Ilkka Kalliala

• M.D., Ph.D.
• Consultant at Helsinki University Central Hospital

Epigenetic alterations are essential in the development of cancers, while epigenome‐wide exploration in cervical cancer has been limited. In this epigenome‐wide association study (EWAS) we explore differential DNA methylation signatures associated with CIN (cervical intraepithelial neoplasia) grade 3 and cervical cancer to better understand potenti...

Introduction To evaluate predicting clinical factors for regression and progression of cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) in young women during two years of active surveillance. Material and Methods This was a single‐center prospective observational cohort study. Women under 31 years of age giving written informed consent with...

Evidence on the diagnosis and management of women with primary lymphoma of the uterine cervix (PLUC) is limited. The present study performed a systematic review of the literature and provided an overview of the reported cases of PLUC. A total of 213 reports were included, which comprised 339 patients with PLUC. The mean age of the patients was 48.5...

Background Amplicon sequencing of kingdom-specific tags such as 16S rRNA gene for bacteria and internal transcribed spacer (ITS) region for fungi are widely used for investigating microbial communities. So far most human studies have focused on bacteria while studies on host-associated fungi in health and disease have only recently started to accum...

Background Peripartum asphyxia is one of the main causes of neonatal morbidity and mortality. In moderate and severe cases of asphyxia, a condition called hypoxic-ischemic encephalopathy (HIE) and associated permanent neurological morbidities may follow. Due to the multifactorial etiology of asphyxia, it may be difficult prevent, but in term neonat...

Objective To compare the cost‐effectiveness of different treatments for cervical intraepithelial neoplasia (CIN). Design A cost‐effectiveness analysis based on data available in the literature and expert opinion. Setting England. Population Women treated for CIN. Methods We developed a decision‐analytic model to simulate the clinical course of...

Introduction/Background Around one fifth of endometrial cancers (EC) are diagnosed in premenopausal women. The standard treatment for EC, its precursor: endometrial hyperplasia with atypia (EHA), and unresolved endometrial hyperplasia (EH) is a hysterectomy. Fertility-sparing treatment has more recently been recognised as a viable option for those...

We report the short- and long-term results of the SOLIDARITY Finland on mortality and other patient-important outcomes in patients hospitalised for COVID-19. Between 08/2021 and 03/2023, we randomised 156 patients in 15 hospitals. In the imatinib group, 7.2% of patients had died at 30 days and 13.3% at 1 year and in the standard of care group 4.1%...

OBJECTIVE To provide procedure-specific estimates of the risk of symptomatic venous thromboembolism (VTE) and major bleeding in gynecologic non-cancer surgeries. DATA SOURCES We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar. Furthermore, we performed separate searches for randomized trials addressing the ef...

Objective To assess whether electrical impedance spectroscopy (EIS) as an adjunctive technology enhances the performance of colposcopy. Design Prospective cohort study. Setting University Hospital colposcopy clinic. Participants Colposcopy with EIS for 647 women and conventional colposcopy for 962 women. Interventions Comparison of the performa...

Non- Lactobacillus -dominated vaginal microbiota has been associated with poor gynecologic health and complications during pregnancy. Lactobacilli and especially Lactobacillus crispatus associate with good reproductive health and dominate the microbiota during healthy pregnancy. We examined whether the composition of vaginal microbiota at the time...

Introduction/Background Epigenetic alterations are essential in the development of many cancers and can occur years in advance of histopathological change. Interest in methylation testing for enhanced cervical screening is increasing but epigenome-wide exploration has been limited and the best methylation markers are yet unknown. In this epigenome-...

Introduction/Background Cervical cancer is the fourth most common malignancy in women worldwide. Current cervical screening programmes use a primary screening test of high-risk HPV (hr-HPV) testing or cytology to identify at risk women. hrHPV testing has a high sensitivity but low specificity for high-grade CIN and Cancer. As a result, DNA methylat...

Introduction/Background The efficacy of HPV vaccination on the risk of recurrent cervical disease related to HPV infection in individuals undergoing local surgical treatment constitutes a matter of debate. Methodology In this study we screened data sources for studies reporting on the risk of recurrent disease related to HPV infection after local...

Background Persistent infection by oncogenic human papillomavirus (HPV) is necessary although not sufficient for development of cervical cancer. Behavioural, environmental, or comorbid exposures may promote or protect against malignant transformation. Randomised evidence is limited and the validity of observational studies describing these associat...

Background Amplicon sequencing of kingdom-specific tags such as 16S rRNA gene for bacteria and internal transcribed spacer (ITS) region for fungi are widely used for investigating microbial communities. So far most human studies have focused on bacteria while studies on host-associated fungi in health and disease have only recently started to accum...

Study question Does the composition of vaginal microbiota affect the success of IVF-ET? Does vaginal microbiota profile change intra-individually from IVF-ET to early pregnancy? Summary answer L. crispatus is associated with successful IVF outcome. The individual composition of vaginal microbiota tends to shift towards Lactobacillus-dominance betw...

Introduction Human papillomavirus (HPV) is necessary but not sufficient for cervical cancer development. During cervical carcinogenesis, methylation levels increase across host and HPV DNA. DNA methylation has been proposed as a test to diagnose cervical intraepithelial neoplasia (CIN); we present a protocol to evaluate the accuracy of methylation...

Background Peripartum asphyxia is one of the main causes of neonatal morbidity and mortality. In moderate and severe cases of asphyxia, a condition called hypoxic-ischemic encephalopathy (HIE) and associated permanent neurological morbidities may follow. Due to the multifactorial etiology of asphyxia, it may be difficult prevent, but in term neonat...

Objective To study the busy day effect on selected neonatal adverse outcomes in different sized delivery hospitals and in the entire nationwide obstetric ecosystem. Design A cross‐sectional register study. Setting The lowest and highest 10% of the daily delivery volume distribution were defined as quiet and busy days, respectively. The days betwe...

Background Diabetes has reached epidemic proportions in recent years with serious health ramifications. The aim of this study was to evaluate the strength and validity of associations between diabetes and anti-diabetic interventions and the risk of any type of gynaecological or obstetric conditions. Methods Design: Umbrella review of systematic re...

Background Coronavirus disease 2019 (COVID-19) patients frequently suffer from long-term sequelae, often called “long COVID” or “post COVID-19 condition”. Remdesivir, given in early disease, decreases the risk of hospitalization and potentially mortality. No randomized trials have thus far published long-term follow-up data on any COVID-19 drug tre...

Introduction/Background Pharmacological thromboprophylaxis involves balancing lower risk of venous thromboembolism (VTE) against higher risk of bleeding, a trade-off that critically depends on VTE and bleeding risks in the absence of prophylaxis (baseline risk). Baseline risks likely vary between procedures, but their magnitude remains uncertain. A...

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At o...

Objective The gold standard of cervical intraepithelial neoplasia (CIN) treatment is large loop excision of the transformation zone (LLETZ) after histopathological diagnosis from punch biopsies. In addition, treatment may be appropriate at initial colposcopy. Our objective was to study the applicability of immediate treatment strategy according to...

Abstract Objective To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment. Design Systematic review and meta-analysis Data sources PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov were...

Background Vaginal microbiome and the local innate immune defense, including the complement system, contribute to anti- and proinflammatory homeostasis during pregnancy and parturition. The relationship between commensal vaginal bacteria and complement activation during pregnancy and delivery is not known. Objective To study the association of the...

Background The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear. We aimed to determine the risks of treatment failure and preterm birth associated with various treatment techniques. Methods In this systematic review and network meta-an...

Study question Does endometrial or vaginal microbiota composition associate with recurrent pregnancy loss (RPL)? Summary answer Reduced relative abundance of Lactobacillus crispatus in endometrium and increased relative abundance of Gardnerella vaginalis in endometrium and vagina were associated with RPL. What is known already Dysbiotic vaginal m...

Background: Vaginal microbiota and its potential contribution to preterm birth is under intense research. However, only few studies have investigated the vaginal microbiota in later stages of pregnancy or at the onset of labour. Methods: We used 16S rRNA gene amplicon sequencing to analyse cross-sectional vaginal swab samples from 324 Finnish wo...

Research question: Is the composition of the endometrial or vaginal microbiota associated with recurrent pregnancy loss (RPL)? Design: Endometrial and vaginal samples were collected from 47 women with two or more consecutive pregnancy losses and 39 healthy control women without a history of pregnancy loss, between March 2018 and December 2020 at...

Background: Daily delivery volume might affect the quality of obstetric care. We explored the busy day effect on selected obstetrical interventions and epidural analgesia performed during labour in different sized delivery hospitals and on the Finnish obstetric ecosystem. Methods: We conducted a cross-sectional study on Finnish Medical Birth Reg...

Several non-genetic factors have been associated with ovarian cancer incidence or mortality. To evaluate the strength and validity of the evidence we conducted an umbrella review of the literature that included systematic reviews/meta-analyses that evaluated the link between non-genetic risk factors and ovarian cancer incidence and mortality. We se...

This authoritative textbook provides a much-needed guide for postgraduate trainees preparing for the European Board and College of Obstetrics and Gynaecology (EBCOG) Fellowship examination. Published in association with EBCOG, it fully addresses the competencies defined by the EBCOG curriculum and builds the clinical practice related to these compe...

Vaginal microbiota and its potential contribution to preterm birth has been under intense research in recent years. However, only few studies have studied vaginal microbiota in later stages of pregnancy or at the onset of labor. We analyzed vaginal swab samples collected between 37- and 42-weeks of gestation from 324 Finnish women before elective c...

Background Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on t...

Introduction/Background* Cervical cancer is one of the most prevalent and leading cause of cancer mortality for women worldwide. Persistent infection with HPV is associated with the development of cervical cancer. Although most infections are cleared by the immune response, the factors related to persistent infection and carcinogenesis are less wel...

While the contributing factors leading to endometriosis remain unclear, its clinical heterogeneity suggests a multifactorial causal background. Amongst others, caffeine has been studied extensively during the last decade as a putative contributing factor. In this systematic review and meta-analysis, we provide an overview/critical appraisal of stud...

Purpose The aim of this study is to present a single department’s experience on cervical cancer cases following previous excision of cervical intraepithelial neoplasia (CIN) and to discuss potential pathogenesis. Methods Nine cervical cancer cases meeting the inclusion criteria, with available pathological and follow-up data, were considered eligi...

Background: Genome-wide association studies (GWAS) have not identified replicable genetic risk loci for stress or urgency urinary incontinence. Methods: We carried out a discovery stage case control GWAS in three independent discovery cohorts of European women (n=8,979) for stress incontinence, urgency incontinence, and any incontinence phenotyp...

Risk factors for the different human papillomavirus (HPV) genotypes are not well understood, although the risk of cancer is known to vary among them. Our aim was to evaluate the association of diverse behavioral and reproductive factors with genotype-specific HPV prevalence among 879 unvaccinated women aged 18–75 years referred to the colposcopy cl...

Background Most uterine cervical high-risk human papillomavirus (HPV) infections are transient, with only a small fraction developing into cervical cancer. Family aggregation studies and heritability estimates suggest a significant inherited genetic component. Candidate gene studies and previous genome-wide association studies (GWASs) report associ...

Background: Amplicon sequencing of kingdom-specific tags such as 16S rRNA gene for bacteria and internal transcribed spacer (ITS) region for fungi are widely used for investigating microbial populations. So far most human studies have focused on bacteria while studies on host-associated fungi in health and disease have only recently started to accu...

A registry-based follow-up of pregnancy data until the end of 2014 was conducted based on a community-randomized trial to assess human papillomavirus (HPV) vaccination strategies and a reference cohort from the same community with no intervention. Our objective was to determine whether prophylactic HPV vaccination (three doses of Cervarix® (AS04-HP...

Background Human pregnancy alters profoundly the immune system. The local involvement and mechanisms of activation of the complement system in the cervicovaginal milieu during pregnancy and delivery remain unexplored. Objectives To determine whether normal pregnancy and delivery are associated with local activation of complement or changes in the...

High-quality colposcopy is essential in cervical cancer prevention. We performed a multicentre prospective interventional pilot-study, evaluating the effect of a six-hour case-based colposcopy course on short- and long-term learning of colposcopy-related knowledge, diagnostic accuracy levels and confidence. We recruited 213 colposcopists participat...

Colposcopy is often used in follow-up after treatment for cervical intraepithelial neoplasia (CIN) despite its marked inter-observer variability and low sensitivity. Our objective was to assess the role of colposcopy in post-treatment follow-up in comparison to hrHPV (high-risk human papillomavirus) testing, cytology, and cone margin status. Altoge...

Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissu...

Background: Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies af...

Compared to other human microbiota, vaginal microbiota is fairly simple with low bacterial diversity and high relative abundance of Lactobacillus species. Lactobacillus dominance is even more pronounced during pregnancy. Genetic factors, such as ethnicity, along with environmental, individual and lifestyle factors all have an impact on vaginal micr...

Introduction/Background Persistent infection with high-risk human papillomavirus (HPV) is causally associated with cervical cancer. However, only ∼1% of women with HPV infection progress to cervical neoplasia (CIN). It is estimated that heritability may explain 25–30% of total variation in liability for cervical cancer. Common genetic variants have...

Introduction/Background Methylation of viral DNA has been proposed as a novel biomarker for triage of HPV positive women at screening.This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine its diagnostic test accuracy in detecting high-grade cervical intra-epithelial neoplasia (C...

Background: Methylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus (HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detecting high-grade cervical intra-epitheli...

Introduction/Background Ovarian cancer is one the deadliest gynaecological malignancies and many risk factors for its occurrence have been described. Despite the wealth of data on the subject, the robustness of evidence available has not yet been extensively evaluated. This review aims to fill this gap and assess the strength and validity of eviden...

Introduction/Background Diabetes mellitus (DM) continues to affect a large proportion of the population and its incidence is on the rise. Many complications associated with it, such as gynaecological cancers, are becoming increasingly apparent. Due to conflicting evidence, it is unknown which outcomes diabetic women are most at risk of. Therefore,...

Introduction/Background Several approaches to fertility-sparing surgery in women with cervical cancer exist. Differences in radicality of parametrial excision are thought to exist according to surgical technique. Minimal access approaches may offer benefits in terms of enhanced patient recovery and nerve-sparing, however comparative oncological saf...

Introduction/Background Surgical management of presumed early stage cervical cancer presents challenges as clearance of surgical margins avoids adjuvant chemoradiotherapy that can substantially increase morbidity and may allow fertility preservation in young women. Improved intra-operative diagnostic tools have the potential to improve outcomes. In...

Introduction: There are several local treatment methods for cervical intraepithelial neoplasia that remove or ablate a cone-shaped part of the uterine cervix. There is evidence to suggest that these increase the risk of preterm birth (PTB) and that this is higher for techniques that remove larger parts of the cervix, although the data are conflict...

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in...

Introduction Local treatments for cervical intraepithelial neoplasia (CIN) and microinvasive disease remove or ablate a cone-shaped part of the uterine cervix containing the abnormal cells. A trend toward less radical techniques has raised concerns that this may adversely impact the rates of precancerous and cancerous recurrence. However, there has...

Background: There is no baseline prognostic test to ascertain whether cervical intraepithelial neoplasia (CIN) will regress or progress. The majority of CIN regress in young women and since local treatments are known to increase the risk of adverse pregnancy outcomes interventions need to be sparing. We investigated the ability of a DNA methylatio...

Background and aim: Age-specific type-distribution of high-risk human papillomavirus (hrHPV) in cervical precancerous lesions is subject to change in the HPV vaccination era. Knowing the pre-vaccination type-distribution helps to anticipate changes induced by mass vaccination and optimize screening. Methods: We recruited 1279 women referred to c...

Recent research on vaginal microbiota relies on high throughput sequencing while microscopic methods have a long history in clinical use. We investigated the correspondence between microscopic findings of Pap smears and the vaginal microbiota composition determined by next generation sequencing among 50 asymptomatic women. Both methods produced coh...

Although many risk factors could have causal association with endometrial cancer, they are also prone to residual confounding or other biases which could lead to over‐ or underestimation. This umbrella review evaluates the strength and validity of evidence pertaining risk factors for endometrial cancer. Systematic reviews or meta‐analyses of observ...

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. We conducted a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 was associated with gestational duration; the association was replicated in...

Persistent genital chlamydial infection may lead to tubal factor infertility (TFI). Chlamydia trachomatis TroA and HtrA are proteins expressed during persistent chlamydial infection in vitro. We studied serum IgG antibody response against these proteins by EIA in women with TFI and in subfertile women without tubal pathology. Altogether, 22 of 258...

Aim: To explore current practice in fertility-sparing surgery for cervical cancer in the UK. Materials and methods: A web-based structured questionnaire was designed and circulated to all members of the British Gynaecological Cancer Society. Results: From 111 recipients, a total of 49 responses were collected. The majority of centres treated b...

Problem What is the role of past Chlamydia trachomatis infection in unexplained infertility? Method of study This is a prospective study of the impact of past C. trachomatis infection on pregnancy rates in 96 women with unexplained infertility. Both humoral and cell‐mediated immune responses (CMI) against C. trachomatis were studied. Serum C. trac...

Background/Objectives: Cervical cancer and its precancerous form cervical intraepithelial neoplasia (CIN) commonly affect women of reproductive age. Fertility-preserving trachelectomy procedures are available, but if the excisional margins are not cancer-free, as is the case in up to 33% of procedures, these women must undergo a hysterectomy, there...

Objective To estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as compliance with follow-up protocols. Design Systematic review and meta-analysis. Data sources Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature...

Supplementary information: additional information supplied by authors

Background: The mean age of women undergoing local treatment for pre-invasive cervical disease (cervical intra-epithelial neoplasia; CIN) or early cervical cancer (stage IA1) is around their 30s and similar to the age of women having their first child. Local cervical treatment has been correlated to adverse reproductive morbidity in a subsequent p...

Objective To study the strength and validity of associations between adiposity and risk of any type of obstetric or gynaecological conditions. Design An umbrella review of meta-analyses. Data sources PubMed, Cochrane database of systematic reviews, manual screening of references for systematic reviews or meta-analyses of observational and interve...

Appendix 1: Supplementary methods

Appendix 2: Supplementary tables A-I and figure

Background Molecular methods such as next-generation sequencing are actively being employed to characterize the vaginal microbiota in health and disease. Previous studies have focused on characterizing the biological variation in the microbiota, and less is known about how factors related to sampling contribute to the results. Our aim was to invest...

Additional tables and figures. (PDF)