Normal Cytology Results Research Articles

Evidence of Decreased Long-term Risk of Cervical Precancer after Negative Primary HPV Screens Compared with Negative Cytology Screens in a Longitudinal Cohort Study.

The growing use of primary human papillomavirus (HPV) cervical cancer screening requires determining appropriate screening intervals to avoid overtreatment of transient disease. This study examined the long-term risk of cervical precancer after HPV screening to inform screening interval recommendations. This longitudinal cohort study (British Columbia, Canada, 2008 to 2022) recruited women and individuals with a cervix who received 1 to 2 negative HPV screens (HPV1 cohort, N = 5,546; HPV2 cohort, N = 6,624) during a randomized trial and women and individuals with a cervix with 1 to 2 normal cytology results (BCS1 cohort, N = 782,297; BCS2 cohort, N = 673,778) extracted from the provincial screening registry. All participants were followed through the registry for 14 years. Long-term risk of cervical precancer or worse [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)] was compared between HPV and cytology cohorts. Cumulative risks of CIN2+ were 3.2/1,000 [95% confidence interval (CI), 1.6-4.7] in HPV1 and 2.7/1,000 (95% CI, 1.2-4.2) in HPV2 after 8 years. This was comparable with the risk in the cytology cohorts after 3 years [BCS1: 3.3/1,000 (95% CI, 3.1-3.4); BCS2: 2.5/1,000 (95% CI, 2.4-2.6)]. The cumulative risk of CIN2+ after 10 years was low in the HPV cohorts [HPV1: 4.7/1,000 (95% CI, 2.6-6.7); HPV2: 3.9 (95% CI, 1.1-6.6)]. Risk of CIN2+ 8 years after a negative screen in the HPV cohorts was comparable with risk after 3 years in the cytology cohorts (the benchmark for acceptable risk). These findings suggest that primary HPV screening intervals could be extended beyond the current 5-year recommendation, potentially reducing barriers to screening.

Фототераностика тяжелых дисплазий и преинвазивного рака шейки матки

Due to the high prevalence of pre-cancerous cervical diseases and cervical cancer, the search, pathogenetic reasoning and evaluation of the efficacy of new approaches to the diagnosis and treatment of these pathologies, including those aimed at fertility preservation, are extremely relevant. Objective. To study the clinical efficacy and safety of phototheranostics as a method of diagnosis and treatment of severe dysplasia and pre-invasive cervical cancer. Patients and methods. An open-label, retrospective-prospective, randomized, comparative, clinical trial involving 94 reproductive-aged patients with morphologically confirmed severe cervical intraepithelial neoplasia (CIN) and pre-invasive cervical cancer was conducted. All patients were divided into two groups: group 1 (comparison) included 49 patients who underwent cervical conization with curettage of the remaining cervical canal; group 2 (study) included 45 patients who underwent phototheranostics: photodynamic therapy (PDT) with simultaneous laser-induced fluorescence excitation. Results. After the first course of phototheranostics, most women in the study group had normal cytological results, which were observed 6, 9, and 12 months after treatment. In these periods, all patients who underwent phototheranostics had a normal colposcopic picture, while in the comparison group, some patients showed signs of cervical lesions. Morphological confirmation of the complete therapeutic effect was considered to be elimination of human papillomavirus (HPV) and normalization of the proliferative activity of the epithelial layer (assessed by the levels of Ki-67 and phosphohistone markers) during phototheranostics. Conclusion. The study demonstrated the high clinical efficacy of phototheranostics in the treatment of CIN and pre-invasive cervical cancer: 85–88% of women achieved the desired therapeutic effect after the first session of phototheranostics, and after the second session, all patients in the study group had complete regression of cervical mucosal lesions. In the study group, higher pregnancy rates and favourable outcomes in patients planning pregnancy confirmed that the use of PDT contributes to fertility preservation in women treated for CIN and pre-invasive cervical cancer, which is associated with the preservation of anatomo-functional characteristics of the cervix when using phototheranostics. Key words: PDT, HPV, photodynamic therapy, fluorescence diagnosis, cervical dysplasia, photosensitizers, pre-invasive cervical cancer, phototheranostics, pregnancy after PDT

Prevalence and genotype screening of human papillomavirus among women attending a private hospital in Northern Cyprus: an 11-year retrospective study

BackgroundHuman papillomavirus (HPV) is the most common sexually transmitted pathogen both in men and women. Accumulating epidemiological evidence supports a strong association between HPV infection and cancer of the cervix, vulva, vagina, anus, and penis. Currently, data on the HPV prevalence and genotyping is lacking in Northern Cyprus, a region in which HPV vaccination is not freely accessible via the national immunization program. The aim of this study was to evaluate the HPV type-specific prevalence in women with and without cytological abnormalities living in Northern Cyprus.MethodsA total of 885 women who presented to the Department of Gynecology and Obstetrics Clinic between January 2011 and December 2022 were included in the study. Samples were collected for cytology. Cervical specimens were investigated for the presence of HPV-DNA and genotyping of HPV was performed using real-time polymerase chain reaction (rtPCR). Cytological examination was interpreted according to the Bethesda system.ResultsAmong all patients, overall high-risk HPV DNA prevalence was 44.3%. HPV-16 and HPV-18 positivity was found in 10.4% and 3.7% of women respectively, while other high-risk HPV (OHR-HPV) was the most frequent type of HPV (30.2%). The highest frequency of HPV infection was observed in the 30–55 age group (51.0%), followed by the < 30 age group (45.7%). Co-infection with two or more HPV types was observed in 17.0% of all positive samples, in which the prevalence of HPV-16 + HPV-18 was 2.3%, HPV-16 + OHR-HPV and HPV-18 + OHR-HPV was 12.0% and 5.1%, respectively. Among the screened patients, 37.5% had abnormal and 62.5% had normal cytology results. HR-HPV positivity was 65.7% and 34.0% in patients with abnormal and normal cytology. The highest incidence of HRC-HPV was OHR-HPV types (44.7%) in positive cytology cases. Among women with a cytology result of ASCUS, L-SIL, H-SIL and unspecified dysplasia, 52.1%, 67.6%, 97.5% and 75.6% were respectively infected with HR-HPV.ConclusionThe present study provides the latest epidemiological data related to HPV prevalence and genotype distribution among women living in Northern Cyprus. Considering the unavailability of free vaccination in the community, it is imperative to implement local HPV screening programs and provide guidelines on HPV prevention and measures during early school education.

Comparison of the Clinical Performance of Aptima HPV Assay and the Cobas 4800 Platform in Women with Normal Cytology and Positive High-Risk HPV

Introduction: According to the current American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines, patients with normal cytology results may be referred for colposcopy according to their high-risk human papillomavirus (hrHPV) test results. A higher positive predictive value (PPV) of hrHPV has significance for preventing unnecessary colposcopic examinations. Several studies have compared the performance of the Aptima assay and the Cobas 4800 platform among patients who had minor cytologic abnormalities. However, in our English literature search, we found no other study that had been conducted to compare these two methods in patients with normal cytology. We thus aimed to compare the PPV of the Aptima assay and the Cobas 4800 platform among women with normal cytology. Methods: Between September 2017 and October 2022, we retrospectively identified 2,919 patients who had normal cytology and hrHPV positivity and had been referred for a colposcopy. Among them, 882 agreed to undergo a colposcopy; on examination, 134 had target lesions revealed and underwent a colposcopic punch biopsy. Results: Among the patients who underwent a colposcopic punch biopsy, 49 (38.9%) were tested with Aptima, and 77 (61.1%) were tested with Cobas. In the Aptima group, 29 (59.2%) patients showed benign histology, 2 (4.1%) patients had low-grade squamous intraepithelial lesions (LSILs), and 18 (36.7%) patients had ≥high-grade squamous intraepithelial lesions (HSILs) biopsy results. The false-positivity rate and PPV of Aptima were 63.3% (31/49) and 36.7% (95% confidence interval [CI]: 0.232–0.502), respectively, for a histopathologic diagnosis of ≥HSIL. In the Cobas group, 48 (62.3%) biopsies were benign, 11 (14.3%) reported an LSIL, and 18 (23.4%) biopsies were ≥HSIL. The false-positivity rate and PPV of Cobas were 76.6% (59/77) and 23.4% (95% CI: 0.139–0.328), respectively, concerning a ≥HSIL tissue diagnosis. The false-positivity rate of Aptima HPV 16 positivity was 40% (4/10). The false-positivity rate of Cobas HPV 16 positivity was 61.1% (11/18). The PPVs of HPV 16 positivity for Aptima and Cobas were 60% (95% CI: 0.296–0.903) and 38.9% (95% CI: 0.163–0.614), respectively, concerning ≥HSIL tissue diagnosis. Conclusion: We recommend analyzing the performances of hrHPV platforms in future, larger studies in patients with normal cytology rather than only in cases with abnormal cytology.

What is the effect of vitamin D deficiency on Pap smear test results in the postmenopausal period?

This study aimed to determine the impact of vitamin D deficiency on Pap smear test results in women in the postmenopausal period. This cross-sectional study included 394 women who applied to İstanbul Medeniyet University, Göztepe Training and Research Hospital gynecology and obstetric clinic for routine Pap smear tests. This study was conducted between May 2019 and December 2020. Cases were divided into severe deficiency (&lt;12 ng/ml), moderate deficiency (12-20 ng/ml), deficiency (21-30 ng/ml), and sufficiency (&gt;30 ng/ml) according to the vitamin D levels measured in the postmenopausal period within the scope of check-up examinations. Pap smear test results compared with vitamin D levels. The mean age of the study group was 48.70±3.46 years. There was a statistically significant association between vitamin D values and Pap smear test results (p&lt;0.05). Vitamin D greater than 20 ng/ml had a significant relationship with the normal cytology results. There was a statistically significant association between vitamin D lower than 20 ng/ml and cervicitis cytology results. The results showed that the serum vitamin D and the Pap smear test results had a significant association. It is recommended that physicians prescribe the use of vitamin D supplements in women in the high-risk group of cervical cancer.

Geotropism and oncogenic potential of HPV infections in cohort study populations in Vojvodina, North region of Serbia

Background/Aim: Geotropism of the human papillomavirus (HPV) represents the heterogeneous distribution of different genotypes worldwide. Aim of this study was to evaluate the prevalence of the HPV infection in women from Vojvodina, Serbia, according to cytological status and pathological changes of cervix - dysplasia and cancer. Methods: The research was conducted as a retrospective study at the Oncology Institute of Vojvodina and the Institute of Public Health of Vojvodina (IPHV). Data from the medical records of female patients treated for cervical intraepithelial neoplasia or cervical cancer at the Department of Gynaecology, Clinic for Surgical Oncology, Oncology Institute of Vojvodina in Sremska Kamenica in the period from 2016 to 2021 were used, as well as the laboratory findings of the IPHV for a group of patients with normal cytological results of the Papanikolau (PAPA) smear. Results: A total of 731 women, from 20 to 82 years of age, with different cytological results were enrolled. 567 samples were classified as NILM, while 164 samples belong to a group of abnormal histopathology (LSIL/HSIL/cervical cancer). The HPV genotyping assay was performed using the EUROArray HPV test to detect 30 HPV genotypes. In the overall number with normal cytological findings, HPV infection was verified in 242 (42.7 %) patients, of which 135 (55.8 %) were verified with high risk HPV, while 76 (31.4 %) were verified with a mixed group of HPV (Low risk/High risk HPV). Most prevalent genotypes were HPV 16, 31, 53, 51 and 18 in NILM cytological status. In the samples with the abnormal histopathology, the most prevalent genotypes were HPV 16, 33, 31 and 56, while 18 and 39 were equally verified. Genotype 16 was the most prevalent in the examined sample, with a higher prevalence in higher-grade histopathological findings: 18.8 % in LSIL, 31.9 % in HSIL and 75.0 % in cervical cancer samples. Infection with multiple associated genotypes of HPV was not correlated with histopathology. By comparing histopathological diagnosis and age, older patients had higher-grade lesions. Conclusion: Based on the estimated oncogenic potential of HPV genotypes as well as their prevalence in presented sample, it can be concluded that the nine-valent HPV vaccine for genotypes 6, 11, 16, 18, 31, 33, 45, 52 and 58 would have the potential to prevent HPV infection and the incidence of precancerous lesions and cervical cancer in about 85 % of women. Observing trends in the prevalence of HPV, especially HR HPV genotypes, can be important in the further strategy of applying secondary and primary prevention, as well as the application of HPV detection as part of co-testing or considering the introduction of HPV testing in the initial screening program.

Impact of HPV mRNA types 16, 18, 45 detection on the risk of CIN3+ in young women with normal cervical cytology.

Despite a well-established cervical cancer (CC) screening program in Norway, the incidence of CC in young women is increasing, peaking at 35 years of age. 25 percent of all women diagnosed with CC had normal cytology within 3 years prior to cancer diagnosis, addressing the need to improve the screening programme to further reduce cancer incidences missed by cytology. We wanted to investigate the detection rate of CIN3+ in women 25-39 years with normal cytology by using a 3-type HPV mRNA test as a targeted quality assurance measure. The control group is women with normal cytology. During 2014-2017, samples from 13,021 women 25-39 years of age attending cervical cancer screening were analysed at Nordlandssykehuset, Bodø, Norway, including 1,896 women with normal cytology and HPV mRNA test (intervention group), and 11,125 women with cytology only (control group). The HPV mRNA testing was performed using a 3-type HPV E6/E7 mRNA test (PreTect SEE; direct genotyping 16, 18 and 45). The women were followed-up according to national guidelines throughout December 2021. Of the 13,021 women, 429 women (3.3%) had CIN3+ confirmed by biopsy in the follow-up, including 13 cases of invasive cervical cancer. Of the 1,896 women with normal cytology and HPV mRNA test (intervention group), 49 women (2.6%) had a positive test. The risks of CIN3+ among women with either a positive or negative HPV mRNA test were 28.6% (14/49) and 0.8% (14/1847). None of the women in the intervention group developed cervical cancer during follow-up. Of the 11,125 women with cytology only (control group), 712 women (6.4%) had abnormal cytology (ASC-US+). The risks of CIN3+ among women with abnormal and normal cytology were 17.7% (126/712) and 2.6% (275/10,413). By testing women 25-39 years of age with a normal cytology result using a specific 3-type HPV mRNA test, an increase in screening programme sensitivity can be achieved without an excessive additional workload. Women with normal cytology and a negative HPV mRNA test have a very low risk of cervical cancer.

Anti–Gamma Aminobutyric Acid B Autoimmune Encephalitis in an Indian Child with Early-Onset Seizures, Neurodegeneration, and Brain Calcification due to NRROS Variation: The First Reported Case Worldwide

AbstractA 1.5-year-old boy presented to us with a history of normal growth and developmental parameters until 6 months of age. However, at 7 months of age, he developed multiple types of seizures consisting initially of complex febrile seizures, followed by afebrile seizures. Multifocal clonic, generalized tonic–clonic, and myoclonic (multifocal and generalized) were the evolving seizure types. He had truncal hypotonia, but his appendicular hypotonia progressed to hypertonia over the next few months and further to decorticate posturing. Brain magnetic resonance imaging (MRI) showed generalized atrophy, predominantly frontotemporal, without any focal signal abnormalities or contrast enhancement. Computed tomography (CT) showed speckled calcification in subcortical white matter. Electroencephalogram showed bilateral frontotemporal epileptiform discharges with secondary generalization. His cerebrospinal fluid had normal cytology and biochemical results but was positive for anti–gamma aminobutyric acid B antibodies. Whole exome sequencing showed likely pathogenic, novel autosomal recessive homozygous variation of NRROS gene on chromosome 3 [c.1487G &gt; A (p.Trp496Ter)], which impairs the functioning of anti-inflammatory cytokine transforming growth factor beta, resulting in a proinflammatory state within the central nervous system and thereby promoting autoimmune encephalitis. Parental Sanger sequencing validated the variation in both his parents. He was treated with both pulse methylprednisolone (30 mg/kg/day for 5 days) and intravenous immunoglobulin (2 g/kg), followed by slowly tapering of oral prednisolone and monthly intravenous immunoglobulin infusion (1 g/kg). There was significant reduction in seizure frequency and disappearance of epileptiform discharges from the electroencephalogram. However, the motor and cognitive improvement did not occur, and he had microcephaly and growth failure at the last follow-up. This is the 11th case report of neurodegeneration associated with NRROS gene variations, but the first report of autoimmune encephalitis being triggered by the variation in a child.

Prevalence, Diversity, and Risk Factors for Cervical HPV Infection in Women Screened for Cervical Cancer in Belém, Pará, Northern Brazil.

Background: Human papillomavirus (HPV) is the most common viral sexually transmitted infection of the reproductive tract, and cervical cancer is the most common HPV-related disease. This study estimated the prevalence, diversity of HPV genotypes, and associated risk factors in women screened for cervical cancer in northern Brazil. Methods: The cross-sectional study was conducted in Belém, Pará, in the Amazon region of Brazil, and it included 162 women who were spontaneously undergoing a Pap-smear routine. Epidemiological, sexual, and health-related information was collected by interviews, and cervical samples were collected for cytological examination and HPV-DNA detection. HPV genotypes were classified as low risk (LR) and high risk (HR) by nucleotide sequencing. Results: In total, 17.3% (28/162) of the participants had HPV-DNA, and LR-HPV was the most prevalent (71.4%). Among the 13 different types of HPV detected, HPV-11 was found most frequently (12/28; 42.9%), followed by HPV-31 (3/28; 10.7%). Of the participants with cytological alterations, HPV infection was detected in only four: two were diagnosed with low-grade squamous intraepithelial lesions (15.4%), one with atypical squamous cells of undetermined significance (7.7%), and one with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (7.7%). Of the 61 women who presented a normal cytology, 13 (21.3%) had positive tests for HPV infection, 4 (8.2%) of which were positive for a high-risk genotype. Conclusion: The prevalence of HPV was high in Belém, Pará, and especially in women who had normal cytology results, which suggests the need for greater screening for HPV infection in women’s primary health care.

Human Papillomavirüs (HPV), Servikal Smear ve Kolposkopik Biyopsi Sonuçlarının Karşılaştırılması: Serviks Kanseri Taramasında Bir Üniversite Hastanesinin 4 Yıllık Deneyimi

Aim: Cervical cancer screening guidelines gradually recommend human papillomavirus (HPV) DNA testing since sensitivity of cytology is relatively low. This study aimed to evaluate correlation between HPV, cervical smear cytology and colposcopy directed biopsy results.&#x0D; Material and Methods: Patients who underwent colposcopy directed biopsy in Ordu University Training and Teaching Hospital between January 2018 and December 2021 were retrospectively reviewed. Patients with any high-risk HPV positivity who had cervical smear cytology and colposcopy directed biopsy results were included to this study. Results of HPV subtypes, cervical smear and histologic biopsy were recorded.&#x0D; Results: A total of 734 patients were included to this study. The mean age of the patients was 41.9 ± 7.36 years. Hundred and sixty-five (22.5%) patients had HPV 16 alone, 35 (4.8%) had HPV 18 alone, 354 (48.2%) had other high-risk HPV subtypes alone and 180 (24.5%) had more than one high-risk HPV subtypes. Two hundred and ninety-eight (40.6%) had HPV 16 or HPV 18 either alone or in combination with other subtypes. Majority of the patients (55.3%) had normal cervical smear results followed by ASC-US (27%). Colposcopy directed biopsy results were as follows: 452 (61.6%) normal, 199 (27.1%) CIN 1, 36 (4.9%) CIN 2, 42 (5.7%) CIN 3 and 5 (0.7%) squamous cell cancer. 66.1% of the patients with HPV 16 and/or HPV 18 had normal cervical cytology results, but they had significantly more ≥CIN 2 lesions compared to other high-risk HPV subtypes (19.8% vs 5.5%, p

The Impact of COVID-19 on Cervical Cancer Screenings and Clinical Outcomes of Patients: A Single-Center Tertiary Healthcare Service Experience

Objective: The COVID-19 pandemic has negatively affected cancer screening activities all over the World. The accumulating data suggest that delayed admissions to screening and clinical assessments are associated with increased morbidity and mortality in cancer. This study aimed to provide data on cervical cancer screenings and clinical outcomescomparatively before and during the pandemic. Method: This study retrospectively compared the demographic and clinical characteristics, screening test results, andcolposcopy assessments of women admitted to the Obstetrics and Gynecology Department of a tertiary-care university hospital before and after March 11, 2020, considered as the date of announcement of the COVID-19 pandemic. Results: A total of 382 patients with a median age of 32 years were included (174 in pre-pandemic and 208 in pandemic periods).In HPV DNA analyses, serotypes reported as high-risk were significantly increased to 22.1%, while others had minor changes in the pandemic. In cytological studies, normal cytology results were significantly decreased to 32.8% from 45.9%, and the ASC-US diagnoses were significantly increased from 12.8% to 27.4%. In addition, the colposcopy examinations revealed that the cold knife cone was increased from zero to 15.3%, routine follow-up was decreased from 88.2% to 71.4%, normal pathologies were decreased from 40.4% to 30.1%, and CIN1 and CIN2 decreased, but CIN3 rose from 3.6% to 6.6%. The HPV DNA and colposcopy follow-up were significantly increased during the pandemic. Conclusions: This study is the first report on the increased numbers of diagnoses of advanced lesions in cervical cancer screenings during the pandemic compared to the pre-pandemic admissions in Turkey. Our results implythe need for immediate actions to normalize cervical cancer screenings to avoid any further morbidity and mortality. High-risk HPV-DNA results in the Covid period were found to be higher than before the Covid period. Keywords: Cervical cancer, screening, cervical smear, cytology, colposcopy, clinical outcomes, COVID-19, pandemic, Turkey

Human Papillomavirus (HPV) Prevalence and Type Distribution in Urban Areas of Malaysia.

Background:Cervical cancer is the third leading cause of death in Malaysia, and Human Papilloma Virus (HPV) is the principal aetiology that is responsible for its development. This study was aimed to determine the prevalence and distribution of HPV types among different age groups, ethnicity, and areas in Malaysia. Materials and Methods:A total of 764 women aged 20-74 years old within the cities of Johor Bahru, Kuala Lumpur, Ipoh, Penang, and Kota Kinabalu underwent both cervical cytological assessment and HPV DNA analysis. Cervical cytology glass slides were prepared using the liquid base technique (Path TEZT TM). HPV DNA was extracted using TANBead® Nucleic Acid Extraction Kit (Taiwan Advanced Nonotech Inc.), then the types were further identified using a DR.HPV Genotyping IVD kit. Results:The prevalence of HPV infection was 14.0% (107/764) with high-risk type at 10.7% (82/764) and low-risk type at 3.27% (25/764). The most common high-risk HPV types were HPV-52, 66, 33, 39, and 58 whereas low-risk HPV types were HPV-6, 40, and 81. The majority of HPV infections (80.37%) were detected in women with normal cytology results. The most prevalent HPV type among Chinese is 33 (n=6) followed by 16, 44, 58, 66 and 68 (n=5). Among Malays, HPV 16 and 51 were the two most prevalent types (n=2). The sensitivity of the HPV DNA test compared to cytology was 100% with a specificity of 88.37%.Conclusion:This study revealed that the most common high-risk HPV type among women living in urban areas in Malaysia is HPV 52, unfortunately which is not the type of infection the current HPV vaccine is covered for protection among females. These findings may contribute beneficial information to health care providers for the appropriate use of HPV vaccine in the prevention of cervical cancer in Malaysia.

Nationwide Rereview of Normal Cervical Cytologies before High-Grade Cervical Lesions or before Invasive Cervical Cancer

Sweden has experienced an unexpected >30% increase in cervical cancer incidence among women with normal cytological screening results. We therefore performed a nationwide assessment of false-negative cytology before invasive cervical cancer. The Swedish national cervical screening registry identified 2,150 normal cytologies taken up to 10 years before 903 cases of invasive cervical cancer. The 27 cytological laboratories in Sweden were asked to rereview the slides, and all of them completed the rereview. One thousand nine hundred fifteen slides were retrieved and reviewed. Abnormalities were found in 30% of the slides, and the proportion of slides that had a changed diagnosis on rereview increased on average by 3.9% per sampling year during 2001–2016 (p < 0.03). We also asked for rereview of normal smears taken up to 42 months before a histopathologically diagnosed high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS). 19/27 laboratories responded, and out of 6,101 normal smears taken before HSIL/AIS, 5,918 were retrieved and rereviewed. The diagnosis was changed in 25% of cases. In summary, we found an increasing time trend of false-negative smears taken before invasive cervical cancer. This indicates a decreased protection of normal cytology in the screening program supporting earlier findings that this is the main reason behind the recent Swedish increase in cervical cancer. We suggest that optimal cervical cancer control may be promoted by routine nationally coordinated rereview of negative smears before high-grade cervical lesions or invasive cervical cancer.

Risk factors of cervical cancer after a negative cytological diagnosis in Polish cervical cancer screening programme.

Risk factors of cervical cancer (CC) development are well investigated, however, those influencing the risk of a potential false negative cytology preceding diagnosis of an invasive CC are not. We have aimed to explore these factors according to the data from Organised Cervical Cancer Screening Programme (OCCSP) in Poland. A total of 2.36 million of Pap tests sampled in 2010–2012 within OCCSP were merged with the Polish National Cancer Registry to identify CC cases after abnormal cytology and after normal cytology within 3 years of screening. Of 1460 invasive CCs, 1025 were preceded by abnormal and 399 by normal cytology result. Multivariate logistic analysis indicated that the presence of microorganisms in the Pap (OR = 2.18, 95% CI 1.65–2.87), evaluation by smaller (below 9000 slides processed per year) laboratories (OR = 1.60, 95% CI 1.22–2.09) and non‐squamous histology of cancer increased the odds for a potential false negative result (OR = 3.39, 95% CI 2.37–4.85 for adenocarcinoma, OR = 1.99, 95% CI 1.11–3.55 for other types of carcinoma), whereas cervical ectropion, other macroscopic changes on the cervix and smoking decrease the odds for a potential false negative Pap test result preceding CC (OR = 0.61, 95% CI 0.45–0.82, OR = 0.41, 95% CI 0.25–0.67, OR = 0.60, 95% CI 0.46–0.78, respectively). Proper triage of women with microscopic signs of microorganisms in the Pap smear should be reconsidered and cytology should be assessed in laboratories processing over 9000 slides annually to decrease the odds for negative Pap test result in 2 years before CC diagnosis. Information on macroscopic changes on the cervix provided to cytomorphologist may reduce the risk of a potential false negative cytology result.

Analysis of 10 Pediatric Nephrotic Syndrome Cases With Complications of Cerebral Sinovenous Thrombosis.

Background: To analyze the clinical characteristics of nephrotic syndrome (NS) with complications of cerebral sinovenous thrombosis (CSVT) in children.Method: Clinical, radiographic, laboratory, and treatment data obtained from 10 confirmed cases of NS with complications of CSVT were analyzed. All patients were followed up for at least 18 months. CSVT was diagnosed by cerebral computed tomography (CT) and/or magnetic resonance imaging (MRI) with or without magnetic resonance venography (MRV) of the cerebral vessels.Results: Among 10 cases reported, 4 were steroid-sensitive NS with frequent relapse, 5 were steroid-resistant (three of them had renal biopsies showing two minimal change disease and one IgA nephropathy), and 1 was steroid-sensitive with one relapse. Common clinical manifestations were headache or ophthalmodynia complicated by vomiting, dizziness, convulsion, and coma. Neuropathologic signs were positive in some cases. Papilledema appeared in only one case with winding of vein. Cerebrospinal fluid was examined in three cases with elevated pressure but normal cytological and biochemical results. D dimer and fibrinogen levels were elevated while prothrombin time and activated partial thromboplastin time were shortened. Five out of seven cases who had performed cranial CT were suspicious for cerebral thrombosis. Nine cases had cranial MRI with abnormal signs in seven cases. All of the cases received MRV, confirming the diagnosis of CVST.Conclusion: Clinical manifestations of NS with CSVT are not specific but varied. Therefore, CSVT should be considered once nervous manifestations present. MRV is a better method in the diagnosis of CSVT.

HPV co-testing as cervical screening test, Experience of Alweiya early detection cervical clinic: one-year Analysis

Objectives: The high-risk Human papilloma virus test with conventional cytology (HPVco-test) was firstly introduced in our institute at May 2019 so we aimed to estimate the prevalence of abnormal cytology and positive high-risk human papillomavirus test results in a screening woman and to assess the accuracy between cytology and Human papilloma virus testing to evaluate the feasibility of integrating the latter as a primary test in the national cervical cancer screening program.&#x0D; Methods: A prospective study for women attending to early detection cervical clinic, during the period from May 2019 to May 2020. Patients who were sexually active were included in the study. Samples for conventional cytology and HPV by using real-time polymerase chain reaction technique for high risk types were taken concurrently. The prevalence of positive screening results and the difference in accuracy between two testing were estimated by McNemar’s χ2 test.&#x0D; Result: A total of 388 women were included in the study. The prevalence of positive test for hr-HPV was 2.1%(8) while the prevalence of abnormal cytology test was 19.1%(74), Concerning discordant pairs, 0.8%(3) of women had normal cytology with a positive hr-HPV test result and 17.8%(69) of women had abnormal cytology with a negative hr-HPV test result. A total of 311 (80.1%) women had normal cytology and negative hr-HPV test results. The proportion of women with abnormal cytology and positive hr-HPV test results was 1.3% (5 women). the difference in accuracy between the two results was statistically significant (&lt;0.0001). The prevalence of positive hr-HPV test decreased with increasing age, whereas the prevalence of abnormal cytology showed a bimodal age pattern.&#x0D; Conclusion: The prevalence of abnormal cytology was high to that of hr-HPV testing, which could not allow for the implementation of hr-HPV as a primary test in the national screening program in Iraq.

Assessment of Cervical Cancer Molecular-Based Screening Tools; HPV-DNA Detection versus E6/E7 mRNA Testing; First Report of a Prospective Cohort Study among Iranian Women.

Background:Human papillomavirus (HPV) has been found as the most considerable causes of cervical cancer. Recently, several molecular methods have been introduced to increase the accuracy of the screening programs and decrease the mortality rate. Among these methods, mRNA-based methods have more advantages as they assess the expression level of HPV E6 and E7 oncogenic mRNAs. This study aimed to evaluate the results of HPV RNA- and DNA-based methods among Iranian women population with normal cytology results.Methods:Overall, 4640 women were enrolled referred to the Gynecology Oncology Ward of Vali-e-Asr Hospital, private and academic clinics, Tehran, Iran from Jan 2016 to Apr 2018. To assess the HPV-DNA infection INNO-LiPA® HPV Genotyping Extra-II kit was used. For HPV-RNA assessment, Aptima HPV Assay and in house HPV-RNA genotyping methods were applied.Results:The positivity rates of HPV infection according to DNA- and RNA-based methods were 18.0% and 11.2%, respectively (P<0.001). The positive predictive value, negative predictive value, specificity and sensitivity of DNA-based method in contrast with RNA-based method were 59.2% (56.6–61.6), 99.4% (99.0–99.6), 91.7% (90.8–92.6) and 95.2% (93.0–96.9) respectively.Conclusion:At the present study for prognosis of cervical cancer, RNA-based method seemed to be more specific in contrast to DNA-based method. Patient follow up and further studies will be conducted in order to clarify the clinical sensitivity and specificity of the two methods.

Increase of cervical cancer incidence in Sweden in relation to screening history: population cohort study

Background: Cervical cancer incidence in Sweden decreased from 24/100,000 in 1965 to 8/100,000 in 2011, but has from 2014 increased to 11/100,000. The increase appears to correlate to screening history. We perform a study of the cancer risk change in relation to screening history over two screening rounds to verify the correlation.Material and methods: We studied the cohorts of all 3,047,850 individual women living in Sweden in each year from 2002–2015. Registry linkages between the Total Population Register, the Swedish National Cervical Screening Registry, the Swedish Cervical Cancer Audit database and the National Quality Register for Gynecological Cancer, defined the incidence rates of invasive cervical cancer comparing time periods 2002–2013 to 2014–2015, in women whose screening history in 2 screening intervals prior to each year were either (i) adequately screened with normal results (almost exclusively cytology, 52% of the population) or (ii) unscreened (13% of the population). We also investigated the incidence increase by time since a normal smear performed in 2002–2012.Results: Among women adequately screened with normal results there was a strong incidence increase in 2014–2015 compared to previous years (Incidence rate ratio (IRR) = 1.59, 95%CI = 1.36–1.85), but no significant increase among unscreened women (IRR = 1.09, 95%CI = 0.94–1.27). There was no increase in incidence 0–2.5 years after a normal smear over the study period (IRR = 1.04, 95% CI = 0.88–1.24), but a strong increase 3–4 years after a normal smear since year 2009 (IRR = 1.52, 95% CI = 1.25–1.84).Conclusion: The results suggest that the overall increase is associated with an increased cancer risk in women adequately screened with normal cytological results. Possibly, precursor lesions missed in one screening round might result in detection of early stage invasive cancer in the subsequent screening.

Recurrent disease after treatment for cervical intraepithelial neoplasia—The importance of a flawless definition of residual disease and length of follow-up

ObjectiveTo evaluate adherence to national guidelines for follow-up, and assess residual and recurrent disease after treatment for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Study designIn a case-series design women aged 25–69 years treated for primary CIN2+ in 2006–2011 (n = 752) were followed through August 9, 2019 for residual or recurrent disease, i.e., CIN2+ diagnosed before or after, respectively, two consecutive, normal post-treatment cytology results. We used the Chi-Square test to assess predictive factors of adherence to post-treatment follow-up and residual disease, and survival analyses to assess the cumulative incidence of residual and recurrent disease. ResultsStrict adherence to post-treatment follow-up was low . However, 702 (95 %) women attended at least one post-treatment follow-up visit within the suggested time window. Forty-two women (5.6%) were diagnosed with residual disease, 38 (91 %) of whom were diagnosed within 2 years of treatment. Among the 637 (85 %) women with two consecutive, normal post-treatment cytology results, cumulative incidence of recurrent disease was 1.0 (95 % confidence interval [CI]: 0.2–1.8) and 2.5 (95 % CI: 1.2–3.8) per 100 women-years within 42 and 78 months of treatment, respectively. Three women with residual and two with recurrent disease were diagnosed with cervical cancer within 78 months of treatment. Women with not-free resection margins at treatment had a significantly increased risk of residual and recurrent disease. Using a 2-year definition for residual disease would misclassify 3 of 5 cancer cases as recurrent disease when they were true cases of residual disease. ConclusionsThis study emphasizes the importance of properly distinguishing between residual and recurrent disease after treatment for CIN2 + . Many women with residual disease could benefit from an earlier colposcopy, cervical biopsy, or diagnostic conization during post-treatment follow-up in order to detect occult cervical cancer. The cumulative incidence of recurrent disease within 78 months of treatment was low.

Test Accuracy of Human Papillomavirus in Urine for Detection of Cervical Intraepithelial Neoplasia.

The objective was to assess the diagnostic test accuracy of high-risk human papillomavirus (hrHPV) testing of self-collected urine and cervicovaginal samples for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). We recruited a convenience sample of women 25 to 65 years of age who were undergoing clinically indicated colposcopy at two medical centers in North Carolina between November 2016 and January 2019. Women with normal cytology results and positive hrHPV results were also recruited. Urine samples, self-collected cervicovaginal samples, provider-collected cervical samples, and cervical biopsy samples were obtained from all enrolled women. Samples were tested for hrHPV DNA using the Onclarity assay (Becton Dickinson, Sparks, MD). Biopsy samples were histologically graded as CIN2+ or <CIN2. We calculated the sensitivity and specificity for detection of CIN2+ and assessed agreement between sample collection methods. We included 307 women (median age, 36 years) with valid histology results and triple-matched urine, self-collected cervicovaginal, and provider-collected cervical hrHPV results; 83 women (27%) had CIN2+. Urine-based hrHPV testing correctly identified 80% of CIN2+ cases (95% confidence interval [CI], 71 to 88%) using the PCR cycle threshold (CT ) established for provider-collected cervical samples, but sensitivity remained below the estimates for self-collected cervicovaginal and provider-collected cervical samples (both 94% [95% CI, 89 to 99%]). Using a higher CT cutoff value of ≤40, 90% sensitivity was achieved for urine-based hrHPV testing. Agreement between results for urine samples and self-collected cervicovaginal samples (kappa = 0.58) or provider-collected cervical samples (kappa = 0.54) was moderate. Urine-based hrHPV testing may be a promising approach to improve cervical cancer screening coverage, especially among women with limited access to health care.