Genotype, cervical intraepithelial neoplasia, and type-specific cervical intraepithelial neoplasia distributions in hrHPV+ cases referred to colposcopy: A multicenter study of Chinese mainland women.

To investigate age and type-specific prevalences of high-risk human papillomavirus (hrHPV) and cervical intraepithelial neoplasia (CIN) in hrHPV+ women referred to colposcopy. This is a retrospective, multicenter study. Participants were women referred to one of seven colposcopy clinics in China after testing positive for hrHPV. Patient characteristics, hrHPV genotyping, colposcopic impressions, and histological diagnoses were abstracted from electronic records. Main outcomes were age-related type-specific prevalences associated with hrHPV and CIN, and colposcopic accuracy. Among 4419 hrHPV+ women referred to colposcopy, HPV 16, 52, and 58 were the most common genotypes. HPV 16 prevalence was 39.96%, decreasing from 42.57% in the youngest group to 30.81% in the eldest group. CIN3+ prevalence was 15.00% and increased with age. As lesion severity increases, HPV16 prevalence increased while the prevalence of HPV 52 and 58 decreased. No age-based trend was identified with HPV16 prevalence among CIN2+, and HPV16-related CIN2+ was less common in women aged 60 and above (44.26%) compared to those younger than 60 years (59.61%). Colposcopy was 0.73 sensitive at detecting CIN2+ (95% confidence interval[CI]: 0.71, 0.75), with higher sensitivity (0.77) observed in HPV16+ women (95% CI: 0.74, 0.80) compared to HPV16- women (0.68, 95% CI: 0.64, 0.71). Distributions of hrHPV genotypes, CIN, and type-specific CIN in Chinese mainland hrHPV+ women referred to colposcopy were investigated for the first time. Distributions were found to be age-dependent and colposcopic performance appears related to HPV genotypes. These findings could be used to improve the management of women referred to colposcopy.

Galectin-9 Expression is Correlated to Cervical Squamous Cell Carcinoma Progression and Overall Survival.

Purpose: To determine whether galectin-9 gene (LGALS9) expression is correlated with cervical cancer progression, clinicopathological characteristics, and overall survival. To determine the biological processes and the abundance of tumour infiltrating immune cells related to the expression of LGALS9. Patients and Methods: The study was conducted in two phases: 1) The expression level of LGALS9 was determined using the data of 193 squamous cell carcinoma (SCC) samples from The Cancer Genome Atlas (TCGA) database. Biological processes and tumour infiltrating cells associated to LGALS9 expression were evaluated using gene set enrichment analysis (GSEA) and tumour immune estimation resource (TIMER). 2) Independently, galectin-9 was identified in 40 SCC samples by immunohistochemistry and optical density quantified using ImagePro® software. Results: The LGALS9 gene showed increased expression in cervical cancer samples. A higher expression level in SCC was related to better overall survival and to early clinical stages. GSEA showed that tumours with higher expression of LGALS9 were enriched in immune pathways such as interferon_alpha_response, and complement, the analysis of TIMER database showed a positive correlation between the expression level of LGALS9 and the abundance of tumour infiltrating immune cells. In addition, higher expression of galectin-9 was found in biopsies of SCC patients at early clinical stages, showing a trend of better survival. Conclusion: Higher expression levels of LGALS9 and galectin-9 in SCC were related to early clinical stages and better prognosis. GSEA and TIMER analysis suggested that galectin-9 could play an antitumor role in cervical SCC.

Prevalence and factors associated with cervical cancer preventive screening in a Peruvian region. / Prevalencia y factores asociados al tamizaje preventivo del cáncer cervical en una región de Perú.

Introduction: Preventive screening for cervical cancer is the best available strategy to reduce the incidence and mortality from this neoplasm. However, the low proportion of women who undergo routine screening is a pending concern for healthcare systems worldwide. Objective: To estimate the prevalence and factors associated with preventive cervical cancer screening in a Peruvian region. Methods: Cross-sectional, multicenter study. It enrolled 1146 women users of healthcare centers in a Peruvian sanitary region. The dependent variable was the performance of cervical cancer preventive screening with Papanicolaou or visual inspection with acetic acid in the last two years. The independent variables were sociodemographic and socio-sanitary factors, knowledge about cervical cancer and human papillomavirus, attitudes and information towards screening tests. To evaluate the association between the variables, crude and adjusted prevalence ratios were calculated with generalized linear models of Poisson. Results: The overall prevalence of preventive screening was 50.5%. This was associated with being tested, having a higher education level and urban area of residence, using contraceptive methods, having health insurance, being recommended by healthcare personnel to be screened, and being concerned about developing cervical cancer. It was also associated with responding that this cancer is preventable, being aware of cervical cancer or human papillomavirus, and believing it can cause cervical cancer. In contrast, considering preventive screening risky was associated with not having the test. Conclusions: The proportion of women with preventive cervical cancer screening is low. In addition, certain associated modifiable factors were identified, which could improve preventive screening behaviors and rates.

Introducción: El tamizaje preventivo del cáncer cervical es la mejor estrategia disponible para mermar la incidencia y mortalidad por esta neoplasia. No obstante, la baja proporción de mujeres que se someten al tamizaje de rutina, constituye un problema pendiente para los sistemas de salud del mundo. Objetivo: Estimar la prevalencia y los factores asociados a realizarse el tamizaje preventivo del cáncer cervical en una región de Perú. Métodos: Estudio transversal y multicéntrico. En él participaron 1146 mujeres usuarias de centros de salud de una región sanitaria de Perú. La variable dependiente fue la realización de un tamizaje preventivo de cáncer cervical con Papanicolaou o inspección visual con ácido acético, en los últimos dos años. Las variables independientes fueron factores sociodemográficos, sociosanitarios, conocimientos sobre cáncer de cuello uterino y virus del papiloma humano, actitudes e información ante las pruebas de tamizaje. Para evaluar la asociación entre las variables se calcularon razones de prevalencia crudas y ajustadas, con modelos lineales generalizados de la familia Poisson. Resultados: La prevalencia general del tamizaje preventivo fue de 50,5%. Esta se asoció a realizarse la prueba, el grado de instrucción superior y área de residencia urbana, usar métodos anticonceptivos, tener seguro de salud, recibir recomendación del personal de salud para realizarse el tamizaje y sentirse preocupada por adquirir cáncer de cuello uterino. También se vinculó a quienes respondieron que el cáncer es prevenible, que habían oído hablar de cáncer cervicouterino o virus del papiloma humano y si cree que este virus puede causar cáncer de cuello uterino, Además, se asoció el admitir que existe posibilidad de curar el cáncer con su detección temprana. En cambio, el considerar riesgoso el tamizaje preventivo se relacionó con no realizarse la prueba. Conclusiones: La proporción de mujeres con tamizaje preventivo de cáncer cervical es baja. Asimismo, se identificaron ciertos factores asociados modificables, los que podrían mejorar las conductas y tasas del tamizaje preventivo.

Prevalencia y factores asociados al tamizaje preventivo del cáncer cervical en una región de Perú / Prevalence and factors associated with cervical cancer preventive screening in a Peruvian region

Introducción El tamizaje preventivo del cáncer cervical es la mejor estrategia disponible para mermar la incidencia y mortalidad por esta neoplasia. No obstante, la baja proporción de mujeres que se someten al tamizaje de rutina, constituye un problema pendiente para los sistemas de salud del mundo Objetivo Estimar la prevalencia y los factores asociados a realizarse el tamizaje preventivo del cáncer cervical en una región de Perú Métodos Estudio transversal y multicéntrico. En él participaron 1146 mujeres usuarias de centros de salud de una región sanitaria de Perú. La variable dependiente fue la realización de un tamizaje preventivo de cáncer cervical con Papanicolaou o inspección visual con ácido acético, en los últimos dos años. Las variables independientes fueron factores sociodemográficos, sociosanitarios, conocimientos sobre cáncer de cuello uterino y virus del papiloma humano, actitudes e información ante las pruebas de tamizaje. Para evaluar la asociación entre las variables se calcularon razones de prevalencia crudas y ajustadas, con modelos lineales generalizados de la familia Poisson. Resultados La prevalencia general del tamizaje preventivo fue de 50,5%. Esta se asoció a realizarse la prueba, el grado de instrucción superior y área de residencia urbana, usar métodos anticonceptivos, tener seguro de salud, recibir recomendación del personal de salud para realizarse el tamizaje y sentirse preocupada por adquirir cáncer de cuello uterino. También se vinculó a quienes respondieron que el cáncer es prevenible, que habían oído hablar de cáncer cervicouterino o virus del papiloma humano y si cree que este virus puede causar cáncer de cuello uterino, Además, se asoció el admitir que existe posibilidad de curar el cáncer con su detección temprana. En cambio, el considerar riesgoso el tamizaje preventivo se relacionó con no realizarse la prueba. Conclusiones La proporción de mujeres con tamizaje preventivo de cáncer cervical es baja. Asimismo, se identificaron ciertos factores asociados modificables, los que podrían mejorar las conductas y tasas del tamizaje preventivo

Introduction Preventive screening for cervical cancer is the best available strategy to reduce the incidence and mortality from this neoplasm. However, the low proportion of women who undergo routine screening is a pending concern for healthcare systems worldwide. Objective To estimate the prevalence and factors associated with preventive cervical cancer screening in a Peruvian region. Methods Cross-sectional, multicenter study. It enrolled 1146 women users of healthcare centers in a Peruvian sanitary region. The dependent variable was the performance of cervical cancer preventive screening with Papanicolaou or visual inspection with acetic acid in the last two years. The independent variables were sociodemographic and socio-sanitary factors, knowledge about cervical cancer and human papillomavirus, attitudes and information towards screening tests. To evaluate the association between the variables, crude and adjusted prevalence ratios were calculated with generalized linear models of Poisson. Results The overall prevalence of preventive screening was 50.5%. This was associated with being tested, having a higher education level and urban area of residence, using contraceptive methods, having health insurance, being recommended by healthcare personnel to be screened, and being concerned about developing cervical cancer. It was also associated with responding that this cancer is preventable, being aware of cervical cancer or human papillomavirus, and believing it can cause cervical cancer. In contrast, considering preventive screening risky was associated with not having the test. Conclusions The proportion of women with preventive cervical cancer screening is low. In addition, certain associated modifiable factors were identified, which could improve preventive screening behaviors and rates.

Neoplasia cervical e infección por virus del papiloma humano como factores de riesgo para desarrollo de cáncer anal y lesiones precursoras / Cervical neoplasia and human papilloma virus infection as risk factors for the development of anal cancer and precursor lesions

RESUMEN La incidencia del cáncer anal ha presentado un incremento en los últimos 10 años, sobre todo en población considerada vulnerable. Las mujeres con antecedentes de infección por Virus del Papiloma Humano (VPH) en el tracto genital, tienen mayor riesgo de este tipo de cáncer. Se ha demostrado que, la infección con genotipos de VPH de alto riesgo (AR), en la región anogenital, desempeña un papel en la etiopatogenia de dicho cáncer. Se desconocen muchos aspectos de la historia natural de las lesiones anales, pero se considera que la zona de transición anal presenta un alto recambio celular, por lo que se ha planteado un mecanismo fisiopatológico de infección por VPH-AR y desarrollo de lesiones invasoras, similar al del cáncer cervical. El objetivo de este trabajo fue mostrar el estado actual sobre la información epidemiológica que vincula el riesgo de desarrollar cáncer anal en mujeres con lesiones precursoras de cáncer cervical asociadas a la infección por VPH. La relevancia de dicha información es proporcionar una base de recomendaciones para la detección oportuna de cáncer anal en mujeres consideradas de AR de padecerlo y, favorecer la realización de estudios prospectivos en la población.

ABSTRACT The incidence of anal cancer has increased in the last 10 years, especially in the population considered to be at risk. Women with a history of infection in the genital tract by Human Papillomavirus (HPV) have higher risk of developing this type of cancer. The presence of high-risk (HR) HPV genotypes in the anogenital region has been shown to play a role in the etiopathogenesis of anal cancer. Many aspects of the natural history of anal lesions are unknown, but the anal transition zone is considered to have a high cell replacement. This is why a pathophysiological mechanism of HR-HPV infection and development of invasive lesions similar to those of cervical cancer has been suggested. The aim of this work was to show the current status of the epidemiological information that links the risk of developing anal cancer in women with cervical cancer precursor lesions associated with HPV infection. The relevance of this information is to provide a basis of recommendations for the timely detection of anal cancer in women considered to be at HR of suffering it, and to encourage more prospective studies in this population.

Contribution of HLA-G and FOXP3 genes and proteins in the severity of cervical intraepithelial neoplasia during HPV infection.

Human Papillomavirus (HPV) persistence leads to the chronification of cervical inflammation, where HLA-G and Foxp3; immunomodulatory molecules, may contribute to the aggravation of the lesion and cancerization. Here, we evaluated the synergic effect of these two molecules in the worsening of the lesion in presence of HPV infection. Hundred and eighty (180) women cervical cells and biopsies were collected for (i) HLAG Sanger sequencing and gene expression, and (ii) HLA-G and Foxp3 molecule expressions by immunohistochemistry. 53 women were HPV+ against 127 women HPV-. HPV+ women were more at risk of having cytological changes (p ≤ 0.0123), histological changes (p < 0.0011), and cervical lesion (p = 0.0004). The HLA-G + 3142CC genotype predisposed women to infection (p = 0.0190), while HLA-G + 3142C and +3035 T alleles were associated with HLA-G5 transcript expression. Both sHLA-G (p = 0.030) and Foxp3 (p = 0.0002) proteins were higher in cervical lesion as well as in high-grade lesion. In addition, sHLA-G+ cells were positively correlated to Foxp3+ cells in presence of HPV infection and in cervical grade II/III injuries. In conclusion, HPV may use HLA-G and Foxp3 as a way of host immune escape contributing to the persistence of infection and inflammation, leading to the cervical lesion and the worsening of lesions.

Cost analysis of three-dimensional radiation therapy versus intensity-modulated chemoradiotherapy for locally advanced cervical cancer in Peruvian citizens.

Background and objectives: The standard treatment for locally advanced cervical cancer (CC) is chemoradiotherapy (CTRT) followed by high-dose-rate brachytherapy (HDRBT). The ideal scenario would be under novel intensity-modulated radiation therapy (IMRT) volumetric-modulated arc therapy (VMAT) radiation techniques over three-dimensional (3D) radiation therapy. However, radiotherapy (RT) centres in low- and middle-income countries have limited equipment for teletherapy services like HDRBT. This is why the 3D modality is still in use. The objective of this study was to analyse costs in a comparison of 3D versus IMRT versus VMAT based on clinical staging. Materials and methods: From 02/01/2022 to 05/01/2023 a prospective registry of the costs for oncological management was carried out for patients with locally advanced CC who received CTRT ± HDRBT. This included the administration of radiation with chemotherapy. The cost associated with patient and family transfers and hours in the hospital was also identified. These expenses were used to project the direct and indirect costs of 3D versus IMRT versus VMAT. Results: The treatment regimens for stage IIIC2, including 3D and novel techniques, are those with the highest costs. The administration of 3D RT for IIIC2 and novel IMRT or VMAT techniques, is $3,881.69, $3,374.76, and $2,862.80, respectively. The indirect cost from stage IIB to IIIC1 in descending order is IMRT, 3D and VMAT, but in IIIC2 the novel technique regimens reduce by up to 33.99% compared to 3D. Conclusion: In RT centres with an available supply of RT equipment, VMAT should be preferred over IMRT/3D since it reduces costs and toxicity. However, in RT centres where demand exceeds supply in the VMAT technique planning systems, the use of 3D teletherapy over IMRT/VMAT could continue to be used in patients with stage IIB to IIIC1.

HPV genotyping of cervical histologic specimens of 61, 422 patients from the largest women hospital in China.

Objectives: We investigated HPV genotypes in a large cohort of patients with definitive cervical histologic diagnosis. Methods: HPV testing was performed by real-time PCR assay, including 18 high-risk HPV (hrHPV) and 3 low-risk HPV (lrHPV). Totally 61,422 patients with documented HPV genotyping results within 6 months before cervical histologic diagnoses were included. Results: HrHPV positive rate was 55.1% among all tested cases with the highest in adenosquamous carcinoma (94.1%), followed by squamous cell carcinoma (SCC) (93.7%), cervical intraepithelial neoplasia 2/3 (CIN2/3) (92.8%). HrHPV positive rates were significantly higher in high-grade squamous lesions than in those in glandular lesions. HPV16 was the most common genotype followed by HPV52 and HPV58 in CIN2/3. The most frequent hrHPV genotype in adenocarcinoma in situ (AIS) was HPV18, followed by HPV16, HPV45 and HPV52. In SCC cases, HPV16 was the most common type followed by HPV58, HPV52, HPV18 and HPV33. However, HPV18 showed significantly higher prevalence in adenocarcinoma and adenosquamous carcinoma than in that in SCC. Theoretically, the protective rates of 2/4-valent and 9-valent vaccine were 69.1% and 85.8% for cervical cancers. Conclusions: The prevalence of HPV genotypes in Chinese population was different from that in Western population. Some hrHPV types were identified in cervical precancerous lesions and cancers, which are not included in current HPV vaccines. These data provide baseline knowledge for future HPV vaccine development.

A Large Exophytic Tumor of the Cervix Causing Vaginal Bleeding in Pregnancy: A Case Report.

Vaginal bleeding in the second and third trimesters of pregnancy is usually due to placental causes, namely placental abruption and placenta previa. Other causes include uterine rupture, vasa previa, and hematologic disorders. However, benign or malignant lesions of the vagina and the cervix may also cause vaginal bleeding or spotting. Although cervical cancer in pregnancy is rare, about 8% of pregnant women have an abnormal Pap smear and 3% of the total cervical cancers are diagnosed during pregnancy. We report a case of a 20-week pregnant woman who presented with vaginal bleeding; a visual inspection revealed a large exophytic lesion of the cervix. The Pap smear demonstrated a low-grade squamous intraepithelial lesion (LSIL) related to human papillomavirus (HPV) infection. The differential diagnosis based on the findings of the colposcopy included invasive cervical carcinoma, warty lesions, and perishable lesion. A cesarean section and the removal of the cervical tumor were scheduled and carried out as planned at 37 weeks of gestation. The histologic examination showed extensive lesions of low-grade squamous intraepithelial cervical neoplasia (LSIL/CIN1). Despite the fact that exophytic tumors of the cervix are extremely rare, in women presenting with vaginal bleeding or spotting during the second or third trimester of pregnancy, the ultrasound scan must be followed by a visual inspection of the vagina and the cervix.

Real-world effectiveness of HPV vaccination against cervical neoplasia among birth cohorts ineligible for routine vaccination.

Human papillomavirus (HPV) vaccine effectiveness may differ between settings. Here we present the first real-world effectiveness study of HPV vaccination on high-grade cervical lesions from Norway, among women who received HPV vaccine outside the routine program. We performed an observational study of all Norwegian women born 1975 to 1996 and retrieved individual data from nationwide registries on HPV vaccination status and incidence of histologically verified high-grade cervical neoplasia during 2006 to 2016. We estimated the incidence rate ratio (IRR) and 95% confidence intervals (CI) for vaccination vs no vaccination by Poisson regression stratified by age at vaccination <20 years and ≥20 years. The cohort consisted of 832 732 women, of which 46 381 (5.6%) received at least one dose of HPV vaccine by the end of 2016. The incidence rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) increased with age regardless of vaccination status and was highest at age 25 to 29, at 637/100 000 among unvaccinated women, 487/100 000 among women vaccinated before age 20 and 831/100 000 among women vaccinated at age 20 or older. The adjusted IRR of CIN2+ between vaccinated and unvaccinated women was 0.62 (95% CI: 0.46-0.84) for women vaccinated below age 20, and 1.22 (95% CI: 1.03-1.43) for women vaccinated at age 20 or older. These findings indicate that HPV vaccination among women too old to be eligible for routine HPV vaccination is effective among women who are vaccinated below age 20 but may not have the desired impact among women who are vaccinated at age 20 or older.

Extended human papillomavirus genotype distribution in cervical intraepithelial neoplasia and cancer: Analysis of 40 352 cases from a large academic gynecologic center in China.

Our aim was to conduct a large epidemiologic analysis of the distribution of human papilloma virus (HPV) genotypes associated with cervical neoplasias and cancers at a major Chinese gynecologic center. The pathologic database was searched for cervical histopathologic diagnoses with prior HPV genotyping from liquid cervical cytology specimens obtained ≤6 months before biopsy. HPV testing was performed by using the Tellgenplex HPV27 or YanengBio HPV23 genotyping assays. A total of 40 352 cases meeting study criteria were identified. High risk human papillomavirus (hrHPV) was detected in 94.1% of squamous cancers compared to in only 83.3% of cervical adenocarcinomas. The prevalence of multiple HPV infections was highest in cervical intraepithelial neoplasia 1 (CIN1) (33.8%) and decreased with increasing severity of squamous lesions. The distribution of HPV genotypes was similar between CIN1 and histopathologic-negative cases. HPV16 was one of the three most common hrHPV genotypes before all histopathologic abnormalities, ranging from 72.0% for cervical cancers, 38.7% for CIN2/3/AIS, 13.1% for CIN1, and 9.1% for biopsy-negative cases. HPV16 and HPV18 accounted for over 87.2% of detected hrHPV genotypes for all glandular intraepithelial neoplastic lesions and cancers, whereas squamous lesions did not show this pattern. 80.3% of cervical cancers were associated with genotypes covered by HPV16/18 vaccines and 89.6% with genotypes covered by 9-valent vaccination.

Cervical neoplasia in relation to socioeconomic and demographic factors - a nationwide cohort study (2002-2018).

INTRODUCTION: Cervical cancer is a major cause of mortality and morbidity. We aimed to estimate the association between sociodemographic factors and cervical neoplasia. MATERIAL AND METHODS: In this Swedish nationwide open cohort study, 4 120 557 women aged ≥15 years at baseline were included between January 1, 2002 and December 31, 2018. The two outcomes were cervical cancer and carcinoma in situ identified in the Swedish Cancer Register. Sociodemographic factors (age, education level, family income level, region of residency, country of origin) were the main predictors. Incidence rates per 10 000 person-years were calculated. Cox regression was used to estimate hazard ratios. Sensitivity analyses were conducted, including parity, urogenital infections, alcohol- and drug-use disorders, and chronic obstructive pulmonary disease (used as a proxy for tobacco abuse). RESULTS: In 38.9 million person-years of follow-up, 5781 (incidence rate: 1.5, 95% confidence interval [CI] 1.4-1.5) and 62 249 (incidence rate 16.9, 95% CI 15.9-16.1) women were diagnosed with cervical cancer and carcinoma in situ, respectively. Women from Eastern Europe had a hazard ratio of 1.18 (95% CI 1.05-1.33) for cervical cancer compared with Swedish-born women, while women from non-Western regions were inversely associated with cervical cancer and carcinoma in situ. Women with a low education level had a hazard ratio of 1.37 (95% CI 1.29-1.45) for cervical cancer compared with women with a high education level. CONCLUSIONS: Women from the Middle East and Africa living in Sweden seem to suffer less from cervical neoplasia, whereas women with low education and women from Eastern Europe seem to suffer more from cervical cancer.

The interplay between HPV, other Sexually Transmissible Infections and genital microbiome on cervical microenvironment (MicroCervixHPV study).

Background: The importance of Cervicovaginal Microbiota in protecting against infections (such as HPV) is already well established, namely through Lactobacillus spp., as well as the mechanism through which HPV leads to Cervical Neoplasia. However, it is not possible to classify HPV as a complete carcinogen. Thus, the importance of exploring Cervicovaginal dysbiosis with the intention of deciphering this interaction with HPV, takes on greater relevance. The main objectives of this study were: 1) Comparison of the MCV composition of women with or without HPV and women with ASCUS or LSIL; 2) Characterization of cytokines present in the vaginal microenvironment; 3) Evaluation of the blood count ratios as prognostic systemic inflammatory biomarkers; 4) Correlation between MCV, HPV serotypes and cytokines. Methods: This was a retrospective, observational, multicenter, cross-sectional study. CVM analysis was performed by isolation RNA and sequencing on a NGS platform. Cytokine concentrations of CVM were obtained through Multiplex platform. Statistical analysis was performed in SPSS v 26.0. An α of 0.05 was considered statistically significant. Results: Highlighting the core of the study, CVM types of CST I and CST IV were found to influence the emergence of cervical lesions. Neutrophil-to-Lymphocyte ratio was found to impact the prognosis of ASCUS. Within CVM, Lactobacillus prevent the growth of other CST IV species, while the latter express symbiotic relationships with each other and show affinity for specific HPV serotypes. At last, RANTES chemokine is significantly elevated in cervicovaginal infections. Conclusion: The importance of using vaginal cytokine profiles and CVM is highlighted in the hypothesis of prevention of Cervical Neoplasia development, as well as in its use as a prognostic biomarker. Taken together, these insights are one step closer to personalized medicine.

Molecular Epidemiology of Human Papillomavirus Infection Among Chinese Women With Cervical Cytological Abnormalities.

Background: Virtually all invasive cervical cancers are caused by persistent genital human papillomavirus (HPV) infection. Therefore, HPV-based screening becomes an essential tool as one of the cervical prevention strategies to reduce the disease burden. Population-specific epidemiologic information on HPV infection among women with cytological abnormalities is essential to inform the strategy of HPV-based screening programme. The study also explored the presence of cutaneous HPV types (Beta-ß and Gamma-γ) in cervical infections. Methods: A cross-sectional study on Chinese women aged ≥25 years who were referred to public specialist out-patient clinics for colposcopy or further management of cervical cytological abnormalities were recruited between 2015 and 2016 in Hong Kong. HPV was detected and typified by the novel PCR-based Next-Generation Sequencing (NGS) strategies. Results: The overall HPV infection rate was 74% and detected in 222 of the 300 respondents, with the prevalence of cutaneous HPV infection being 2.3%. The overall prevalence of HPV infection among women with current cytological abnormalities was 79.1% (197/249). The age-specific prevalence of HPV (any-type HPV infection) among women with cytological abnormalities reached the first peak with 87.9% in the age group of 35-39 years and gradually declined to 56.0% at 55-59 years. While a second peak occurred at 65 years or above (92.9%). HPV58 (13.7%), HPV52 (11.7%), HPV53 (11.2%), HPV16 (10.0%), HPV18 (5.2%), and HPV51 (5.2%) were the top five high-risk HPV genotypes among women with cytological abnormalities. Any-HPV type infection was significantly associated with an abnormal cervical smear (OR = 3.7; 95% CI 2.0-7.1), and high-risk HPV infection was also significantly associated with an abnormal cervical smear (OR = 6.3; 95% CI 3.0-13.5). Conclusion: New evidence on the second peak of HPV infection at ≥65 years old suggests the necessity to review the current guideline for the cervical screening program extending to age 65 and above. Moreover, the high prevalence of two HPV genotypes-high-risk HPV51 and potential high-risk HPV53, among women with cytological abnormalities-suggests further research work is needed to confirm the contributory role of HPV51 and HPV53 in cervical cancer and the need for inclusion in the next generation of the HPV vaccine.

Increased detection of high grade CIN, when using electrical impedance spectroscopy as an adjunct to routine colposcopy, is maintained when used across international boundaries: Prospective data from nine European countries.

OBJECTIVE: To evaluate the performance of EIS (ZedScan) with colposcopy in the detection of high grade CIN (HG-CIN) in different health care settings. METHOD: Pooled analysis of data from 26 colposcopy centres in 9 countries. All women underwent colposcopy and ZedScan examination. Data was recorded prospectively via a proforma. Indications for referral to colposcopy were according to national guidelines. Pathology was reported according to national guidelines. RESULTS: 5257 women were examined by 82 colposcopists, median 93 women per centre (range 41 - 2684), 3 users per centre (range 1-8). Referral indications were; 19.3% high grade cytology, 50.4% low grade, 30.3% clinical or HPV positive / cytology negative. The prevalence of HG-CIN was 26.5%; 79.1% in high grade referrals, 16.7% low grade, 9.4% clinical or HPV positive / cytology negative. The use of ZedScan detected an extra 269 cases of high grade CIN (24% increase) (7.5% increase for high grade referrals, 57.9% for low grade and 52% for clinical or HPV positive/cytology negative). Based upon colposcopic impression (CI), the sensitivity of colposcopy for CIN2 + was 74.1% compared with 91.6% for colposcopy with ZedScan (Chi2 p < 0.0001). The PPV for a ZedScan directed biopsy varied according to referral cytology and colposcopic impression (19.5% to 85.7%). 489 women underwent treatment at first visit, when ZedScan suggested treatment, 95.1% had HG-CIN/HG-CGIN or cervical cancer. The pooled results for the whole 26 centres were consistent with the results obtained for the largest centre (Sheffield) alone and also with the results with this largest centre excluded. CONCLUSIONS: The addition of EIS (ZedScan) increases detection of HG-CIN with the PPV for a ZedScan directed biopsy consistent with the published literature. Results were similar in multiple healthcare settings. With more women being referred to colposcopy at low risk of HG-CIN, due to HPV vaccination and primary HPV screening, this study confirms the value of a real time adjunctive technology.

Evaluation of effectiveness, acceptability and safety of thermal ablation in the treatment of cervical neoplasia in Burundi.

This longitudinal study aimed at evaluating the effectiveness, acceptability and safety of the thermal ablation procedure (TA) in the treatment of cervical neoplasia. Women referred to the Gynaecology ward for symptoms or for opportunistic screening were assessed by visual inspection with acetic acid (VIA) and colposcopy. Those with lesions eligible to ablation were counselled and treated by TA. They were inquired about the level of pain during the procedure, and their level of satisfaction. Patients were followed up at 6 weeks for any complication and reassessed by VIA and colposcopy at 12 months for any persistent or recurrent lesion and for any adverse event. A total of 86 women with a positive VIA test were included in the study. The mean age was 46 years (28-61 years). Most of the women did not complain about any adverse event during treatment; one-third presented mild pain or cramp. At the 6-week visit, watery discharge was the main adverse event reported. All women were highly satisfied with TA and most of them would recommend it. At the 12-month visit, 82 women were examined (95% follow-up rate), and the overall cure rate was 96% (low-grade lesions: 98%; high-grade lesions: 94%). Three women presented low- and high-grade lesions that were treated by TA. No major adverse event or hospitalisation after the treatment was reported. In conclusion, TA was an effective procedure with a high cure rate at the 1-year follow-up visit. It was acceptable and safe, with only minor short-term side-effects reported and with a high satisfaction rate among the patients.

A literature review on correlation between HPV coinfection with C. trachomatis and cervical neoplasia - coinfection mediated cellular transformation.

Cervical cancer is the fourth most common cause of mortality worldwide. Persistent infection with high-risk human papillomaviruses (hrHPV) is a known significant risk factor in cervical neoplasia development (CN). Though HPV contributes to carcinogenesis, other factors provide an ideal niche for persistence of HPV, especially, coinfection with Chlamydia trachomatis (CT) which has been linked to CN development. CT infection is associated with inflammation, cell proliferation, EMT transition and anti-apoptotic processes. To better understand the correlation between HPV-CT coinfection and CN development, a literature review was conducted on the prevalence of HPV-CT coinfection focusing on the role of infection-induced inflammation as HPV-CT coinfection creates an environment for cellular transformation, activates an innate immune response and triggers EMT transition. Moreover, inflammation plays a crucial role in developing neoplasia as there is a decrease in effector cells and a change in the levels of players like ROS and miRs. CT infection induces chronic inflammation followed by cervical epithelial cell damage and increases susceptibility to HPV infection which may lead to cellular transformation. The literature search was performed based on a comprehensive investigation of publications in the PubMed journal database and Scopus, on the development of CN. We have reviewed the prevalence of HPV-CT infection and the factors increasing the risk of developing CN.

Preventing Uterine Cervix Cancer: The Clinical Meaning of Atypical Glandular Cells / Prevenção do câncer do colo uterino: Significado clínico das células glandulares atípicas

Abstract Objective To determine the prevalence of the atypical glandular cells (AGCs) cytology and to analyze its clinical significance in different age ranges. Methods Retrospective observational study using computerized data from the Brazilian National Cancer Institute, including women screened between January 2002 and December 2008. The women included were those with an AGC result who were properly followed-up with colposcopy and a second cytology. Results A total of 132,147 cytopathological exams were performed during the study period. Five-hundred and thirty-three (0.4%) women with AGC cytology were identified and, of these, 69.41% (370/533) were properly referred for colposcopy and a new cytology. Most of the women (79.2%) with a 1st or 2nd AGC cytology were between the ages of 25 and 54 years. The 2nd cytology demonstrated 67.6% (250/370) of normality, 24.5% (91/370) of squamous atypia, and 6.2% (23/370) of AGC, 0.8% (3/370) adenocarcinoma in situ and 0.8% (3/370) adenocarcinoma invasor. On biopsy of the women with a second AGC cytology, 43.4% (10/23) had normal histology, 43.4% (10/23) had squamous lesions, 8.7% (2/23) had invasive adenocarcinoma, and 1.2% (1/23) had an inconclusive report. All of the women with high-grade squamous intraepithelial lesion (HSIL) or invasive adenocarcinoma (respectively 5 and 2 patients), after a 2nd AGC cytology were 25 years old or older. Conclusion The prevalence of the AGC cytology was low in the studied population. Most of the AGC cytology cases occurred in adult women between the ages of 25 and 54. Although most of the patients had normal histology after follow-up, several of them presented with squamous intraepithelial lesions or invasive adenocarcinoma.

Resumo Objetivo Determinar a prevalência de citologia com laudo de células glandulares atípicas (AGCs, na sigla em inglês) e analisar a significância clínica nas diferentes faixas etárias Métodos Estudo observacional retrospectivo, usando os dados arquivados no sistema do Instituto Nacional de Câncer no Brasil, que incluiu mulheres rastreadas entre janeiro de 2002 a dezembro de 2008. As mulheres incluídas tinham citologia com resultado de AGCs, que foram acompanhadas com colposcopia e nova citologia Resultados Um total de132,147 exames citopatológicos foram incluídos durante o período de estudo. Quinhentas e trinta e três mulheres com citologia de AGC foram identificadas e destas, 69.41% (370) foram encaminhadas para colposcopia e nova citologia. A prevalência de citologia de AGC na população estudada foi 0.4%. A maioria das mulheres (79.22%) com resultado citológico de AGC tinham idade entre 25 e 54 anos. A segunda citologia demonstrou 67.56% (250/370) de normalidade, 24.5% (91/370) de atipias escamosas, e 6.2% (23/370) de AGC. Na biopsia das mulheres com a 2ª citologia de AGC, 43.4% (10/23) tinham histologia normal, 43.4% (10/23) tinha lesões escamosas, 8.7% (2/23) tinha adenocarcinoma invasor e 1.2% (1/23) tinha laudo inconclusivo. Todas as mulheres com lesões intraepiteliais escamosas de alto grau (HSIL, na sigla em inglês) ou adenocarcinoma invasor (respectivamente 5 e 2pacientes), após a 2ª citologia com AGC, tinham 25 anos de idade ou mais. Conclusão A prevalência de citologia com AGC foi baixa na população estudada. Muitos casos de citologia com AGC apareceram em mulheres adultas, entre 25 e 54 anos de idade. Embora a maioria das pacientes tiveram histologia normal após seguimento, várias apresentaram lesões intraepiteliais escamosas ou glandulares invasoras.

Effectiveness of Visual Inspection with Acetic Acid (VIA) Screening on Cervical Cancer Mortality and Incidence - A Systematic Review and Meta-Analysis.

OBJECTIVES: Despite being a cheap, easy, and commonly used technique for screening early development of cervical cancer, collective evidence on the effect of visual inspection with acetic acid (VIA) for reducing cervical cancer mortality and incidence are conflicting. We conducted a systematic review and meta-analysis to determine the effectiveness of VIA screening on cervical cancer mortality and incidence. METHODS: We searched PubMed, Embase, Cochrane library (Cochrane Database of Systematic Reviews & Cochrane Central Register of Controlled Trials), World Health Organization's (WHO) International Clinical Trials Registry Platform, and Google Scholar to identify studies conducted among women with no history of cervical cancer that assessed effectiveness of VIA on the cervical cancer mortality and incidence. Random effects model was used to estimate incident rate ratio and sensitivity analysis was conducted using Bayesian methods. RESULTS: Of the included 4 studies, three were cluster randomized trials from India and one was quasi-experimental study done in Thailand. Duration of follow-up ranged from 7 to 12 years. Based on 3 trials, pooled rate-ratio for cervical cancer mortality and all-cause mortality was 0.68 (95% CI: 0.56-0.81, I2=0%) and 0.91 (0.85-0.97, I2=57%), respectively. Pooled rate-ratio of invasive cervical cancer was 0.94 (95% CI: 0.67 - 1.30, I2=84%). Likewise, there was non-significant reduction in incidence of stage IB, >=stage II, and unknown stage cervical cancer. CONCLUSIONS: VIA screening may lead to reduction in cervical cancer and all-cause mortality in long run. However, the effectiveness of VIA in preventing invasive cervical cancer is inconclusive.

The detection of cervical neoplasia via optical imaging: a pilot clinical study.

PURPOSE: The present study aims to develop a new high-resolution imaging system for the early diagnosis of cervical neoplasia based on increased vessel density of the cervical tissue. METHODS: An optical device was developed to obtain high contrast and resolution images of vascular structures of the cervix in the present study. The device utilizes a telecentric lens to capture cervix images under light illumination with a wavelength of 550 nm emitted from LEDs. Images were obtained using the telecentric lens with or without acetic acid application to the cervix. Image processing algorithms were used to contrast and extract the skeleton of the vascular structures on the cervix. In the evaluation of the vascular density, the cervical images were divided into 12 o'clock positions, and the fractal dimension of the vascularity was calculated for each dial area between the o'clock positions. The region with the largest fractal dimension was accepted as the region with the highest probability of lesion. The range of vessel sizes was split into small classes of "bins" for each dial area with the highest fractal dimension. To validate the system's success in differentiating between normal and HSIL lesions, forty five patients who underwent colposcopy and biopsy were included in a pilot study. RESULTS: The system correctly classified four HSIL cases out of five and failed to detect one HSIL case, achieving an accuracy rate of 97.8% with an 80% sensitivity and 100% specificity. CONCLUSION: The developed high-resolution optical imaging system may potentially be used in detecting cervical neoplasia just before the biopsy and reduce the number of false-positive cases.