Grzegorz Szewczyk

Background/Objectives: Persistent infection with high-risk HPV genotypes accounts for the development of a substantial portion of anogenital and oropharyngeal malignancies. Patients with primary and secondary immunodeficiency or those receiving immunosuppressive therapy, including transplant recipients and patients affected by rare diseases, are vulnerable to particularly severe clinical manifestations of infection. While HPV vaccination constitutes primary prevention, patients with HPV-associated disease remain at risk of reinfection or subsequent infection with alternative genotypes following surgical treatment and may benefit from peri-operative vaccination regimens. This study aimed to evaluate long-term outcomes of HPV vaccination following surgical management of condyloma acuminata in patients with concurrent high-risk genotype infection. Methods: 350 patients with condyloma acuminata and HPV-16 or -18 co-infection confirmed by histopathological examination and PCR genotyping (oral cavity, vulva, vagina, penis, anoderma), including a subgroup with primary or acquired immunodeficiency or chronic immunosuppressive regimens, underwent surgical treatment, receiving simultaneous immunization with the first dose (subsequent completion of full regimen over 12 months) of the bivalent Cervarix vaccine (170 patients) or the quadrivalent Gardasil vaccine (180 patients). A follow-up examination, including HPV genotyping (16/18/31/35), was performed after 6 and 12 months following regimen completion. After 36 months, a standard clinical examination was performed, and in doubtful cases, supplemented with genotyping and biopsy/cytology. Observation was continued in subsequent years (5, 10, and >15 years). Results: Condyloma acuminata requiring removal were observed in 5% of the patients in follow-up at 36 months, with no significant statistical difference between vaccine groups. No cellular atypia or malignant transformation in the form of squamous cell carcinoma was observed. Genotyping did not detect HPV-16/18/31/35 infection in the follow-up examinations. Conclusions: In this uncontrolled, single-arm cohort, peri-operative initiation of either the bivalent or quadrivalent HPV vaccine was associated with a low rate of clinically apparent condyloma acuminata recurrence and no detectable HPV-16/18/31/35 infection during follow-up.

Background: The first-trimester ultrasound (11 + 0 to 13 + 6 weeks) is primarily used for aneuploidy screening, yet its potential for early identification of major fetal structural anomalies in an unselected population continues to be explored. This study evaluated the clinical yield and feasibility of a systematic first-trimester fetal anatomy assessment in a regional setting. Methods: This retrospective single-center study included 500 consecutive singleton pregnancies undergoing routine first-trimester ultrasound between 11 + 0 and 13 + 6 weeks of gestation. All examinations were performed by a single certified sonographer using an extended anatomical protocol according to ISUOG and FMF guidelines. The study center serves a regional population of approximately 400,000 inhabitants in eastern Mazovia, Poland. Cases with suspected anomalies underwent a detailed diagnostic work-up, including a targeted anomaly scan, early fetal echocardiography, and invasive genetic testing when clinically indicated. Results: Major fetal structural anomalies were suspected in 17 out of 500 fetuses (3.4%) during the first-trimester scan. Of the 17 suspected cases, 14 were confirmed on subsequent evaluation (14/17, 82.4%; 95% CI 56.6–96.2%), two were false-positives (11.8%), and one patient was lost to follow-up. Four fetuses (23.5%) presented with multiple anomalies involving different organ systems, with congenital heart defects being the most prevalent. A notable observational cluster of three cases of acrania/exencephaly was identified. Remarkably, only three of the confirmed affected cases (21.4%) presented with a nuchal translucency measurement above the 95th percentile. Conclusions: Integration of a systematic first-trimester fetal anatomy assessment allowed the identification of suspected major structural anomalies in 3.4% of fetuses in an unselected regional population. With a confirmation rate of 82.4% among screen-positive cases, these findings demonstrate the clinical feasibility of detailed first-trimester anatomical assessment in a regional setting.

Background/Objectives: Persistent infection with high-risk HPV genotypes accounts for the development of a substantial portion of anogenital and oropharyngeal malignancies. Patients with primary and secondary immunodeficiency or those receiving immunosuppressive therapy, including transplant recipients and patients affected by rare diseases, are vulnerable to particularly severe clinical manifestations of infection. While HPV vaccination constitutes primary prevention, patients with HPV-associated disease remain at risk of reinfection or subsequent infection with alternative genotypes following surgical treatment and may benefit from peri-operative vaccination regimens. This study aimed to evaluate long-term outcomes of HPV vaccination following surgical management of condyloma acuminata in patients with concurrent high-risk genotype infection. Methods: 350 patients with condyloma acuminata and HPV-16 or -18 co-infection confirmed by histopathological examination and PCR genotyping (oral cavity, vulva, vagina, penis, anoderma), including a subgroup with primary or acquired immunodeficiency or chronic immunosuppressive regimens, underwent surgical treatment, receiving simultaneous immunization with the first dose (subsequent completion of full regimen over 12 months) of the bivalent Cervarix vaccine (170 patients) or the quadrivalent Gardasil vaccine (180 patients). A follow-up examination including HPV genotyping (16/18/31/35) was performed after 6 and 12 months following regimen completion. After 36 months a standard clinical examination was performed, and in doubtful cases, supplemented with genotyping with biopsy/cytology. Observation was continued in subsequent years (5, 10, and >15 years). Results: Condyloma acuminata requiring removal were observed in 5% of the patients in follow-up at 36 months, with no significant statistical difference between vaccine groups. No cellular atypia or malignant transformation in the form of squamous cell carcinoma was observed. Genotyping did not detect HPV-16/18/31/35 infection in the follow-up examinations. Conclusions: In this uncontrolled, single-arm cohort, peri-operative initiation of either the bivalent or quadrivalent HPV vaccine was associated with a low rate of clinically apparent condyloma acuminata recurrence and no detectable HPV-16/18/31/35 infection during follow-up.

From an immunological perspective, infertility mechanisms encompass not only fertilization but also implantation, as well as both early and late pregnancy loss. Growing attention is being directed towards the influence of systemic disorders on reproductive outcomes. The immune system plays a fundamental and regulatory role in human reproduction. Immunological factors may affect multiple stages of this process, potentially justifying their inclusion in extended diagnostic pathways. The impact of autoimmunity and the presence of various antibodies on reproductive functions is discussed. Special attention is given to the immunomodulatory role of progesterone in reproduction and a state of impaired progesterone action—luteal deficiency. Endometriosis is also highlighted as a disorder both associated with infertility and underpinned by a strong immunological basis. The usefulness of assessing lymphocyte subpopulation balance, cytokine profiles, and Th1/Th2 immune response in the diagnostic work-up of infertility is addressed. Furthermore, the prospect for a role of local and systemic infections, subclinical inflammation and microbial colonization is shown. Tests applied in the evaluation of implantation and placental development disorders are discussed. Adequate immunological diagnostics and accurate identification of the underlying causes of infertility facilitate effective therapeutic strategies and can substantially increase the likelihood of achieving a successful pregnancy.

The development of low-resistance blood flow within the developing placenta in the early weeks of pregnancy requires trophoblast invasion of the uterine spiral arteries. Therefore, understanding the migration and differentiation of trophoblasts is necessary. Recently, researchers have focused increasingly on the regulation of the response of endovascular extravillous trophoblasts (enEVTs) to mechanical stimuli associated with shear stress. The starting point for these studies is that enEVTs, which adopt a pseudoendothelial phenotype, functionally resemble endothelial cells in terms of ability to promote angiogenesis, vascular remodeling and cell–cell communication. The complex process of mechanotransduction requires the coordinated participation of many types of mechanoreceptors, whose activated signaling pathways are translated into whole-cell mechanosensing involving components of the cytoskeleton and extracellular matrix. The aim of this review is to comprehensively present the current knowledge on the importance of mechanical stimuli associated with shear stress in the development of local changes in the vascular system at the site of blastocyst implantation. The characteristics of individual mechanoreceptors are determined, and the most important factors influencing mechanotransduction are discussed. Understanding the importance of mechanosensing disorders in trophoblasts in the pathogenesis of unexplained recurrent abortions or preeclampsia may be helpful in the development of new therapeutic strategies based on the regulation of mechanotransduction in response to shear stress.

Background: We assessed the relationship between uterine artery (UtA) indices and the occurrence of obstetrical complications in twin pregnancies. Methods: It was a longitudinal, prospective observation of the UtA indices and obstetric outcomes in twin pregnancies between 11 weeks of gestation and delivery. We used a logistic regression model with reliable estimators of standard errors considering the longitudinal structure. In 150 patients with twin pregnancies, 1086 ultrasound examinations were performed. The analysis incorporated nomograms for singletons and dichorionic (DC) twins. Results: In twin pregnancies, we observed a positive relationship between UtA indices and obstetrical complications (OR = 1.32, p = 0.043 for standardized PI and OR = 1.38, p = 0.018 for standardized RI). The risk increased with increasing UtA indices. There was a significant positive relationship between the UtA indices and analyzed pathologies in DC twins. We observed that both DC twins’ UtA indices below the 5th percentile were associated with favorable outcomes, while those above the 95th percentile were associated with adverse outcomes. According to the singleton nomograms, only the UtA PI above the 95th percentile showed significance. In MC twins, only significantly elevated UtA indices above the upper limit of nomogram were associated with adverse outcomes. Conclusions: The UtA nomogram for singleton and DC twins may be used in the prediction of twin pregnancy outcome, but DC nomograms are more accurate. The mechanism of obstetric complications in MC twins differs, and it requires further research. However, it seems that DC twin nomograms can be used in MC twins, but they will be less effective.

Background: Primary vaginal cancer is a rare gynecological condition. We present a case of complete utero-vaginal prolapse complicated by primary invasive vaginal carcinoma. To our knowledge, only a few similar cases have been reported in our region. Case Report: A 77-year-old woman, gravida two and para two, was admitted for treatment of pelvic organ prolapse. The patient reported an eight-year history of uterine bulging but had not used a pessary. The gynecological examination revealed a complete manually irreducible utero-vaginal prolapse with an ulcerative lesion on the right posterolateral vaginal wall. The histological examination diagnosed an HPV-independent keratinizing squamous cell carcinoma, grade I. Comprehensive imaging showed no evidence of metastasis. The patient underwent radical hysterectomy, bilateral adnexectomy, complete resection of the vaginal mass, and pelvic lymphadenectomy. The histopathological examination confirmed clear surgical margins. According to the International Federation of Gynecology and Obstetrics (FIGO) staging system, the disease was classified as stage I vaginal cancer. Postoperatively, the patient received radiotherapy (45 Gy) and high-dose-rate brachytherapy (14 Gy). Conclusions: The co-occurrence of vaginal cancer and utero-vaginal prolapse is exceedingly rare. Surgical intervention followed by radiotherapy is the most common treatment approach. Given the aggressive nature of the disease, comprehensive follow-up is essential. Further research is needed to determine whether long-term genital prolapse increases the risk of vaginal carcinoma.

Background/Objectives: Hypertensive disorders of pregnancy constitute one of the principal reasons for maternal and perinatal morbidity and mortality worldwide. Identification of molecular mechanisms causing placental dysfunction resulting in gestational hypertension is crucial in the development of new methods of prevention and treatment. The aim of this case-control study was to assess changes in miRNA expression, and biomarkers such as NT-proBNP and galectin-3, in women with uncomplicated pregnancies and hypertensive disorders of pregnancy. Methods: This was a case-control study. We included 61 women with uncomplicated pregnancies and 31 women with hypertensive disorders of pregnancy (21 women with gestational hypertension and 10 women with chronic hypertension). Blood sample collection was performed at 33 weeks of gestation. Expression and expression levels of 26 microRNAs, NTproBNP, and galectin-3 were measured. Results: Lower expression of microRNA 101a was observed in patients with hypertensive disorders of pregnancy. The expression of microRNA 101a was significantly lower in the group of patients with gestational hypertension, but not with chronic hypertension. Not only was the expression of microRNA 101a lower in all women with gestational hypertension but also in XYZ% it reached undetectable levels. Other studied microRNAs were similar in expression and concentration levels among both groups. In all women with hypertensive disorders of pregnancy, statistically significant correlations were detected between NT-proBNP concentrations and microRNA 133a (r = −0.68; p = 0.030) and microRNA 195 (r = 0.67; p = 0.030), and between galectin-3 and microRNA 195 (r = 0.46; p = 0.010), microRNA 133a (r = 0.44; p = 0.020), microRNA 222-2276 (r = 0.39; p = 0.050). Conclusions: microRNA 101a, a molecule associated with placental dysfunction in preeclampsia and with inhibition of cardiac fibrosis, has lower expression and concentration levels in gestational hypertension but not in chronic hypertension.

Background: Epithelioid Trophoblastic Tumor (ETT) and Placental Site Trophoblastic Tumor (PSTT) are two of the rarest GTNs that share certain features at diagnosis and management. Atypical Placental Site Nodule (APSN) is a relatively new entity considered as a premalignant lesion. Objectives and Methods: The aim of this review was to summarize the main characteristics of each of these entities, their diagnostic features, and their treatment’s standard of care including fertility-sparing treatments. Outcome: This study provides a thorough review of ETT, PSTT, and APSN. Conclusions: The reader will gain an insight view of these rare tumors arising from the intermediate trophoblast.

Sirtuins, especially SIRT1, play a significant role in regulating inflammatory response, autophagy, and cell response to oxidative stress. Since their discovery, sirtuins have been regarded as anti-ageing and longevity-promoting enzymes. Sirtuin-regulated processes seem to participate in the most prevalent placental pathologies, such as pre-eclampsia. Furthermore, more and more research studies indicate that SIRT1 may prevent pre-eclampsia development or at least alleviate its manifestations. Having considered this, we reviewed recent studies on the role of sirtuins, especially SIRT1, in processes determining normal or abnormal development and functioning of the placenta.