Invasive Cervical Cancer Research Articles

Comparison of laparoscopically assisted lymphadenectomy with simultaneous transvaginal hysterectomy according to Schout-Amreich with abdominal radical hysterectomy for invasive cervical cancer

Целью проведенного исследования является определение возможности и эффективности хирургического лечения рака шейки матки на ранних стадиях путем лапароскопически ассистированной лимфаденэктомии с одновременной трансвагинальной гистерэктомией по Шаута-Амрейху, как альтернативы лапаротомным операциям.
 Материалы и методы. В период с 2019 по 2021 год путем лапароскопически ассистированной лимфаденэктомии с одновременной трансвагинальной гистерэктомией по Шаута-Амрейху были прооперированны 21 пациентка, в то же время расширенная радикальная абдоминальная гистерэктомия, операция Вертгейма-Мейгса проведена 22 пациенткам с раком шейки матки IA2-IB1 стадии. В двух исследуемых группах зарегистрированы клинические исходные данные, в которых не было никаких существенных различий (p>0,05).
 Результаты. Исходя из полученных результатов, статистически значимыми различиями между сравниваемым критериями, выявлено, что лапароскопически ассистированная лимфаденэктомия с одновременной трансвагинальной гистерэктомией по Шаута-Амрейху являлась меньшей по объему кровопотери (261,9 против 310,9 мл, средняя разница -49,0 мл), длительностью пребывания пациента в стационаре (7,0 против 8,0 койко-дней, средняя разница -1,0 койко-день), а также более низкие оценки боли по ВАШ (5,38 против 6,77, средняя разница 1,39). Примечательно, что в группе пациенток, которым проведена лапароскопически ассистированная лимфаденэктомия с одновременной трансвагинальной гистерэктомией по Шаута-Амрейху частота лимфореи выше, чем во второй группе исследования, а число случаев образования лимфокист выше у пациенток, которым проведена радикальная абдоминальная гистерэктомия. Данные осложнения могут отсрочить дальнейшую лучевую терапию при лечении основного заболевания.
 Вывод. Внедрение миниинвазивной хирургии в онкологическую практику расширяет способности хирургов исполнять нервосберегающие операции без издержки радикальности и снижения выживаемости у онкогинекологических больных. После перенесенных лапароскопических вмешательств уровень качества жизни пациенток значительно выше, чем у пациенток с традиционным хирургическим доступом, особенно в сфере физического и эмоционального благополучия.

PREVALENCE OF CERVICAL HUMAN PAPILLOMAVIRUS INFECTION AMONG WOMEN OF CHILDBEARING AGE IN FMC ASABA, NIGERIA

Background: Cervical Human Papillomavirus infection prevalence varies with differentenvironments. Knowledge of this will help in some cervical cancer interventions such as earlyand continuous screening. This study is aim at determining the prevalence of cervical HPVinfection among women of childbearing age attending Federal Medical Center Asaba, Nigeria.Materials and methods: A total of 99 consenting women aged between (20 -45) years wererandomly recruited and screened for HPV infection using virtual inspection by acetic acid (VIA)method. Semi-structured questionnaire was used to obtain the demographic characteristics, biodata and reproductive history of the participants. Statistical analysis was done using IBM SPSSstatistics version 21. Results: The result shows that 21(21.21%) out of 99 women thatparticipated in the study were VIA positive. 16(76.19%) out of the 21 HPV infected womenshowed cervicitis, 4(19.05%) had cervical polyps, 1 (4.16%) had invasive cervical cancer while,1(4.16%) of the participants had HPV only. Age-specific prevalence was highest among the agegroup 36 – 40 years with age groups 20 – 25 and 41-45 having the same value. Conclusions:HPV prevalence rate is high among the study population especially in women of aged between(36-40) years. Early commencement of sexual intercourse among others was associated withHPV positive. Advanced and effective method of screening is highly recommended in lowincome settings. Urgent and adequate interventions is recommended for regular HPV screeningamong women of reproductive age to reduce the spread of cervical cancer.

HPV-negative high-grade cervical precancerous lesions or invasive cancer in China: A post hoc analysis of a multicentric clinical study.

To evaluate HPV-negative cervical high-grade precancerous lesions or cancer in China. Histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were searched in a multicentric clinical study. All patients underwent cobas HPV testing, liquid-based cytology, DNA ploidy analysis, and colposcopy-guided biopsy. According to clinical practice, patients underwent p16ink4a staining and cone biopsy. Comparisons were made between HPV-negative and -positive patients for clinical characteristics. The study found 61 cases of cobas HPV-negative CIN2+ among 797 cases of histologically confirmed CIN2+, including 38 CIN2, 20 CIN3, and 3 invasive cancers. The prevalence of HPV-negative CIN2+ and CIN3+ was 7.7% (95% confidence interval [CI] 5.8-9.5) and 5.7% (95% CI 3.5-8.0), respectively. Among 24 cases with p16 staining, 20 showed p16 positivity. The proportions of normal or minor abnormalities in terms of colposcopy, cytology, and DNA ploidy were higher in HPV-negative cases than in HPV-positive cases. When adding cytology to the screening of symptomatic or previously HPV-positive women, the prevalence of HPV-negative CIN2+ or CIN3 would decrease by approximately 50%. Less than one-tenth of CIN2+ are missed by HPV-only screening, and they have smaller lesions than HPV-positive cases. Colposcopy should be considered for symptomatic or previously HPV-positive women with HPV-negative results.

The Plasma DIA-Based Quantitative Proteomics Reveals the Pathogenic Pathways and New Biomarkers in Cervical Cancer and High Grade Squamous Intraepithelial Lesion

The process of normal cervix changing into high grade squamous intraepithelial lesion (HSIL) and invasive cervical cancer is long and the mechanisms are still not completely clear. This study aimed to reveal the protein profiles related to HSIL and cervical cancer and find the diagnostic and prognostic molecular changes. Data-independent acquisition (DIA) analysis was performed to identify 20 healthy female volunteers, 20 HSIL and 20 cervical patients in a cohort to screen differentially expressed proteins (DEPs) for the HSIL and cervical cancer. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for functional annotation of DEPs; the protein-protein interaction (PPI) and weighted gene co-expression network analysis (WGCNA) were performed for detection of key molecular modules and hub proteins. They were validated using the Enzyme-Linked Immunosorbent Assay (ELISA). A total of 243 DEPs were identified in the study groups. GO and KEGG analysis showed that DEPs were mainly enriched in the complement and coagulation pathway, cholesterol metabolism pathway, the IL-17 signaling pathway as well as the viral protein interaction with cytokine and cytokine receptor pathway. Subsequently, the WGCNA analysis showed that the green module was highly correlated with the cervical cancer stage. Additionally, six interesting core DEPs were verified by ELISA, APOF and ORM1, showing nearly the same expression pattern with DIA. The area under the curve (AUC) of 0.978 was obtained by using ORM1 combined with APOF to predict CK and HSIL+CC, and in the diagnosis of HSIL and CC, the AUC can reach to 0.982. The high expression of ORM1 is related to lymph node metastasis and the clinical stage of cervical cancer patients as well as the poor prognosis. DIA-ELSIA combined analysis screened and validated two previously unexplored but potentially useful biomarkers for early diagnosis of HSIL and cervical cancer, as well as possible new pathogenic pathways and therapeutic targets.

Scientific evidence for the effectiveness of primary and secondary (screening) prevention of cervical cancer

The evidence of HPV vaccination effectiveness is overwhelming. The randomized clinical trials showed that all three vaccines currently in use, bivalent (CERVARIX), quadrivalent (GARDASIL) and nanvalent (GARDASIL9) effectively prevent HPV infection, cervical intraepithelial neoplasia (CIN) 1–3 and invasive cervical cancer. The results of clinical trials have been confirmed by real life evidence – population data from countries were vaccination of 12–13 girls started in 2006–08. HPV vaccination is safe. This is proven by long term follow up of the cohorts of vaccinated women. In 2020 the WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. The document includes the interim targets for 2030: vaccination of 90% of girls by 15 years; HPV testing based screening at age 35 and 45 of 70% of women; treatment of 90% of women with screening detected cervical pathology; treatment of 90% of women with precancerous lesions and cancer of the cervix. Under elimination of cervical cancer WHO means the decrease in its incidence down to 4 cases per 100 000 population. This goal will be achieved by 2030 in countries that started HPV vaccination 15 years ago in 2006–2007.In Russia incidence of cervical cancer is on increase since 1993 from 10, 2 to 16, 1 in 2018. It is predicted that the increase will continue and in 2030 the age standardized incidence rate will reach 20 per 100 000 women. HPV vaccination and HPV test based screening will change the direction of the trend from increase to decrease and save several hundreds of lives

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.

DNA methylation-based detection and prediction of cervical intraepithelial neoplasia grade 3 and invasive cervical cancer with the WID™-qCIN test

BackgroundCervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30. Here, we aimed to develop and validate an automatable triage test that is highly sensitive and specific independently of age and sample heterogeneity, and predicts progression to CIN3+ in HPV+ patients.ResultsThe WID™-qCIN, assessing three regions in human genes DPP6, RALYL, and GSX1, was validated in both a diagnostic (case–control) and predictive setting (nested case–control), in a total of 761 samples. Using a predefined threshold, the sensitivity of the WID™-qCIN test was 100% and 78% to detect invasive cancer and CIN3, respectively. Sensitivity to detect CIN3+ was 65% and 83% for women < and ≥ 30 years of age. The specificity was 90%. Importantly, the WID™-qCIN test identified 52% of ≥ 30-year-old women with a cytology negative (cyt−) index sample who were diagnosed with CIN3 1–4 years after sample donation.ConclusionWe identified suitable DNAme regions in an epigenome-wide discovery using HPV+ controls and CIN3+ cases and established the WID™-qCIN, a PCR-based DNAme test. The WID™-qCIN test has a high sensitivity and specificity that may outperform conventional cervical triage tests and can in an objective, cheap, and scalable fashion identify most women with and at risk of (pre-)invasive cervical cancer. However, evaluation was limited to case–control settings and future studies will assess performance and generalisability in a randomised controlled trial.

Dose-risk relationships between cigarette smoking and cervical cancer: a systematic review and meta-analysis.

Cervical cancer (CC) is the fourth most frequent cancer worldwide. Cigarette smoking has been shown to influence CC risk in conjunction with human papillomavirus (HPV) infection. The aim of this study is to provide the most accurate and updated estimate of this association and its dose-response relationship. Using an innovative approach for the identification of original publications, we conducted a systematic review and meta-analysis of studies published up to January 2021. Random effects models were used to provide pooled relative risks (RRs) of CC for smoking status. Dose-response relationships were evaluated using one-stage random effects models with linear or restricted cubic splines models. We included 109 studies providing a pooled RR of invasive CC and preinvasive lesions, respectively, of 1.70 [95% confidence interval (CI), 1.53-1.88] and 2.11 (95% CI, 1.85-2.39) for current versus never smokers, and, respectively, 1.13 (95% CI, 1.02-1.24) and 1.29 (95% CI, 1.15-1.46) for former versus never smokers. Considering HPV does not alter the positive association or its magnitude. Risks of CC sharply increased with few cigarettes (for 10 cigarettes/day, RR = 1.72; 95% CI, 1.34-2.20 for invasive CC and RR = 2.13; 95% CI, 1.86-2.44 for precancerous lesions). The risk of CC increased with pack-years and smoking duration and decreased linearly with time since quitting, reaching that of never smokers about 15 years after quitting. This comprehensive review and meta-analysis confirmed the association of smoking with CC, independently from HPV infection. Such association rose sharply with smoking intensity and decreased after smoking cessation.

8452 Lymph Node Evaluation for Endometrial Hyperplasia: A National Level Analysis of Minimally Invasive Hysterectomy in the Ambulatory Setting

<h3>Study Objective</h3> To examine the association between histology and utilization of lymph node evaluation at the time of minimally invasive hysterectomy when performed for endometrial hyperplasia in an ambulatory surgery setting. <h3>Design</h3> Population-based, retrospective cohort study. <h3>Setting</h3> The National Ambulatory Surgery Sample, 2016-2019. <h3>Patients or Participants</h3> 39,205 patients with endometrial hyperplasia who underwent minimally invasive hysterectomy (total laparoscopic, laparoscopic assisted vaginal, and total vaginal), including 19,653 cases with atypia and 19,552 cases without atypia. Patients with invasive uterine, cervical, and ovarian cancers were excluded. <h3>Interventions</h3> <i>(i)</i> Multivariable analysis with log-Poisson generalized linear regression model to compare the clinical characteristics between the atypia and non-atypia groups, and <i>(ii)</i> inverse probability of treatment weighting to assess the utilization of lymph node evaluation at the time of hysterectomy, stratified by histology type. <h3>Measurements and Main Results</h3> In a multivariable analysis, patients in the atypia group were more likely to have older ages, obesity, medical comorbidities, a recent diagnosis, self-paid insurance, higher household incomes, and undergo surgery at large, urban teaching centers compared to those in the non-atypia group (all, <i>P</i><0.05). Patients in the atypia group were less likely to undergo laparoscopic assisted vaginal or total vaginal hysterectomy compared to those in the non-atypia group (both, <i>P</i><0.05). In a propensity score-weighted model, patients in the atypia group were more likely to have lymph node evaluation at the time of hysterectomy compared to those in the non-atypia group (8.8% <i>versus</i> 2.8%, odds ratio 3.37, 95% confidence interval 3.02-3.77). <h3>Conclusion</h3> This national-level analysis suggests that lymph node evaluation was performed at the time of minimally invasive hysterectomy for endometrial hyperplasia in the ambulatory surgery setting in the United States from 2016-2019. Surgeons appear to evaluate lymph nodes more frequently for endometrial hyperplasia with atypia than without.

HPV genotyping in biopsies of HSIL and invasive cervical cancers in women living with HIV: A cohort- and a nested -case control study

ObjectiveTo characterize HPV genotype distribution in HSIL and ICC- biopsies, of WLWH, in Europe, as compared to HIV-negative women. DesignCohort- and nested -case control study. MethodWe characterized HPV genotype distribution by performing PCR on HSIL and ICC biopsies from WLWH (n = 170); 85 cases were compared to 85 HIV-negative matched controls. The proportion of patients that might be protected by HPV vaccines was estimated. ResultsAmong WLWH (median age 36 years-old, median duration of HIV infection 70,5 months, 79% under cART): the most frequently detected HPV were HPV16 (30%), HPV35 (16%), HPV58 (14,7%), HPV31 (13,5%), and HPV52 (11,7%). HPV16 was less frequently found in WLWH, originating from Central Africa (20,5%) compared to other African regions (35,5%) (p = 0,05) or world regions (38,8%) (p = 0,007). Multiple versus single high-risk HPV infections were associated with younger age (≤35 years)(odds ratio (OR) 2,65 (95%IC: 1,3–5,2,p = 0,002), lymphocyte CD4 count < 350 cells / µL (OR 2,7 (95%IC: 2–8,5; p = 0,005), use of cART for < 18 month OR 2,2 (95%IC: 1,1–4,5),p = 0,04) or a cumulative time with undetectable HIV viral load of less than 12 months (OR 4,2 (95%IC: 2–8.5,p = 0,001). HPV 31, 33 and 35 were more frequently detected in samples from WLWH than in HIV-negative controls (p < 0,05). The 9-valent vaccine would increase HPV protection, in HIV-positive and negative women (p < 0,001). ConclusionWLWH are more frequently infected with high-risk HPV other than 16 and 18 than HIV-negative ones. The use of 9-valent vaccine may prevent HSIL or ICC in up to 85% of the women. Adding HPV 35 to the HPV vaccine panel, might improve vaccine effectiveness in WLWH.

Effect of Human Immunodeficiency Virus Infection on Human Papillomavirus Clearance Among Women in Senegal, West Africa.

Persistent infection with high-risk human papillomavirus (HPV) is associated with development of invasive cervical cancer. Longitudinal data was collected from 174 Senegalese women. We employed marginal Cox proportional hazards models to examine the effect of human immunodeficiency virus (HIV) status (HIV positive vs HIV negative) and HIV type (HIV-1 vs HIV-2 vs dual HIV-1/HIV-2) on clearance of type-specific HPV infection. Analyses were stratified by incident versus prevalent HPV infection. Incident HPV infections in HIV-positive women were less likely to clear than those in HIV-negative women (adjusted hazard ratio [HR] = 0.60; 95% confidence interval [CI], .38-.94). Among HIV-positive women, HIV-2-infected women and HIV-1/2 dually infected women were more likely to clear HPV incident infections than HIV-1-infected women (HR = 1.66; 95% CI, .95-2.92 and HR = 2.17; 95% CI, 1.12-4.22, respectively). Incident HPV infections in HIV-positive women with CD4 cell count ≤500 cells/μL were less likely to clear than those in HIV-positive women with CD4 cell count >500 cells/μL (HR = 0.65; 95% CI, .42-1.01). No significant associations were observed for prevalent HPV infections. HIV infection reduced the likelihood of clearance of incident HPV infection. Furthermore, among HIV-positive women, low CD4 cell count and dual HIV infection were each associated with reduced likelihood of clearance.

Stage and outcomes of invasive cervical cancer patients in Botswana: A prospective cohort study from 2013 to 2020

ObjectiveTo present the stage distribution, patterns of care, and outcomes of patients from Botswana with invasive cervical cancer, living with or without HIV. MethodsBetween 2013 and 2020, women with cervical cancer were prospectively enrolled in an observational cohort study. ResultsA total of 1,043 patients were enrolled; 69% were women living with HIV. The median age of the cohort was 47 years (interquartile range [IQR] 40–58 years), with women living with HIV presenting at a younger age compared to women without HIV (44 versus 61 years, p < 0.001). Among women living with HIV, the median CD4 count at the time of cancer diagnosis was 429.5 cells/μL (IQR 240–619.5 cells/μL), 13% had a detectable viral load, and 95% were on antiretroviral therapy. In regard to treatment, 6% (n = 58) underwent surgery, 33% (n = 341) received radiation therapy, 51% (n = 531) received chemoradiation, and 7% (n = 76) did not receive treatment. Stage distribution in the cohort was as follows: I 17% (n = 173), II 37% (n = 388), III 35% (n = 368), and IV 8% (n = 88). For all patients, 2-year OS was 67%. In multivariable Cox regression, worse OS was associated with stage: II (HR 1.91, p = 0.007), III (HR 3.99, p < 0.001), and IV (HR 5.06, p < 0.001) compared to stage I. Improved OS was associated with hemoglobin > 10 g/dL (HR 0.51, p < 0.001) compared to Hb ≤ 10 g/dL. ConclusionsAmong women in Botswana with cervical cancer, most patients presented with stage II or III disease warranting radiation therapy or chemoradiation. While two-thirds of cervical cancer patients were women living with HIV, HIV did not impact OS.

Effectiveness of Cervical Testing in and outside a Screening Program-A Case-Control Study.

In many countries with organized cervical cancer screening, opportunistic Pap and human papillomavirus (HPV) tests are common. However, little is known about their effectiveness. We examined the effect of testing in and outside the Finnish screening program on the risk of cervical cancer. We conducted a case-control study that involved 1677 cases with invasive cervical cancer that were diagnosed between 2010 and 2019. Five- and three-year test intervals were analyzed across all ages, by age group and by cancer morphology subtype. Conditional logistic regression was used, adjusting for socioeconomic variables. Women undergoing any kind of cervical test had a significantly lowered risk of cervical cancer (adjusted OR = 0.43, 95% CI = 0.38-0.48, tests in five-year intervals). The results were similar, regardless of whether the test had been taken in the screening program or outside of it, or whether the interval was five years or three years. Testing of women at ages 35-64 showed the strongest effects, but moderate preventive effects were seen until age 79. No significant effect was seen below age 30. Tests in and outside the program were effective at the screening target age. However, participation in the program should be encouraged for optimal cost-effectiveness. Preventive effects were also seen above the program target ages.

The WID-CIN test identifies women with, and at risk of, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer

BackgroundCervical screening is transitioning from primary cytology to primary human papillomavirus (HPV) testing. HPV testing is highly sensitive but there is currently no high-specificity triage method for colposcopy referral to detect cervical intraepithelial neoplasia grade 3 or above (CIN3+) in women positive for high-risk (hr) HPV subtypes. An objective, automatable test that could accurately perform triage, independently of sample heterogeneity and age, is urgently required.MethodsWe analyzed DNA methylation at ~850,000 CpG sites across the genome in a total of 1254 cervical liquid-based cytology (LBC) samples from cases of screen-detected histologically verified CIN1-3+ (98% hrHPV-positive) and population-based control women free from any cervical disease (100% hrHPV-positive). Samples were provided by a state-of-the-art population-based cohort biobank and consisted of (i) a discovery set of 170 CIN3+ cases and 202 hrHPV-positive/cytology-negative controls; (ii) a diagnostic validation set of 87 CIN3+, 90 CIN2, 166 CIN1, and 111 hrHPV-positive/cytology-negative controls; and (iii) a predictive validation set of 428 cytology-negative samples (418 hrHPV-positive) of which 210 were diagnosed with CIN3+ in the upcoming 1–4 years and 218 remained disease-free.ResultsWe developed the WID-CIN (Women’s cancer risk IDentification-Cervical Intraepithelial Neoplasia) test, a DNA methylation signature consisting of 5000 CpG sites. The receiver operating characteristic area under the curve (AUC) in the independent diagnostic validation set was 0.92 (95% CI 0.88–0.96). At 75% specificity (≤CIN1), the overall sensitivity to detect CIN3+ is 89.7% (83.3–96.1) in all and 92.7% (85.9–99.6) and 65.6% (49.2–82.1) in women aged ≥30 and <30. In hrHPV-positive/cytology-negative samples in the predictive validation set, the WID-CIN detected 54.8% (48.0–61.5) cases developing 1–4 years after sample donation in all ages or 56.9% (47.6–66.2) and 53.5% (43.7–63.2) in ≥30 and <30-year-old women, at a specificity of 75%.ConclusionsThe WID-CIN test identifies the vast majority of hrHPV-positive women with current CIN3+ lesions. In the absence of cytologic abnormalities, a positive WID-CIN test result is likely to indicate a significantly increased risk of developing CIN3+ in the near future.

HPV genotype prevalence in Indian women with cervical disease and estimation of the potential impact of HPV vaccines on prevention of cervical cancer

PurposeHuman papillomavirus (HPV) causes genital and oropharyngeal cancers worldwide. There are significant gaps exist in the data on HPV genotype prevalence in this part of the country. HPV vaccination is one of the best preventive methods available currently. HPV genotyping plays an important role in the selection of appropriate vaccines and monitoring vaccine efficacy and coverage. The present study aimed to determine the HPV genotype prevalence and to estimate the potential impact of HPV vaccines on invasive cervical cancer. Materials and methodsA total of 204 cervical biopsy samples collected from symptomatic women were subjected to an in-house designed and standardised nested multiplex PCR (NM-PCR) assay. The NM-PCR was designed to detect 38 Mucosal HPV types as a pooled result and genotyping of 15 HPV types. Further, the HPV genotype data was used to estimate the HPV vaccine bivalent, quadrivalent and nonavalent impact on the population using a mathematical formula. ResultsOut of 204 samples 188 were subjected to HPV-nested PCR. A total of 163 (86.7%) samples were positive for at least one HPV type. Multiple genotypes were identified in 30% of samples processed. HPV-16 (85.3%) was the most frequently detected genotype followed by HPV-18 (13.5%) and HPV-33 (11.0%). Other genotypes were observed less frequently. Based on the HPV prevalence observed in the study a mathematical model estimated the efficacy of bivalent, quadrivalent and nonavalent vaccines were 76.1%, 76.7%, and 91.1% (average) respectively. ConclusionsHPV-16 was the most prevalent (>85%) genotype detected in this study. Multiple infections observed in 30% of samples were quite high as compared to the majority of national, and global reference (15–25.4%) data. The Mathematical model showed that a nonavalent vaccine would give better protection.

Whole-genome analysis of human papillomavirus 67 isolated from Japanese women with cervical lesions

BackgroundHuman papillomavirus (HPV) type 67 is phylogenetically classified into Alphapapillomavirus species 9 (alpha-9) together with other carcinogenic types (HPV16, 31, 33, 35, 52 and 58), but is the only alpha-9 type defined as possibly carcinogenic. This study aimed to determine whole-genome sequences of HPV67 isolated from Japanese women with cervical cancer or cervical intraepithelial neoplasia (CIN) to better understand the genetic basis of the oncogenic potential of HPV67.MethodsTotal cellular DNA isolated from cervical exfoliated cells that were single positive for HPV67 (invasive cervical cancer, n = 2; CIN3, n = 6; CIN 2, n = 1; CIN1, n = 2; the normal cervix, n = 1) was subjected to PCR to amplify HPV67 DNA, followed by next generation sequencing to determine the complete viral genome sequences. Variant lineages/sublineages were assigned through viral whole-genome phylogenetic analysis. The transcriptional activity of the virus early promoter was assessed by luciferase reporter assays in cervical cancer cell lines.ResultsPhylogenetic analyses of HPV67 genomes from Japan (n = 12) revealed that 11 belonged to lineage A (sublineage A1, n = 9; sublineage A2, n = 2) and one belonged to lineage B. All cancer cases contained sublineage A1 variants, and one of these contained an in-frame deletion in the E2 gene. The long control region of the HPV67 genome did not induce transcription from the virus early promoter in HeLa cells, but showed weak transcriptional activity in CaSki cells.ConclusionsThe single detection of HPV67 in cervical cancer and precancer specimens strongly suggests the carcinogenic potential of this rare genotype. The phylogenetic analysis indicates a predominance of lineage A variants among HPV67 infections in Japan. Since only 23 complete genome sequences of HPV67 had been obtained until now, the newly determined genome sequences in this study are expected to contribute to further functional and evolutionary studies on the genetic diversity of HPV67.

PAX1 Methylation Status in Cervical Scrapes as Novel Diagnostic Biomarker in CIN 2/3 and Invasive Squamous Cell Carcinoma.

DNA methylation of paired box-1 (PAX-1) gene has been shown to be a potential biomarker for the detection of high-grade cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer. The objective of this pilot study was to quantify and compare methylation percentage of PAX1 gene in benign cervical lesion, pre-invasive and invasive cervical cancer. A total of 200 screen positive women (VIA, VILI and Pap test) underwent colposcopy. Cervical scrapes taken were taken and stored for DNA analysis and PAX 1 methylation status. Women with Swede score of 5 or more (n = 98) were biopsied. Cervical scrapes and biopsy were taken from women with obvious cervical growth (n = 14), without prior colposcopy. Sixty women were recruited to the study and allocated into three groups on the basis of histopathology, i.e., benign cervix (Group 1; n = 20), CIN 2/3 (Group 2; n = 20) and invasive cervical carcinoma (Group; n = 20). PAX 1 methylation percentage was calculated from the DNA extracted from the cervical scrapes of the women recruited. The mean PAX1 methylation percentage in benign lesions, CIN 2/3 and invasive cancer was 9.58% (SD ± 2.37%), 18.21% (SD ± 2.67%) and 24.34% (SD ± 4.09%), respectively, with p-value of < 0.001. PAX 1 gene methylation has a promising role in identifying high-grade lesions and invasive cancer.

Reason for improper simple hysterectomy in invasive cervical cancer in Northeast India.

The objective of the study was to determine the reasons for improper simple hysterectomy in the presence of invasive cervical cancer in Northeast India. The medical records of 52 patients who had undergone improper simple hysterectomy in the presence of invasive cervical cancer and were referred to a tertiary regional cancer Institute at Guwahati, Assam, between January 2015 and December 2019 were reviewed. Most of the patients presented with abnormal vaginal bleeding (40.4%). The failure to perform cervical cytology before the operation was quite high at 48.1% (25 patients). Interestingly, normal cytologic smear could still be found in 15.4% (8 patients) despite the presence of invasive cervical cancer. Failure to perform preoperative Papanicolaou smear, incomplete evaluation of cervical intraepithelial neoplasia (CIN) on cervical biopsy, and negative Papanicolaou smear accounted for 75% of the patients undergoing inappropriate simple hysterectomy. The most common indications for inappropriate operation were abnormal vaginal bleeding (40.4%) and CIN (19.2%). The reasons for inappropriate simple hysterectomy included lack of preoperative cervical cytology (48.1%), false-negative cervical cytology (15.4%), incomplete evaluation of cervical dysplasia or microinvasion on biopsy (11.5%). failure to perform indicated conization( 5.8%), emergency hysterectomy (3.8%), errors in colposcopic examination (3.8%), incomplete evaluation of an abnormal cervical cytology (3.8%), failure to review slide (3.8%) and failure to biopsy a gross cervica lesion (3.8%). Most improper simple hysterectomy resulted from deviation from guideline for cervical cancer detection protocols. Improper simple hysterectomy in the presence of invasive cervical cancer can be avoided if one sticks to the diagnostic guideline for patients with an abnormal cervical cytology.

S3519 A Rare Case of Epigastric Pain Caused by Duodenal Metastatic Cervical Cancer

Introduction: Cervical cancer was previously one of the most common causes of death for women in the United States but survival has since improved with the use of screening and the HPV vaccine. Metastatic cervical cancer spread to the duodenum is rare and presents a diagnostic challenge due to vague symptoms. We present a case of epigastric pain caused by invasive squamous cell cervical cancer with duodenal metastasis. Case Description/Methods: A 59-year-old female with a history of GERD and treated cervical cancer (2 years prior) and currently on pembrolizumab presented to clinic for 3 months of progressive upper abdominal pain and dyspepsia. Last upper endoscopy a year ago was normal. Physical exam was notable for epigastric tenderness without guarding. Laboratory data was remarkable for downtrending hemoglobin, normal liver function tests, normal lipase, and negative stool H pylori antigen. She was referred for EGD. A contrasted CT of the abdomen and pelvis performed revealed multiple enlarged lymph nodes of the mesentery. Upper endoscopy revealed thickened folds of the second portion of the duodenum and multiple biopsies taken of this site. It was an otherwise normal upper endoscopy. The duodenal biopsies were positive for metastatic squamous cancer of the cervix. The patient was transitioned to treatment with gemcitabine and carboplatin due to progressive disease on pembrolizumab. She unfortunately succumbed to her disease six months later. (Figure) Discussion: There is an estimated 7.5 per 100,000 new cases of cervical cancer per year with death rate of 2.2 per 100,000 in the United States. Cervical cancer is usually locally invasive and spreads by lymphatics or hematogenously with most common metastatic sites of lungs, liver, and bone. In a previous review, liver metastases was in up to 12.5% of patients but did not mention a single case of luminal disease. It is very rare for most cancers to metastasize to the gastrointestinal tract, but when present, metastasis has a predilection for the stomach and duodenum. Few case reports are available for cervical cancer metastasis to the GI tract specifically, with about 16 identified. These patients generally presented with gastrointestinal bleeding, bowel perforation, nonspecific abdominal pain or obstructive symptoms. In conclusion, duodenal metastasis of cervical cancer is rare and can be frequently missed. A high degree of suspicion can expedite referral for upper endoscopy to diagnose and allow for treatment to extend patients’ quality of life.Figure 1.: Thickened folds in the second portion of duodenum.

Assessment of reproductive outcomes and quality of life in patients after radical trachelectomy

Cervical cancer occupies a leading position in the structure of oncogynecological pathology. Radical trachelectomy (RT) has entered the standards of treatment of invasive cervical cancer in patients of reproductive age. RT can be performed by transabdominal and laparoscopic approaches. The purpose of our study was a comparative assessment of the effectiveness and study of the quality of life in patients after RT. In total, 99 surgical interventions were performed using technologies developed at Oncology Research Institute, Tomsk National Research Medical Center of Russian Academy of Sciences. The features and results of treatment are described, including oncological efficacy, reproductive results (reproductive potential, peculiarities of the course of pregnancies and childbirth). The analysis of the study of the quality of life of patients after RT according to the criteria of modern questionnaires EORTC QlQC30 and QLQ-CX24.