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Aim: The compliance of cytology and cytology combined with HPV HR test with cervical biopsy result, indicating the presence of cervical pathology was studied. Materials and Methods: The study enrolled 1,300 patients of Laboratory of Cervical Pathophysiology of University of Medical Sciences, who have had an abnormal Pap test and / or suspected cervical pathology following the clinical picture. The largest group consisted of 496 patients with cytological diagnosis of low-grade intraepithelial lesions (LSIL) and 388 patients diagnosed with atypical squamous cells of undetermined significance (ASC-US). Women age ranged from 16 to 79. In each of the women, cytological smear was performed, together with the DNA HPV HR (high-risk oncogenic) test and colposcopy with biopsy of suspected cervical changes. Results: After histopathological verification, 461 (35.4%) of abnormal results were obtained. Compliance of cytological diagnosis of ASC-US with abnormal cervical biopsy reached 15.2%, for atypical squamous cells - cannot exclude HSIL (ASC-H) - 40.4%, for LSIL - 42.1%, for high grade intraepithelial lesions (HSIL) - 63.8%, for atypical glandular cells (AGC) - 25.0%, and for suspected cancer - 77.8%, respectively. Considering HPV test result, the results of cytology with abnormal histopathology was by 5.8-25% higher, depending on the diagnosis, then the compliance of the single Pap smear. Conclusions: Cytology combined with molecular test, results in a significant increase in compliance of the cytological diagnosis with histopathological result. This compliance is the lowest for the cytological diagnosis of ASC-US and gradually increases with advancing cytological diagnosis, reaching the highest values when the cancer is suspected. Both cytological smear and HPV DNA HR test, applied separately, have false negative rates. [ABSTRACT FROM AUTHOR]

Background : High-grade advanced ovarian, fallopian tube, and primary peritoneal (HGAOC) cancers require both surgical and systemic treatment. The introduction of polyADP-ribose polymerase inhibitors (PARPis) has significantly improved outcomes. This study presents an analysis of HGAOC patients treated at a single center, following updated guidelines. Methods : We observed 437 women newly diagnosed with HGAOC at the Department of Gynecological Oncology between January 2018 and December 2023. Results : Since November 2022, first-line treatment has included bevacizumab and PARPi, regardless of residual disease post-cytoreductive surgery. In both BRCA1/2 -mutated and non-mutated groups, PARPi-based regimens increased significantly after May 2021 ( p < 0.01). Recurrence number emerged as a strong prognostic factor for survival ( p < 0.001), with each recurrence raising mortality risk by 80%. Median survival was 21 months for paclitaxel + platinum derivatives (PC), 27 months for PC + bevacizumab (BEV), and 30 months for PC + BEV + PARPi. Conclusions : The rapid adoption of modern therapies at our center has aligned treatment strategies with HRD status and global standards. However, variations in financial regulations and drug accessibility persist across countries. Despite these challenges, physicians should prioritize the most effective therapies available.

Introduction: Granulosa cell tumor (GCT) accounts for 3-5 % of all ovarian malignancies, being the most common among those originating from the sex cords and ovarian stroma. GCTs can be divided into juvenile and adult types, with the latter occurring mostly in perimenopausal women. These hormonally active tumors present diverse clinical manifestations, primarily related to elevated estrogen levels. The treatment is primarily surgical; other methods, mainly chemotherapy, are also used., Presentation of Cases: Three cases highlight the heterogeneity of GCTs. Case 1 involved a 34-year-old woman diagnosed with ovarian tumor during routine gynecological follow-up. Stage IA GCT was diagnosed. Fertility-sparing surgery followed by chemotherapy led to a favorable outcome, including two pregnancies. Case 2 involved a postmenopausal woman with a large pelvic mass. Surgery revealed a Stage IA GCT. Chemotherapy was stopped early due to complications. Case 3 featured a 47-year-old with acute abdominal symptoms caused by a ruptured GCT, leading to emergency surgery and subsequent radical treatment., Discussion: GCTs are hormonally active, causing symptoms such as abnormal bleeding or abdominal discomfort. Prognosis is generally favorable, especially in early-stage cases. Long-term surveillance is essential due to the potential for late recurrences. Fertility-sparing surgery is feasible in young patients, while chemotherapy is mainly used for advanced disease or recurrence., Conclusion: GCTs, in addition to being rare, present with a wide range of clinical manifestations. Individualized treatment based on patient age, tumor stage, and fertility plans is crucial for favorable outcomes. Long-term monitoring is recommended due to the risk of late recurrence., Competing Interests: Conflict of interest statement None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Vaccination against human papillomavirus (HPV) significantly reduces the incidence of HPV-related lesions worldwide. Considering the increasingly young age of patients in gynecological offices and earlier sexual initiation and potential contact with the HPV virus, doctors need the tools to verify diagnoses. Currently, women plan to pursue motherhood later, so it is necessary to consider whether sexual treatment in the form of, among others, loop electrosurgical excision procedures (LEEPs) may increase the risk of premature birth or difficulty dilating the cervix during labour. For this reason, to avoid the overtreatment of low-grade squamous intraepithelial lesions (LSILs), methylation testing may be considered. In patients with histopathologically confirmed high-grade squamous intraepithelial lesions (HSILs) during biopsy and, ultimately, a lower diagnosis, i.e., LSIL or no signs of atypia, methylation was found to be a useful tool. We performed a Pap smear, HPV genotyping, a punch biopsy, LEEP-conization (if needed), and methylation tests on 108 women admitted to the District Public Hospital in Poland. Women with a negative methylation test result were significantly more likely to be ultimately diagnosed with LSIL ( p = 0.013). This means that in 85.7% of the patients with HSIL, major cervical surgery could be avoided if the methylation test was negative. Methylation testing, as well as dual-staining and diagnostics detecting the mRNA transcripts of highly oncogenic types of HPV, might be used in the future in the diagnosis of pre-cancerous conditions, mainly of the cervix, and in HPV-dependent cervical cancer screening. The methylation test may also be used in the diagnosis and identification of lesions within the cervical canal, including those located deep within the frontal crypts, not visible even during a professional colposcopic evaluation of the cervix.

Objectives: to explore the opinions of pregnant and postpartum women on the services provided via remotely conducted consultation and to assess the sense of security of patients under the care conducted remotely my midwives and gynecologists., Material and Methods: An anonymous, self-administered survey questionnaire was completed by 86 women who had at least one telephone consultation with a gynecologist or midwife during pregnancy or after birth. The questionnaire was spread via social media between February 1 and August 1, 2022., Results: More than half of the surveyed group (51.2%) had 1-3 consultations performed remotely during pregnancy and 53.5% after birth. Phone call only was the most popular form of remote consultations performed during pregnancy (69.8%) and after birth (43.0%). Simple app was used in 10.5% consultations during pregnancy and 4.7% after birth. The predominant reason of the remotely conducted consultation during pregnancy and after birth was the need of getting the prescription or consultation of blood/urine test results (61.6%). Although phone-made medical consultations were a convenience and time-saver for most women, the preferred form of visit is to meet the caregiver in person., Conclusions: Special times, such pandemic was, requires a different, individual approach, and perhaps thanks to these experiences we will be able to behave wiser in future states of public health emergency. Teleconsultations were an acceptable form of medical consultation to discuss the results, effects of treatment or to write a referral or prescription.

Background: Cervical cancer is fourth the most common cancer in women worldwide. Due to the prevalence of human papillomavirus (HPV) in the population (80-90%), scientists are likely to discover even more associations of this pathogen with other diseases in the future. In recent years, In Situ Hybridization (ISH) assays that use automated signal-detecting methods in formalin-fixed, paraffin-embedded (FFPE) cervical tissue, such as the enzyme-categorized signal-detecting system, have shown a higher sensitivity. Objectives and Methods: To evaluate automatic signal detection of ISH assay for detecting HPV DNA, we compared the ability of an ISH probe, Inform HPV II and III (Ventana Medical Systems, Tucson, AZ), to that of PCR assays to detect HPV DNA in cervical tissue specimens with cervical intraepithelial neoplasia (CIN; CIN 1, 28 cases; CIN 2, 22 cases; and CIN 3, 20 cases) and normal cervix (2 cases). Results: Our findings showed a significant relation was confirmed between ISH III level and HPV outcome (positive/negative). Patients with positive HPV outcomes had significantly lower ISH III levels, MD = -7961.82 CI 95 [-17,230.00; -199.21], p = 0.005. Conclusions: Automatic signal detection of ISH assay is not particularly applicable to cervical tissue material. A more useful method of confirming the presence of HPV in the cervix is the HPV test with genotyping, as it allows for collecting a larger amount of material from the cervical disc and canal. The interpretation of a positive or negative ISH test must be guided in the context of clinical history and morphology.

Objectives: Genitourinary tract infections in pregnant women are one of the causes of abnormal pregnancy development including miscarriages, premature labor or premature rupture of membranes (PPROM). Atypical bacteria responsible for reproductive tract infections include Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum. Identification of pathogens and appropriately selected therapy can improve obstetric outcomes in patients with symptoms of threatened miscarriage or threatened preterm labor. The purpose of our study is to analyze the impact of reproductive tract infections with ureaplasma and mycoplasma bacteria during pregnancy., Material and Methods: In the presented study, we retrospectively analyzed the cases of 201 pregnant patients hospitalized in the Obstetrics and Gynecology Department of Poznan Regional Hospital in 2019-2022, who had a swab taken from external os area of the cervix for atypical bacteria - Ureaplasma and Mycoplasma. Only patients with symptoms of threatened miscarriage or threatened preterm labor were included in the study group. Microbiological tests were performed in the hospital laboratory with the Mycoplasma IST 3 test from Biomerieux., Results: We found a higher incidence of preterm labor in patients with symptoms of threatened preterm labor and a genital tract infection with Ureaplasma/Mycoplasma bacteria, compared to patients not infected with Mycoplasma/Ureaplasma - 31.1% vs 20% (p = 0.098). This observation in the case of Ureaplasma/Mycoplasma monoinfection group applied to 6 patients. - 75% of the group. Pregnant patients who had co-infection with other types of bacteria (48 patients in total) gave birth before 37 weeks of pregnancy in 27.1% of cases. We obtained a significant difference (p = 0.007) when comparing groups with positive and negative cultures for Ureaplasma/Mycoplasma by the presence of monoinfection/coinfection and the week of pregnancy in which delivery occurred. We also noted the effect of atypical bacterial infection for PPROM - this complication preceded preterm delivery in 40% of ureaplasma-positive patients, compared to 20% of PPROM without infection. We found a similar rate of preterm labor and pregnancy loss in Ureaplasma/Mycoplasma-positive patients who received antibiotic therapy (35.7%) compared to a group of pregnant women who did not receive treatment (31.6%)., Conclusions: Infection of the genital tract with atypical bacteria Ureaplasma and Mycoplasma has a negative impact on the course of pregnancy. Identification of the type of microorganisms in cervical canal secretions of pregnant patients with symptoms of threatened miscarriage or preterm labor seems crucial. The impact of antibiotic therapy though, requires further analysis.

Objectives: Free-of-charge vaccination against human papillomavirus (HPV) of 12-13-year-old teenagers was introduced on the 1st of June 2023 in Poland. Data on baseline HPV genotype cervical distribution are crucial to evaluate potential changes after full implementation of the vaccination program. We aimed at evaluating the status of HPV infection and distribution of HPV genotypes in cervical cytology of gynecological patients tested in one of the largest HPV laboratories in Poland., Material and Methods: Data on all HPV tests performed in ALAB Laboratoria Sp. z o. o. in Poland in 2018-2021 were analyzed, focusing on tests that identified genotypes: 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 44, 45, 51, 52, 53, 54, 56, 58, 59, 61, 62, 66, 67, 68, 70, 73, 81, 82, 83, 89. Distribution of HPV genotypes was assessed among HPV-positive women., Results: Among 11.151 medical records retrieved in women with valid HPV test results, 5.681 were positive (50.9%), of whom 2.929 were infected with a single genotype (51.6%). At least one high-risk (HR) genotype was detected in 4.351 women (76.6%). Among all HPV-positive women, the most common HR genotypes were HPV-16, HPV-31 and HPV-66 (24.0%, 11.3%, 11.3%, respectively). HPV-53 was the most prevalent among non-HR types (10.5%)., Conclusions: HPV-16 followed by HPV-31 and HPV-66 were the most frequent genotypes in the studied cohort. These results may be compared with the same methodology after full roll-out of HPV vaccination program in the future to track potential changes in HPV genotype distribution.

Objectives: Human papillomavirus (HPV) is the most widespread virus with oncogenic potential that infects humans and there is a need to look for the most effective screening method among the population. Understanding the role of HPV in cervical dysplasia and viruses typing increased the usage of HPV-based cervical cancer screening tests using genotyping., Material and Methods: We aim to assess the usefulness the Onclarity Test with extended genotyping and phenotyping of HPV in detecting cervical squamous intraepithelial lesions in 695 subjects who registered for regular cervical screening or due to abnormal LBC result or positive HPV results., Results: Incidence of positive HPV depended significantly on biopsy outcome (p < 0.001). It was the highest for patients with HSIL (92.5%), lower for patients with LSIL (57.9%) and with HPV outcome of biopsy (50.0%). The sensitivity of positive HPV for detecting HSIL was equal to 92.50% (95% CI: 79.61%-98.43%), and specificity equalled 55.26% (95% CI: 43.41-66.69%). Sensitivity of HPV positive for any of 16, 18, 31, 45, 51 or 52 genotypes but not belonging to the P1, P2 or P3 group for detecting HSIL equalled 62.50% (95% CI: 45.80-77.27%), specificity equalled 72.37% (95% CI: 60.91-82.01%)., Conclusions: The Onclarity test is characterised by high sensitivity and specificity in detecting CIN2+ lesions. Extended genotyping enables the identification of the most common oncogenic HPV types in the population. It can be used as a basic tool for secondary prevention or together with LBC.

Human papillomavirus (HPV) is a common sexually transmitted infection that can cause both benign and malignant lesions. HPV vaccines, preferably administered before the onset of sexual activity, have demonstrated remarkable efficacy in preventing HPV-related cancers. The impact of a healthcare provider's recommendation on HPV vaccine acceptance is substantial. Therefore, medical students must undergo thorough training in this domain. This study compares fundamental understanding and viewpoints regarding HPV and anti-HPV vaccines among Polish students pursuing medical and non-medical sciences. This study was based on the authors' questionnaire, and the results were statistically analyzed. The participants in this study were 1025 students (medical sciences students-520 respondents in total; and non-medical sciences students-505 respondents in total). According to the results, medical students' knowledge about the consequences of HPV infection and vaccination against HPV was significantly greater. To date, numerous publications have investigated the understanding of particular social, gender, parental, etc., groups about vaccination, but the knowledge of students at different universities-medical and other-has not been compared. Social awareness is still insufficient, even in groups of medical students. There is much to be done to educate and encourage preventive behavior in those not receiving primary prevention in early childhood.

The introduction of human papillomavirus vaccines revolutionized cervical cancer prevention. Our research hypothesis is that HPV vaccination affects the remission of HPV in cervical swabs. We provide a prospective, ongoing, 24-month, non-randomized study in HPV-positive women. We enrolled 60 patients with positive HPV swabs from the cervix (fifty-one vaccinated with the nine-valent vaccine against HPV and nine unvaccinated). Using an enzyme-linked immunosorbent assay, we determined IgG class antibodies of HPV in the patients' serums. Persistent HPV infection after vaccination was significantly less frequent in the nine-valent vaccinated group (23.5%) compared to the control group (88.9%; p < 0.001). Antibody level after vaccination was significantly higher in the vaccinated patients compared to the control group. The reactive antibody level was seen in the case of all patients in the vaccinated group and one-third of the unvaccinated group (33.3%, n = 3). The vaccination of HPV-positive patients may increase the chance of HPV remission in cervical swabs and may be a worthwhile element of secondary prevention in HPV-positive patients.

Ovarian cancer (OC) is the eighth most common cancer worldwide and is usually diagnosed in advanced stages. Despite many available data, no treatment results have been reviewed in Poland. This study enrolled 289 first-time patients treated between 2018 and 2021 by the Department of Oncology of the Poznań University of Medical Sciences (SKPP). The relationships among starting treatment in our centre, the type of first intervention, and the final decision were significant ( p < 0.001). Patients in the SKPP group were more likely to primarily have a laparoscopy and less likely to have an exploratory laparotomy. Neoadjuvant chemotherapy (NACT) after a laparotomy was less often a final decision among SKPP patients (9% vs. 22%), in contrary to NACT after a laparoscopy (23% vs. 4%). Factors affecting the shortening of progression-free survival (PFS) were an advanced stage of the disease, a histopathological diagnosis, the type of cytoreduction, and the final decision. Significance according to the final decision was revealed for PDS vs. NACT after a laparotomy ( p < 0.001) and for PDS vs. NACT after a laparoscopy ( p = 0.011). Our study supports the benefits of treating ovarian cancer in an oncology centre with a high patient throughput. Further observations might also answer the question about overall survival (OS).

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways., (© 2023. The Author(s).)

The prevalence and distribution of oncogenic human papillomavirus (HPV) genotypes in women who underwent screening for cervical cancer in the Wielkopolska region, Poland, were assessed, and the correlation of genotypes with the histological results was evaluated. Cervical samples were collected from 2969 women for cervical cancer screening. Participants were screened by liquid-based cytology and HPV genotyping ( n = 1654) and referred to colposcopy and punch biopsy ( n = 616) if recommended. HPV genotypes 16, 31, 52, 66, 53, and 51 are the most frequent types in the studied population. Genotypes 16 and 31 account for nearly one-fifth of the infections of diagnosed HPV infections. HPV 16, 31, and 52 are found in nearly 80% of premalignant HSIL lesions (CIN 2 and CIN 3). That leads to the conclusion that vaccination programs should cover as many types of HPV as possible and shows the urgent need to vaccinate the Polish population with a 9-valent vaccine.

We aim to describe the relationship between the immunohistochemical expression patterns of HPV E4 markers and the presence of HPV major capsid protein (L1) in cervical tissues obtained by biopsy of patients with abnormal liquid-based cytology (LBC) results, HR HPV infections, or clinically suspicious cervix. A novel HPV-encoded marker, SILgrade-E4 (XR-E4-1), and an HPV (clone K1H8) antibody were used to demonstrate the expression in terminally differentiated epithelial cells with a productive HPV infection in the material. A semiquantitative analysis was performed based on light microscope images. The level of E4 protein decreased with the disease severity. Patients with LSIL-CIN 1 and HSIL-CIN 2 diagnoses had significantly lower levels of HPV major capsid protein (L1) than those without confirmed cervical lesions. Our analysis confirms a higher incidence of L1 in patients with molecularly diagnosed HPV infections and excluded lesions of LSIL-CIN 1 and HSIL-CIN 2. Further studies on the novel biomarkers might help assess the chances of the remission of lesions such as LSIL-CIN 1 and HSIL-CIN 2. Higher levels of E4 protein and L1 may confirm a greater probability of the remission of lesions and incidental infections. In the cytological verification or HPV-dependent screening model, testing for E4 protein and L1 expression may indicate a group with a lower risk of progression of histopathologically diagnosed lesions.

Objectives: Long-term exposure to the human papillomavirus (HPV) is a known cause of squamous intraepithelial lesions that lead to cervical cancer. The loop electrosurgical excision procedure (LEEP) conization is an established treatment method. According to the latest recommendations, we present a paper to evaluate the effectiveness of various diagnostic methods of squamous intraepithelial lesions., Material and Methods: We analyzed 229 patients who reported to District Public Hospital in Poznan to undergo LEEP conization in 2019-2021 during the SARS-CoV-2 Pandemic. The analysis included Pap smear/liquid-based cytology, HPV genotyping, colposcopy with targeted biopsy and LEEP-conization. We offered post-treatment HPV vaccination and, as a follow-up, performed HPV re-genotyping after six months., Results: In total, 89.1% of patients were HPV-positive. The coloscopy-directed biopsy (CDB) results show that almost 70% of the patients had high-grade intraepithelial lesions (HSIL). The diagnosis obtained by LEEP-conization showed that half of the women were diagnosed with HSIL and one-third with the low-grade squamous intraepithelial lesion (LSIL). The sensitivity of Pap smear/LBC accounted for 93.7% and was lower than for CDB, which reached 95.1%. Both diagnostic methods tend to underestimate the final diagnosis., Conclusions: The inclusion of a colposcopic examination in an in-depth diagnostic process in women with abnormal Pap smear results facilitates the identification of patients requiring therapeutic intervention. LEEP-conization may be used without the primary biopsy. It applies to multiparous women in the perimenopausal period, extensive abnormalities, discrepancies in test results, extensive visible abnormalities, and suspicion of invasive cervical cancer in the colposcopic examination.

Leiomyosarcoma is one of the most common types of soft tissue sarcoma in adults, and it can occur in almost any part of the body. Uterine leiomyosarcoma constitutes 1% of all gynaecological tumours. Most diagnosed sarcomas are not even suspected before surgery. However, in recent years, awareness of their presence in society has increased. Our case aims to draw attention to the need for better cooperation between pathologists and clinicians and reduce the time from suspicion of the disease to final diagnosis.

Ovarian cancer (OC) is the eighth most common cancer worldwide and is usually diagnosed in advanced stages. The relationship between treatment in high-volume hospitals (HVHs) and survival in OC has been documented by multiple studies, which showed that superior treatment and survival outcomes are associated with surgical expertise and multidisciplinary resources. To our study, 135 first-time patients treated in the years 2019-2020 in the Department of Oncology of Poznań University of Medical Sciences were enrolled. Th analysis showed a significant dependency between being treated in a HVH from the beginning of one's diagnosis and the scope of the first intervention. Additionally, among patients treated in our centre, a significant portion of patients underwent laparoscopy, and from one year to another the number of laparoscopies performed increased. This may indicate that more patients began to qualify for neoadjuvant treatment. Patients benefit the most from surgery in a centre with more experience in treating ovarian cancer. In the future, we will be able to expand this study by using data from patients treated before 2019 and analysing larger cohorts of patients. This might enable us to update the rates of overall survival (OS), objective response rate (ORR) and progression-free survival (PFS).

Vaccinations against human papillomavirus (HPV) are included in the primary prevention of precancerous intraepithelial lesions and HPV-related cancers. Despite the undeniable effectiveness of vaccination in the juvenile population, there is still little research on the effect in patients after sexual initiation. Our study aims to assess anti-HPV (L1 HPV) antibodies in healthy patients and diagnosed cervical pathology after 9-valent vaccination. We provide a prospective, ongoing 12-month, non-randomised pilot study in which 89 subjects were enrolled. We used an enzyme-linked immunosorbent assay to determine IgG class antibodies to HPV. We noted significantly higher levels of antibodies in vaccinated individuals than in the unvaccinated control group. The above work shows that vaccination against HPV might be beneficial in patients after sexual initiation as well as in those already diagnosed with HPV or SIL infection.

Objectives: Human papillomavirus infection is one of the most common sexually transmitted infections. Histological LSIL in 70-80% of cases will regress spontaneously, while a subset is associated with residual risk for a future precancerous lesion. This study evaluates the performance of HPV genotypes for LSIL preceded by normal or mildly abnormal Pap smear., Material and Methods: We provide a prospective observational cohort study. We obtained material from 428 women registered to Specialist Medical Practice and Provincial Hospital in Poznań in 2018-2021. In the current study, we analyze results from the first 112 inclusions with the diagnosis of LSIL from a cervical biopsy. The probe for the molecular test was collected with a combi brush and passed to the independent, standardized laboratory. HPV detection was done using PCR followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe assay. Sequence analysis was performed to characterize HPV - positive samples with unknown HPV genotypes. The molecular test detected DNA of 42 HPV genotypes. We performed statistical analyzes using the STATISTICA package 13.3., Results: We found that 77.7% of patients received HPV-positive test results. The most frequent HPV genotype was 16, which was assumed for 22.3%. We detected that following HPV types are next most common: HPV 56 (11.6%), HPV 52 (8.9%), HPV 31 (8.0%) and HPV 51 (8.0%). Among HPV 16-negative women, the vast majority are those living in the town (p = 0.048). Moreover, thyroid diseases were the most common comorbidities., Conclusions: To our knowledge, this study is the most extensive assessment of HPV genotypes in LSIL diagnoses in Poland.

Objectives: Human papillomavirus infection is one of the most common sexually transmitted infections. Long-term exposure to the HPV leads to high-grade squamous intraepithelial lesions affecting cervical cancer. Knowledge about the distribution of HPV genotypes is crucial to guide the introduction of prophylactic vaccines. We aimed the genotype distribution in patients reporting due to abnormal Pap - smear tests., Material and Methods: We provide a prospective observational cohort study. We obtained material from 428 women registered to Provincial Hospital in Poznan and Specialist Medical Practice in 2018-2020. In the current study, we analyze results from the first 110 inclusions with the diagnosis of HSIL from a cervical biopsy. The probe for the molecular test was collected with a combi brush and passed to an independent, standardized laboratory. HPV detection was done using PCR followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe assay. Sequence analysis was performed to characterize HPV-positive samples with unknown HPV genotypes. The molecular test detected DNA of 41 HPV genotypes. We performed statistical analyzes using the STATISTICA package 13.3., Results: We found that 98.2% of patients received HPV-positive test results. The most frequent HPV genotype was 16, which assumed for 54.1%. In patients negative for HPV 16, the percentage decreased with increasing age. We detected that the following HPV types are next most common: HPV 31 (16.2 %), HPV 52 (11.7%), HPV 51 (9.9%), HPV 18 (9.0%), HPV 33 (9%). Moreover, thyroid diseases were the most common comorbidities and occurred in 15 patients CONCLUSIONS: To our knowledge, this study is the most extensive assessment of HPV genotypes in HSIL diagnoses in Poland.

Objectives: Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. Long-term exposure to the HPV is a known cause of squamous intraepithelial lesions that consequently lead to cervical cancer development. The loop electrosurgical excision procedure (LEEP) conization is an established early cervical cancer treatment method. We aim to assess the remission of HPV infection after LEEP in non-vaccinated patients with pre-cancerous cervical lesions and establish the efficacy of cervical cancer prophylaxis., Material and Methods: We analyzed 31 LEEP conizations performed due to low and high-grade squamous intraepithelial lesions in 2019-2020. We obtained molecular test samples and detected DNA of 37 different HPV genotypes. After a six-month follow-up, each patient underwent subsequent high-risk HPV testing and genotyping., Results: We observed that 54.8% of qualified patients were infected with HPV 16. We discovered complete viral remission in 64.5% of cases. After surgery, margins were negative in 71% of the patient's samples. During the follow-up, six patients got infected with new strains of HPV., Conclusions: We found that a correctly performed LEEP conization may contribute to the remission of persistent HPV infection; a more extended follow-up period might be recommended due to a high rate of post-surgery HPV infections.

The COVID-19 pandemic had a direct impact on the extent of guaranteed healthcare services. Many gynecologists', obstetricians', and midwives' offices were closed, laboratories suspended their activities, the collection of necessary tests was delayed, and women had to wait much longer for test results than they had to previously. General women's healthcare prophylactic programs were suspended or delayed. In 2020, screening financed by public funds covered less than one-seventh of the female population in Poland. As medical teams, professionals, clinicians, and scientists, we have been facing a challenge to help, protect, and care for one of the most vulnerable population groups, pregnant women. A significant part of that challenge has been in preventing the spread of severe COVID-19, along with other preventable diseases, among women who are pregnant, who are in labor, or who have recently given birth.

Objectives: Human papillomavirus infection is one of the most common sexually transmitted diseases. Long-term exposure to the HPV leads to development of high-grade squamous intraepithelial lesions that can eventually transform into cervical cancer. The aim of the study was to assess the HPV genotype distribution in patients with abnormal pap smear and provide prospective study., Material and Methods: We obtained material from 674 women who registered to Specialist Medical Practice in the years 2008-2020. The sample for the molecular test was collected using combi brush and forwarded to the independent, standardized laboratory. HPV detection was done using PCR followed by DNA enzyme immunoassay and reverse hybridization line probe assay for virus genotyping. Sequence analysis was performed to characterize virus genotypes in HPV - positive samples., Results: We found that 53% of patients tested positive for HPV. The percentage decreased with age. The following HPV types were the most common: HPV - 16 (24.5%), HPV - 53 (13.1%), HPV - 31 (10.3%), HPV - 51 (9.7%), HPV - 56 (9.5%). To our knowledge, this study is the largest assessment of HPV genotypes in Poland., Conclusions: Our results suggest that type-specific, high-risk HPV DNA - based screening should focus on HPV types 16, 31, 51, 56.

Objectives: The paper assess the relevance of HR HPV E6/E7 mRNA test in women with abnormal Pap results., Material and Methods: Between 2013-2014, 125 women were subjects to the enhanced diagnostics due to abnormal Pap results. According to The Bethesda system, if ASC-US, AGC, LSIL, ASC-H, HSIL or cancer cells were present, the result was abnormal. The patients underwent the enhanced diagnostics which included the following procedures: Pap smear collection for molecular assessment of HR HPV E6/E7 mRNA test, the colposcopic examination and biopsy of clinically suspicious areas., Results: High-grade squamous intraepithelial lesions constituted the most frequent cervical pathology in women with abnormal Pap test results, as well as with the positive results of HR HPV E6/E7 mRNA test. Test sensitivity in patients with the histopathological diagnosis of high-grade squamous intraepithelial lesion was estimated at 86.1%., Conclusions: HR HPV E6/E7 mRNA test identifying neoplastic lesions and cervical cancer is characterised by a high relevance which is reflected by means of sensitivity and specificity. In fact, test sensitivity and specificity increased with the age in the group of patients up to 50 years old.

Objectives: To assess the incidence of cervical intraepithelial neoplasia - SIL and cervical cancer in a population of pregnant women with an abnormal cytology., Material and Methods: In pregnant women with abnormal cytology results according to The Bethesda System, a verifying diagnostics was carried out, including colposcopy and cervical biopsy., Results: The most common histological and oncologic diagnosis in the whole study group of pregnant women were HGSIL changes, covering cervical intraepithelial neoplasia of medium and high grade - CIN 2 and CIN 3., Conclusions: HGSIL changes are the most common oncological pathology in a population of pregnant women with an abnormal cytology. Precise risk identification of HGSIL changes with the use of molecular tests can significantly reduce the number of surgical procedures in a population of pregnant patients with a cytological diagnosis of ASCUS and LSIL.

Objectives: To assess the diagnostic value of cervical cytology and HPV HR DNA testing for the diagnosis of low grade and high-grade squamous intraepithelial lesions across different age groups., Material and Methods: The study included 1103 patients, age 25-70 years. All patients underwent in-depth diagnostic tests following either an abnormal Pap test result or a clinically suspicious cervical lesion. In all women the following examinations were performed: a molecular test detecting 14 high-risk types of HPV, a colposcopy examination, as well as directed-biopsy of the cervix. The studied population was subdivided into four age groups., Results: It was observed that the percentage of high grade squamous intraepithelial lesions (HSIL) and cancers increased with women's age. Sensitivity of both methods for detecting high-grade squamous intraepithelial lesions was highest for women aged 40-49 years. Sensitivity values of HPV testing was higher than that of cervical cytology among women under age 50., Conclusions: Specificity of HPV testing increased significantly with age of women and was several fold higher across all age groups than the specificity of cervical cytology.

Objectives: The aim of this work is to evaluate levels of placental growth hormone (PGH), pituitary growth hormone (GH1), insulin-like growth factor (IGF-I) and ghrelin in pregnant women's blood serum before, during and after delivery. Furthermore, the aim is to search for links and interdependence of GH1, PGH and IGF-I concentrations., Material and Methods: Seventy nine blood samples were taken one to two hours before, during and half an hour after expulsion of placenta. All proteins studied were determined by ELISA method, using ELISA Kit., Results: The highest PGH concentration and IGF-I concentration in pregnant women's blood serum was observed before delivery while GH1 concentration was lowest. During and after delivery PGH and IGF-I concentration decreased proportionately and pituitary growth hormone concentration increased accordingly. About half an hour after delivery of the placenta, GH1 concentration was highest., Conclusions: In pregnant women's blood there is a metabolic interdependence between PGH and IGF-I. Their concentration increases proportionately during pregnancy and decreases after delivery. It appears that labor and delivery releases GH1 blockade, which level rises three-fold during delivery. After parturition its role and concentration returns to levels before pregnancy.

Aim of the Paper: Comparison of conventional cytodiagnostics with molecular identification of DNA and mRNA HPV HR, immunocytochemical test for suppressor protein P16 and nuclear Ki 67 to detect cervical pathology screening of the division to LG SIL and HG SIL., Material: 630 Pap smears were taken from women with suspected cervical pathology were submitted for analysis, together with 558 smears for the presence of DNA HPV HR, 421 swabs for the presence of mRNA HPV HR, 86 swabs for the presence of suppressor protein P16 and nuclear Ki 67. In all of the women standard colposcopy with biopsy and endocervical abrasion were performed., Method: The study used a classic cytological smear taken on the slide, rated in accordance with TBS classification, colposcopy implemented in accordance with the guidelines of the International Federation of Cervical Pathology and Colposcopy from 2003, molecular diagnostic tests based on identifying DNA, mRNA HPV HR and immunocytochemistry diagnostic test--CINtecPLUS., Results: The sensitivity of Pap test identification of CIN 2+ was of 85% and specificity of 23%. Indicators PPV and NPV were respectively 39% and 72%. The accuracy of cytology reached a level of 46%. DNA HPV HR test obtained 91% sensitivity and 33% specificity of the diagnosis of CIN 2+. Its accuracy was 54%. The value of PPV and NPV for molecular diagnostics was respectively 43% and 87%. For mRNA HPV HR test sensitivity of the method was 79%, the specificity was 67%. CINTecPLUS test achieved 100% sensitivity and 67% specificity in the diagnosis of CIN 2+., Conclusions: 1. Conventional cytodiagnostics are inferior in terms of both sensitivity and specificity of molecular test for DNA, mRNA HPV HR and immunocytochemical test for detecting of LG SIL and HG SIL. 2. Immunocytochemical technique shows maximum sensitivity and high specificity of detection of actual precancerous stages--CIN 2+.

Objectives: Assessment of frequency of regression and progression of mild cervical neoplasia in women positive for types of HPV DNA of high oncogenic potential., Materials and Methods: 111 women were studied. One-year-long observation of patients included cervical cytology conducted every three months, and colposcopy conducted every six months. After a period of 12 months all women were evaluated with colposcopy and directed biopsies of abnormal cervical tissue., Results: This study confirms the significant effect of age on both regression and progression of low-grade cervical intraepithelial neoplasia., Conclusions: In the age group below 26 years, complete regression of LGSIL occurs significantly more frequently than in older women. Whereas in the over 36 age group, progression to HGSIL occurred more frequently during 12 months of follow-up.

To search for favourable prognostic factors in carcinosarcoma (CS) on the basis of clinical, morphological and immunocytochemical data, while simultaneously considering the histogenesis of this neoplasm. Thirty two uterine CS patients were analysed based on clinical and morphological data. In addition, each specimen was examined by immunohistochemistry with antibodies characteristic for relevant types of cells and tissues. The presence of both carcinomatous and sarcomatous patterns was observed in all tumours. Among carcinomatous patterns, endometrioid carcinoma was the commonest, while serous, clear cell, and undifferentiated carcinomas were less common. Among sarcomatous patterns, endometrioid sarcomas represented the largest group, while leiomyosarcomas, chondrosarcomas, fibrosarcomas, osteosarcomas, and rhabdosarcomas were rarely observed. Mitotic activity was evidently higher in carcinomas. In seven cases, the expression of both cytokeratin and vimentin was noted in cells of carcinomatous patterns. We found that an early diagnosis (stage I-II) and an initially aggressive surgical cytoreduction were favourable prognostic factors in CS. Furthermore, the presence of cytokeratin-vimentin positive cells in carcinomatous patterns suggests sarcomatous metaplasia of adenocarcinoma. However, the prognostic value of various histological structures of carcinosarcomas could not be identified.

Introduction: Development of primary prevention of cervical cancer in other words a vaccination against selected, oncogenic HPV types, entails an increasing importance of epidemiological studies and prevalence of various types of human papilloma virus. The incidence of HPV varies depending on the geographic location of the population. The effectiveness of primary prevention against HPV 16, 18, in the context of reducing the incidence of cervical cancer will depend, among others, on the prevalence of these types in the population and virus-like antigens, which are partially cross-resistant., Objective: Identification of the most frequent, oncogenic HPV types in women with HG SIL diagnosis from Central and Western Poland to assess the merits of the development of primary prevention., Material: For the purpose of molecular tests identifying the presence of 13 DNA oncogenic virus types, swabs were taken with the cyto-brush from 76 women diagnosed with CIN 2 or CIN 3 (HG SIL). Patients eligible for the study were diagnosed at the Laboratory of Pathophysiology of Uterine Cervix, Gynecology and Obstetrics Clinical Hospital of Karol Marcinkowski University of Medical Sciences. Patients came from Central and Western parts of Poland., Method: Cell material in which the method of Amplicor HPV (Roche Diagnostics) identified the presence of DNA of oncogenic HPV types was in each case subsequently subjected to genotyping using the molecular test - Linear Array HPV Genotyping (Roche Diagnostics)., Results: Five most common oncogenic HPV types in order of detection included: 16, 33, 18, 31, 56. Together these five types of virus comprised 75.86% (88/116) of all detected HPV types., Conclusions: 1. In women from Central and Western Poland, diagnosed with HG SIL, the most common HPV genotypes were HPV 16, HPV33, HPV 18, HPV31, HPV56. 2. Two HPV types 16 and 18, against which vaccinations are directed, belong to the group of three genotypes of HPV most commonly identified in the evolution of CIN 2, CIN 3 diagnosed in women from Central and Western Poland.

Introduction: Cervical cancer remains a considerable diagnostic and therapeutic problem in Poland. Despite progress in creating an active cancer prevention program in our country Poland occupies one of the last places in the EU in terms of cervical cancer- morbidity and mortality Supplement of secondary prevention of primary prophylaxis-HPV 16, 18 vaccination, offers hope for improvement of the situation. Epidemiology of individual HPV types differs, depending on the geographical location of the study population. So far in Poland, we have had no reliable data on the participation of selected oncogenic HPV types in the development of cervical pathology, Objective: Identification of the most frequent, oncogenic HPV types in women diagnosed with CIN 1, from the Central and Western Poland., Material: In the course of the conducted studies, genotyping of 13 types of human papilloma virus has been done in 126 HPV DNA-positive women diagnosed with CIN 1., Method: Each cell material in which the presence of HPVDNA identified 13 types of oncogenic human papillomavirus was subsequently subjected to genotyping using the molecular test--Linear Array HPV Genotyping (Roche Diagnostics)., Results and Conclusion: In women from the Central and Western Poland diagnosed with CIN 1, HPV 16 (53.97%) was the most common, followed by HPV 33 (21.3%), HPV 18 (16.67%), HPV 31 (10.32%), HPV 45 (7.94%), HPV 52 (1.59%). Current HPV vaccines are designed to protect against two of the three most common genotypes, in women diagnosed with CIN 1 in Central and Western Poland.

Introduction: Biophysics and molecular biology are disciplines dynamically entering the area of cervical cancer prevention. The combined test, comprising optoelectronic and molecular diagnostics, may play a significant role in the decrease of cervical cancer incidence and mortality., Objective: Assessment of the combined test usefulness--optoelectronic method and HPV test for the presence of oncogenic HPV types, in the detection of cervical intraepithelial neoplasia and cervical cancer., Material and Method: From August 2006 to October 2008 the study included 250 patients from the Laboratory of Pathophysiology of Uterine Cervix in Gynecology and Obstetrics Clinical Hospital of Karol Marcinkowski University of Medical Sciences. The patients underwent the following diagnostic tests: optoelectronic method, PCR test for the presence of DNA HPV HR, colposcopic examination and histopathologic biopsy., Results: Sensitivity of the combined test for low-grade intraepithelial changes in the area of squamous epithelium (CIN 1) was 81%, while for high-grade changes (CIN 2, CIN 3) and carcinoma planoepitheliale together with adenocarcinoma was 100%., Conclusions: Optoelectronic and molecular diagnostics methods are useful in detecting neoplastic cervical changes. Both methods may become a key diagnostic tool of basic and advanced level of cervical screening. The advantage of the combined optoelectronic method and molecular diagnostics method over prevention based on cytodiagnostics and colposcopy has its source in the possibility of test automation and standardization.

Coincidence of preinvasive vulvar and cervical cancer in young women is very rare. Lesions like VIN 3/preinvasive vulvar cancer and CIN 3/preinvasive cervical cancer are strictly connected with viral infection and are multilocular. In the presented case the following tests have been performed: HPV DNA test for the presence of 13 oncogenic HPV types, mRNA HPV test for the presence of transcripts for HPV 16, 18, 31, 33, 45 and the analysis of mtDNA D-Loop region. In the examined patient HPV 16 infection, as well as the presence of transcripts for HPV 16 E6/7 were diagnosed. The analysis of mtDNA D-Loop region showed nucleotide lesions like: T>C 16.192, T>C 16.223, T>C 16.292, C>T 16.325, C>T 16.579.

Introduction: During pregnancy viruses of high oncogenic potential--types 16, 18, 31, 33, 35, which had so far remained in the state of chronic infection, undergo reactivation. Among the potential ways of HPV transmission to foetus, the direct perinatal infection is mentioned. In the antenatal period of pregnancy, a descending way of infection through blood is analyzed., Objectives: The purpose of this study is to evaluate the risk factors and frequency of occurrence of HPV DNA of high oncogenic types in paraepidermal epithelium cells of the uterine cervix, in the trophoblast, and in the peripheral blood of pregnant patients., Material and Methods: The research included 185 pregnant women hospitalized in the Delivery Room, of the Gynecological and Obstetric Clinic of the Poznan Medical University, in years 2005-2006. All patients who took part in the research had been interviewed prior to delivery with the help of a pre-designed questionnaire. Samples of cellular material from the cervix were collected before the delivery (185 specimens). 4-5 ml of peripheral blood (103 specimens) were collected as well. The collection of the cellular material was performed with the use of Cervex-Brush. Samples of tissue from placenta (138 specimens, including 5 pairs of twins) were collected after delivery., Results: The research concludes, that incidental or chronic infection evoked by HPV HR presence in paraepidermal epithelium cells of the uterine cervix has been observed in nearly 30% of pregnant women. The presence of HPV HR DNA in the placenta cells of the HPV HR positive mothers applies to less than 6,5% of the researched women. Identification of the genetic material of Papillomavirus in peripheral blood of pregnant women indicates that this occurrence is incidental. The analysis of the risk factor of the development of HPV infection has exerted that the positive result of molecular tests on the presence of HPV HR DNA concerns the population of young women from 18 to 30 years of age., Conclusions: Incidental or persistent infection with highly oncogenic types of HPV present in cervix paraepidermal epithelium cells is observed in approximately 30% of pregnant women. The presence of DNA HPV HR in trophoblast cells of HPV HR positive mothers is diagnosed rarely, in less than 7% of pregnant women. Human Papilloma Virus is present in the peripheral blood of pregnant women sporadically. None of the currently known risk factors of HPV infection may be correlated with DNA HPV HR presence in pregnant women.

Introduction: Diagnostic algorithm for women with ASC-US presumes the possibility of performing molecular test for DNA HPV HR, colposcopy or repeated cytology. The latest suggestions of diagnostic algorithm modification in case of cytologic interpretation of LSIL, are based on trial of performing molecular DNA HPV HR test and/or genotyping human papilloma viruses with the special indication for type 16. These suggestions presume performing colposcopy in women with DNA HPV HR or DNA HPV 16 (+)., Material and Method: Triage study included 67 women with ASC-US and 48 women with LSIL. All 115 women were examined with the use of molecular test Amplicor HPV Roche Diagnostics, which identifies the presence of any out of 13 oncogenic DNA HPV types. 14 women with LSIL DNA HPV HR (+) interpretation, were additionally tested for identification of HPV genotypes presence. In all women with cytologic evidence of ASC-US and LSIL, a colposcopic examination was further performed., Results: Among 67 examined women with ASC-US interpretation, 31 had a (+) test for the presence of any out of 13 HPV HR, while in 12 patients, the result of pathomorphological examination confirmed at least the presence of CIN 1. In none of 36 patients with ASC-US, DNA HPV HR (-) interpretation, the presence of CIN was confirmed. For 29 women with LSIL, (+) test result for any out of 13 HPV HR was obtained. In 117 patients OUT of this group, at least the presence of CIN 1 was recognized. Following 19 women with LSIL had a negative test result for DNA HPV HR. In none of the patients with DNA HPV HR (-), the presence of CIN was confirmed. DNA HPV 16 was recognized in 5/9 patients with LSIL, without CIN. In 5 patients with LSIL, who underwent HPV genotyping, and were diagnosed for CIN, 4/5 were DNA HPV 76 (+). The most common HPV types in women with LSIL and the presence of CIN include; HPV 16 and HPV 37., Conclusions: 1. Negative DNA HPV HR result, identifies precisely women with ASC-US and LSIL, without CIN. 2. Genotyping exclusively DNA HPV 16 in women with LSIL, in order to detect CIN is characterized by lower sensitivity and specificity in comparison with universal test for 13 oncogenic HPV types.

Introduction: Biophysics is becoming an important factor in prevention of cervical cancer. One of the most promising concepts of biophysical program for the prevention of cervical cancer is the optoelectronic method--Truscreen., Objective: The objective of the work was to determine the usefulness of the real optoelectronic device in the detection of cervical intraepithelial neoplasia, Material and Method: From August 2006 till September 2007, 147 patients were examined in the Laboratory of Pathophysiology of Uterine Cervix in Gynecology and Obstetrics Clinical Hospital of Karol Marcinkowski University of Medical Sciences. The study reports prospective, blind trial. The following diagnostic examinations were carried out: examination with the use of optoelectronic method, DNA HPV HIGH RISK test, colposcopy examination and histopatologic biopsy., Results: The specificity of the optoelectronic method for positive diagnoses amounted to 84%. The sensitivity for intraephitelial changes (CIN 1, CIN 2) was estimated at 53%, and for severe grades (CIN 3, Carcinoma planoepitheliale) at 80%., Conclusions: Optoelectronic diagnostics is useful in the detection of cervical neoplastic changes. The optoelectronic method may prove to be a significant diagnostic device at the basic and advanced level of cervical screening. The advantage of the optoelectronic method over prevention based on cytodiagnostics and colposcopy, includes the immediate result of the examination and its automation as well as standardization.

Melanin synthesis of follicular melanocytes is strictly coupled to the growth stage of the hair cycle (anagen), ceases during follicle regression (catagen), and is absent throughout the resting stage (telogen). Having previously characterized the expression and activity of melanogenesis-related proteins during the telogen-anagen transition of the murine hair cycle (JID 96:172, 1991), we here report a biophysical and biochemical analysis of follicular melanogenesis during the anagen-catagen-telogen transformation of the C57 BL-6 mouse hair cycle. Tyrosinase activity and concentration as well as dopachrome tautomerase activity were compared with melanin synthesis, as measured by electron paramagnetic resonance spectroscopy (EPR). The visible changes in skin color and the histologically appreciable switch-off of melanin formation during the anagen-catagen transformation were accompanied by a steep decline in 1) the melanin-associated EPR signal of full-thickness mouse skin, 2) tyrosinase and dopachrome tautomerase activities, and 3) the skin concentration of 80-85-kD melanogenesis related protein and 66-68-kD tyrosinase protein. Telogen skin displayed a minimum of the EPR amplitude as well as of tyrosinase and dopachrome tautomerase activity detected. By EPR, only eumelanin was identified during all hair cycle stages. The gradual switch-off of melanogenesis during anagen VI started with an unexpectedly early decline of the EPR melanin signal, followed by dopachrome tautomerase activity and the concentration of 80-85-kD melanogenesis related protein. The initiation of catagen was characterized by a significant and rapid decrease in activity and concentration of tyrosinase, and was accompanied by a second drop in dopachrome tautomerase activity. Together, these biochemical and biophysical parameters of follicular melanogenesis serve as novel and differential markers for the imminent termination of anagen and the development of catagen. They also show that the switch-off of melanogenesis during the anagen-catagen-telogen transition is a stochastic process commencing already in mid anagen VI.

Arylamine N-acetyltransferase (EC 2.3.1.5) activity was examined using skin from Syrian hamster. Two isozymes of arylamine N-acetyltransferase, designated NAT-1 and NAT-2, were detected on anion-exchange high-performance liquid chromatography analysis. Both enzyme activities had indistinguishable molecular masses (30 kDa), but differed significantly in their specificity toward the aromatic amines including serotonin, dopamine, methoxytryptamine, tryptamine, para-phenetidine, para-aminobenzoic acid, and sulphamethazine. Specifically, NAT-2 but not NAT-1 catalyzed acetylation of dopamine to N-acetyldopamine and acetylation of serotonin to form N-acetylserotonin, a direct precursor of melatonin. The two isozymes were also distinguishable based upon their sensitivity toward methotrexate inhibition (50% inhibiting dose for NAT-1 = 380 microM; NAT-2 > 2 mM). The presence of these two activities in the skin raises new questions about the physiologic role of this enzyme in general and in the skin-specific functions in particular.

The effects of melatonin on proliferation and on the induction of melanogenesis in rodent melanoma cells were investigated. It was found that melatonin at low concentrations (0.1-10 nM) inhibited cell growth but had no effect on melanogenesis, while at high concentrations (> or = 0.1 microM) it inhibited the induction of melanogenesis but not cell growth. These effects were specific since corresponding concentrations of the direct precursor and product of melatonin degradation N-acetylserotonin (N-Ac-5HT) and 5-methoxytryptamine (5MT), respectively, did not have any effect on cell proliferation or melanogenesis. At very high concentration (100 microM) both N-Ac-5HT and melatonin could stimulate melanoma proliferation while 5MT inhibited it. The demonstration of differential and unparalleled effects of melatonin on cell proliferation and melanogenesis suggests that melatonin can regulate or modify both processes via different mechanisms.

Rapid, saturable, specific and stereoselective binding of L-dopa to crude membranes and purified nuclei from rodent amelanotic melanoma cells is reported. Cross-linking of [3H]dopa to melanoma cell surface emphasized proteins of approx. 55, 30, 25 and less than 20 kDa. It is suggested that these binding sites may regulate melanocyte activity.