5 days later - before intercourse and 8-12 h after intercourse. Ureaplasma parvum was found in 59% of women, its prevalence was higher in women whose partner had IP, as well as in half of their male partners. Sexual intercourse caused significant shifts in vaginal microbiota - increase of Nugent score and shifts in cultured microbiota (emergence and disappearance of several species). These changes were less expressed in the presence of normal vaginal microbiota but more prominent in the partners of IP men. These changes may interfere with fertilization.

Automatic identification of species-specific repetitive DNA sequences and their utilization for detecting microbial organisms.

MOTIVATION: The concentration of pathogen DNA in biological samples is often very low. Therefore, the sensitivity of diagnostic tests is always a critical factor. RESULTS: We have developed a novel computational method that identifies species-specific repeats from microbial organisms and automatically designs species-specific PCR primers for these repeats. We tested the methodology on 30 randomly chosen microbial species and we demonstrate that species-specific repeats longer than 300 bp exist in all these genomes. We also used our methodology to design species-specific PCR primers for 86 repeats from five medically relevant microbial species. These PCR primers were tested experimentally. We demonstrate that using species-specific repeats as a PCR template region can increase the sensitivity of PCR in diagnostic tests. AVAILABILITY AND IMPLEMENTATION: A web version of the method called MultiMPrimer3 was implemented and is freely available at (http://bioinfo.ut.ee/multimprimer3/).

Coinfection of Chlamydia trachomatis, Ureaplasma urealyticum and human papillomavirus among patients attending STD clinics in Estonia.

Women visiting Estonian STD clinics were subjected to PCR assay for human papillomavirus (HPV), Chlamydia trachomatis and Ureaplasma urealyticum biovar 2. The overall prevalence of coinfection was 8%. The chlamydial infection was found to be associated with HPV, especially with high-risk HPV (OR=2.5, p<0.005) and most significantly in women over 41 y of age. C. trachomatis infection also occurred more frequently in U. urealyticum-infected than in U. urealyticum-free patients (OR=2.6, p=0.02). U. urealyticum infection did not associate with HPV status. The clinical significance of the association between C. trachomatis and U. urelyticum infection remains to be elucidated.