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Introduction: We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women. Methods: These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-yearold HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy. Results: Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Discussion: Long-term follow-up of randomized, initially adolescent HPVvaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer. [ABSTRACT FROM AUTHOR]

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 a 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 highrisk 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 populationwas 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

La inmunosupresión es un factor de riesgo conocido para el cáncer de cérvix uterino. Las mujeres con enfermedades reumáticas están inmunosuprimidas por la enfermedad de base y los tratamientos recibidos. Uno de los principales factores de riesgo consiste en no acudir al programa de detección precoz del virus del papiloma humano. Los objetivos de este trabajo fueron evaluar la adherencia al programa de cribado de pacientes seguidas en consultas externas de reumatología, así como estudiar la prevalencia de lesiones cervicales y su asociación con distintos aspectos de la enfermedad y los tratamientos recibidos. Estudio retrospectivo en el que se revisaron las historias clínicas electrónicas de pacientes con seguimiento activo en un hospital terciario con artritis reumatoide, artritis psoriásica y lupus eritematoso sistémico. Se incluyó 307 pacientes. No se hallaron datos de asistencia al cribado en 42,4% (39,6% en artritis reumatoide, 43,8% en artritis psoriásica y 46% en lupus eritematoso sistémico). Entre las pacientes que asistieron al menos una vez (57,6%), la prevalencia de displasia de cérvix fue del 5,1%. No se encontró ningún caso de neoplasia. En el análisis de regresión logística simple no se encontró asociación entre las variables recogidas y la presencia de infección y displasia. Es remarcable la ausencia de datos de asistencia al cribado de cáncer de cérvix en un porcentaje considerable de las pacientes con enfermedades reumáticas, lo cual dificulta el estudio del papel de la enfermedad y su tratamiento. Immunosuppression is a known risk factor for cervical cancer. Women with rheumatic conditions are immunosuppressed due to the disease and the treatments. One of the main risk factors for this neoplasm is the lack of adherence to early detection programmes for human papillomavirus. The objectives of this study were to evaluate the adherence to the screening programme of patients in the Rheumatology Clinic, as well as to evaluate the prevalence of cervical lesions and their association with the different disease characteristics and the treatments received. A descriptive retrospective study. The electronic medical history of patients actively being followed up in a tertiary hospital with rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus were reviewed. Finally, 307 patients were included. No data were found for screening programme attendance in up to 42.4% of the patients (39.6% in rheumatoid arthritis, 43.8% in psoriatic arthritis and 46% in systemic lupus erythematosus). Among the patients who attended the screening programme at least once (57.6%), the prevalence of cervical dysplasia was 5.1%. No cases of neoplasia were found. In the simple logistic regression analysis, there was no association between attending the screening programme and any variable. The study also showed no association between the variables collected and the presence of infection and dysplasia. These results are influenced by the absence of screening data in a significant percentage of patients and by the low prevalence of dysplasia found in this series of patients with rheumatic diseases. [ABSTRACT FROM AUTHOR]

Objectives: With the perspective of prophylactic vaccination against high‐risk human papillomavirus (HPV), we analyzed the viral epidemiology of cervical neoplasia in Senegal. Methods: All patients were treated at the Institut Joliot Curie du Cancer in Dakar. HPV genotypes were characterized using a real‐time polymerase chain reaction‐based approach and sequencing. Results: Histologically, there were 224 invasive carcinomas, 17 high‐grade intraepithelial neoplasia (CIN), and five undetermined histologies. Molecular analysis was conclusive in 241 cases. HPV DNA was found in 207/241 (85.9%) cases while 34/241 (14.1%) remained HPV negative. There was one single genotype in 127/207 (61.4%) cases and several in 80/207 (38.6%) corresponding to 308 genotypes identified. Viral genotyping found HPV16 in 175 (56.8%) cases, HPV18 in 45 (14.6%), HPV45 in 40 (13.0%), HPV58 in 35 (11.4%), HPV33 in 6 (2.0%), HPV35 in 3 (1.0%), HPV31 in 2 (0.6%), HPV39 and HPV56 in one (0.3% each). Conclusion: Our analysis showed that 98.4% of the HPV‐positive cases were associated with viral genotypes covered by the 9‐valent HPV vaccine. However, 14.1% of cases remained HPV negative. Therefore, prophylactic vaccination using a 9‐valent vaccine should dramatically reduce the incidence of HPV‐associated neoplasia but the detection and treatment of CIN remain necessary for the optimal prevention of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: High-risk human papillomavirus (HR-HPV) are responsible for cervical cancer (CC) which represents the second most prevalent gynecological cancer among Tunisian women. Preventive strategies against CC are based on prophylactic vaccines that have not yet been implemented into the national vaccination program of Tunisia. Therefore, the present study aimed to investigate the HPV genotypes distribution in cervical neoplasia in Tunisian women in order to predict the impact of using current HPV vaccines on cancer prevention in Tunisia. Methods: A total of 200 formalin-fixed paraffin embedded biopsies were collected in our study. DNA was extracted using Qiagen Mini prep kit. DNA quality was controlled by Beta Globin PCR. Only positive samples for Beta Globin test were used. HPV detection was performed by a nested PCR using PYGMY and GP5+/6+ primers. Genotyping was performed by Reverse Line hybridization using 31 probes. Results: The mean age of participants was 38.97 years and 75% were over 30 years. Cervical neoplasia distribution according to age showed that CINII/CINIII was observed among women over 30 years old. All samples were positive for Beta Globin PCR. Overall HPV prevalence in cervical lesions was 83% (166/200). HPV was present in 65% of CINI, 82% of CINII/CINIII and 85% of CC. HR-HPV was statistically significantly associated with cervical intraepithelial neoplasia (p < 10–3). HR-HPV distribution according to lesion grade and cervical cancer showed that HPV16 and HPV18 were present in all lesions. For CINII/CINIII, HPV 35 (37.5%) was the most detected type, followed by HPV18 (33.3%) HPV 45 (28.5%) and HPV 16 (18.9%). HPV 45(57.5%), HPV 18 (53.3%) were the most detected in CC. HPV58, 59, 68 were only detected in CC and associated with HPV45, 18 and HPV16. HPV39, 31, 33, 52, 56 and HPV70 was associated only with CINI. Conclusions: Our findings can give useful information for vaccine implementation by helping the health policymakers to choose the most appropriate vaccine type in Tunisia. [ABSTRACT FROM AUTHOR]

The purpose of this review was to examine and summarize data for inosine pranobex (IP) immunotherapy in cervical HPV-positive patients. Persistent or recurring cervical human papillomavirus (HPV) infection is a major cause of cervical cancer. Self-clearance and blocking of cervical HPV infection depend on the status of the host immune system. Immunotherapy helps accelerate elimination of the infection. Host immunity is involved in the development of HPV infection. Several mechanisms of interaction between the virus and the immune system have been revealed; however, the mechanisms have not been completely elucidated. A properly functioning immune system impedes HPV progress and helps clear the pathogen from the body. IP has antiviral efficacy because it modulates both cellular and humoral immunities. IP has been on the market since 1971. Nevertheless, it has seldom been administered to treat cervical HPV infections. In this review, Google Scholar, PubMed/MEDLINE, Scopus, Cochrane Library, and Research Gate were searched for the period 1971– 2021. Prospective controlled trials, observational and retrospective studies, and meta-analysis and reviews on immunotherapy against HPV cervical infection were explored. Prior studies showed strong clinical efficacy of combined and standalone IP therapy in reversing HPV-induced changes in the cervix, preventing disease progression, and clearing the pathogen. IP treatment enhanced host antiviral activity against HPV, delayed or stopped cervical oncogenesis, and rapidly removed HPV from the body. [ABSTRACT FROM AUTHOR]

Background: Understanding the source of newly detected human papillomavirus (HPV) in middle-aged women is important to inform preventive strategies, such as screening and HPV vaccination.Methods: We conducted a prospective cohort study in Baltimore, Maryland. Women aged 35-60 years underwent HPV testing and completed health and sexual behavior questionnaires every 6 months over a 2-year period. New detection/loss of detection rates were calculated and adjusted hazard ratios were used to identify risk factors for new detection.Results: The new and loss of detection analyses included 731 women, and 104 positive for high-risk HPV. The rate of new high-risk HPV detection was 5.0 per 1000 woman-months. Reporting a new sex partner was associated with higher detection rates (adjusted hazard ratio, 8.1; 95% confidence interval, 3.5-18.6), but accounted only for 19.4% of all new detections. Among monogamous and sexually abstinent women, new detection was higher in women reporting ≥5 lifetime sexual partners than in those reporting <5 (adjusted hazard ratio, 2.2; 95% confidence interval, 1.2-4.2).Conclusion: Although women remain at risk of HPV acquisition from new sex partners as they age, our results suggest that most new detections in middle-aged women reflect recurrence of previously acquired HPV. [ABSTRACT FROM AUTHOR]

This clinical study was developed to primarily evaluate the Complete Cytopathological Response Rate of Cervical Intraepithelial Neoplasms to PDT using chitosan nanocapsules containing Chlorocyan-aluminum phthalocyanine as a photoactive agent. Analyses of the Free Recurrence Interval, toxicity profile (immediate and late), and complications (immediate and late), were secondarily analyzed. This study was previously approved by the National Council of Ethics in Research of Brazil (CONEP), on May 28, 2014, under case number 19182113.4.0000.5009. On the surface of the cervix of each selected patient was applied one mL of the formulated gel, and after 30 min, the light was applied. Reports or the identification of adverse effects and/or complications were observed in follow-up visits, in addition to the collection of cervical oncotic cytology. Out of the total group, 11 (91.7%) primarily treated patients evolved with negative cervical oncotic cytology as soon as in the first evaluation following treatment, and one did not achieve any therapeutic benefit, even after reapplication. Two patients with initially positive response presented cytological recurrence determined by histopathology. A new round of PDT was developed, and both evolved with cytological remission three weeks later, remaining negative until the last follow-up. No important side effects were observed in all the patients. Our trial demonstrates that treatment of CIN 1 and 2 lesions using our PDT formulation is feasible and safe. Large randomized clinical trials are required to establish efficacy. [ABSTRACT FROM AUTHOR]

High-risk human papillomaviruses (hrHPVs) are causally related to cervical intraepithelial neoplasia (CIN) and subsequent cervical cancer (CC). The vaginal microbiome has been suggested to play a role in the development of CC, but the effect of conservative surgical treatment on the microbiome and hrHPV elimination has not been elucidated. In this study, we aimed to characterize the vaginal microbiome and inflammatory chemokine profile in 85 women treated for CIN2-CIN3 lesions, before and after surgical CIN removal. The results showed, as expected, a high prevalence of dysbiotic microbiomes and vaginal pro-inflammatory cytokines in the CIN cohort, correlated with disease severity, at the basal level. By contrast, surgical CIN removal induced significant vaginal microbiome variations, and specific microbiome/cytokine profiles were associated with hrHPV clearance/persistence at 6-month follow-up. hrHPV-cleared patients, in fact, showed a specific increase of L. crispatus and decrease of dysbiosis and inflammatory cytokines compared to hrHPV-persistent patients. These data highlight the crosstalk between HPV and the local microbiome, and suggest that vaginal microbiome modulation might represent a novel approach to modifying the natural history of hrHPV-related CC. Study registration n. ISRCTN34437150 (https://www.isrctn.com/ISRCTN34437150). [ABSTRACT FROM AUTHOR]

Objective: To establish the prevalence of high-grade cervical intraepithelial neoplasia (CIN2+) in women referred to colposcopy with persistent high-risk human papillomavirus (hrHPV) cytology-negative screening sample according to hrHPV genotype, age at referral and colposcopic performance.Design: Prospective cohort study.Setting: Single colposcopy clinic linked to a population-based screening programme.Population: Women referred with persistent hrHPV cytology-negative routine screening samples.Methods: Prospective study with descriptive statistics from a single colposcopy unit between June 2014 and July 2019.Main Outcome Measures: Prevalence of hrHPV genotypes and CIN2+, positive predictive value for colposcopic impression, and inadequate colposcopic examinations.Results: A total of 3107 women were referred. Prevalence of CIN2+ was highest for persistent HPV16 infections (10.7%) compared with HPV18 (3.6%) or HPVO (4.7%). Prevalence of CIN2+ declined with age (25-34 years 14.2% to 55-64 years 1.1%) whereas the percentage of women with an inadequate colposcopic examination increased (25-34 years 0.9% to 55-64 years 29.5%). High-grade colposcopic impression fell over time during the study from 16.1 to 5.1%. The positive predictive value for colposcopic impression of CIN2+ was affected by hrHPV genotype (57.3% for HPV16 versus 32.1% for nonHPV16). The adjunctive use of electrical impedance spectroscopy detected an extra 42 cases of CIN2+, which was irrespective of hrHPV genotype.Conclusions: Primary hrHPV cervical screening increases detection of CIN2+; however, low specificity results in more women being referred to colposcopy with a low prevalence of CIN2+. Colposcopy performs poorly in some groups, particularly with HPVO infections and women over 50 years of age. An appropriate threshold for referral to colposcopy in primary hrHPV screening has not been established.Tweetable Abstract: Low prevalence of CIN2+ in HPV-positive negative cytology samples. HPV genotype, age and prevalence of CIN2+ affect colposcopic performance. [ABSTRACT FROM AUTHOR]

Objective: HIV infection increases the risk of high-grade cervical neoplasia and invasive cervical carcinoma. The study addresses the limited data describing human papillomavirus (HPV) infection and cervical neoplasia among HIV-infected women in HIV-discordant relationships in sub-Saharan Africa, which is needed to inform screening strategies.Methods: A cross-sectional study of HIV-infected women with HIV-uninfected partners was conducted to determine the distribution of type-specific HPV infection and cervical cytology. This study was nested in a prospective cohort recruited between September 2007 and December 2009 in Nairobi, Kenya. Cervical cells for HPV DNA testing and conventional cervical cytology were collected. HPV types were detected and genotyped by Roche Linear Array PCR assay.Results: Among 283 women, the overall HPV prevalence was 62%, and 132 (47%) had ≥1 high-risk (HR)-HPV genotype. Of 268 women with cervical cytology results, 18 (7%) had high-grade cervical lesions or more severe by cytology, of whom 16 (89%) were HR-HPV-positive compared with 82 (41%) of 199 women with normal cytology (p<0.001). The most common HR-HPV types in women with a high-grade lesion or more severe by cytology were HPV-52 (44%), HPV-31 (22%), HPV-35 (22%), HPV-51 (22%) and HPV-58 (22%). HR-HPV genotypes HPV-16 or HPV-18 were found in 17% of women with high-grade lesions or more severe. HR-HPV screening applied in this population would detect 89% of those with a high-grade lesion or more severe, while 44% of women with normal or low-grade cytology would screen positive.Conclusion: HR-HPV prevalence was high in this population of HIV-infected women with an uninfected partner. Choice of screening for all HR genotypes versus a subset of HR genotypes in these HIV-infected women will strongly affect the performance of an HPV screening strategy relative to cytological screening. Regional and subpopulation differences in HR-HPV genotype distributions could affect screening test performance. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is essential for developing cervical cancer and precancerous lesions. Currently, three vaccines are available, which are effective as prophylaxis against HPV infection, however, limited knowledge exists about the possible effect of vaccinating women treated with conization to prevent recurrence. The aim of our study was to examine the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after conization according to HPV vaccination status. Using Danish nationwide registries, we identified women diagnosed with CIN3 on the cone (2006–2012) and their HPV vaccination status. Vaccinees were defined as women vaccinated between 3 months before until 1 year after conization. The women were followed from 1 year after conization until diagnosis of CIN2+, conization, death, emigration or end of follow‐up. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of CIN2+ comparing vaccinees with nonvaccinees. The HR was adjusted for age, histology on cone, education, year of conization, repeat conizations and CIN2+ lesions between conization and start of follow‐up. Altogether 17,128 women were included (2,074 vaccinees). There was a statistically nonsignificant lower risk of CIN2+ among vaccinees (HRadjusted = 0.86, 95% CI: 0.67–1.09). Women vaccinated 0–3 months before tended to have a slightly lower HR of CIN2+ (HRadjusted = 0.77, 95% CI: 0.45–1.32) than women vaccinated 0–12 months after conization (HRadjusted = 0.88, 95% CI: 0.67–1.14), although not statistically significantly different. Our results add to the current knowledge about the potential clinical effect of vaccination as an adjunct to conization of high‐grade cervical neoplasia to decrease risk of recurrence. What's new? Vaccination against human papillomavirus (HPV) is an effective means of preventing cervical cancer in healthy women. Whether HPV vaccine can also prevent cervical malignancy in women previously treated with conization to remove abnormal cervical tissue, however, remains unknown. Here, women who received HPV vaccine three months before until one year after conization were found to have a marginally lower subsequent risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), relative to unvaccinated women. While the results did not reach statistical significance, they suggest that HPV vaccination may be beneficial for women who have undergone conization. [ABSTRACT FROM AUTHOR]

Objectives: Cervical cancer is rated fourth in terms of incidence and cancer-related mortality in women. Cytology-based screening programs and colposcopy provided insufficient rates of detecting cervical intraepithelial neoplasia (CIN) prompting researchers to develop new tools. The aim of this study was to evaluate whether folate receptor-mediated staining is useful in detecting CIN2+ during gynecological examination with colposcopy. Material and methods: In total 96 women with abnormal cytology findings were enrolled. The study was conducted on the Polish population. The diagnostic process consisted of colposcopy, receptor-mediated diagnosis (FRD), and histopathology examination. All women were subjected to the same diagnostic procedure. Results: The patient mean age of 96 women was 38 ± 14.5 years. On colposcopy, high-grade lesions were detected in 83 women. The FRD gave positive results in 63 women. Histopathology revealed 1 case of carcinoma plano epithelial akeratodes, 21 cases of high-grade squamous intraepithelial lesions, 13 cases of low-grade squamous intraepithelial lesions. A total of 61 cases presented no pathology. FRD as an adjunct to colposcopy gave the following test results in detecting CIN2+ lesions: sensitivity -- 94.29%, specificity -- 46.67%, PPV -- 50.77%, NPV -- 93.33%, and accuracy -- 64.21%. Using both techniques provided better results than using each of the tests alone. Conclusions: FRD is a promising test for the diagnosing CIN2+ cervical pathologies because it can increase the probability of detecting CIN2+ without any additional burden posed on patients. Further studies should be conducted on large and various populations to complement current evidence. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer has become a major public health challenge in developing countries with a reported age-standardised incidence rate of about 17.9/100,000/year and lifetime risks approaching 1 in 20 in some settings. Evidence indicates that HIV-seropositive women are 2 to 12 times more likely to develop precancerous lesions that lead to cervical cancer than HIV-negative women. There is a lack of rigorous evidence on which treatment methods are being utilised for HIV-positive women, and this review aims to synthesise available evidence on treatment modalities for both cervical neoplasia and cervical cancer in HIV-seropositive women in developing countries. Methods: A systematic review guided by a published protocol was conducted. Online databases including MEDLINE/PubMed, Embase, CINAHL and Emerald (via EBSCOhost), PsycINFO, Cochrane Library, and health databases, which cover developing countries (3ie Systematic Reviews, WHO library and databases, World Bank website), were searched for published articles. Additional articles were found through citation, reference list tracking, and grey literature. Study design, treatment category, geographic country/region, and key outcomes for each included article were documented and summarised. Results: Thirteen research articles from sub-Saharan Africa, Asia, and South America were included. Eight (61.5%) articles focused on the treatment of cervical cancer with the remaining five (38.5%) assessed cervical neoplasia treatment. The available cervical cancer treatments, radiotherapy, chemotherapy, chemoradiation, and surgery are effective for HIV-seropositive patients, and these are the same treatments for HIV-negative patients. Both cryotherapy and LEEP are effective in reducing CIN2+ among HIV-seropositive women, and a choice between the treatments might be based on available resources and expertise. Radiation, chemotherapy, concurrent treatment using radiotherapy and chemotherapy, and surgery have shown the possibility of effectiveness among HIV-seropositive women. Cervical cancer stage, immunosuppressive level including those on HAART, and multisystem toxicities due to treatment are associated with treatment completion, prognostic, and survival outcomes. Conclusions: Treatment of cervical cancer is based on the stage of cancer, and poor outcomes in most developing countries might be due to a lack of optimal treatment regimen. Those infected with HIV were younger and had advanced cervical cancer as compared to those who were HIV-negative. Facilitation and putting HIV-infected people on life-long ART is of importance and has been found to have a positive impact on cervical cancer treatment response. Research on precancerous lesions and cervical cancer management of HIV-seropositive patients focusing on the quality of life of those treated; the effectiveness of the treatment method considering CD4+ count and ART is required. Systematic review registration: PROSPERO CRD42018095707 [ABSTRACT FROM AUTHOR]

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Objective: There are currently three licensed human papillomavirus (HPV) vaccines that protect against cervical cancer. Here we compare the prevalence of bi-, quadri-, and nonavalent vaccine-related HPV genotypes in a multi-ethnic sample of non-Hispanic white, non-Hispanic black, Hispanic, and Asian women. Design: Patients in this analysis (n = 419) represent a subset of women with a previous abnormal Pap test participating in a clinical trial. HPV genotyping was conducted using the Roche Linear Array. Prevalent HPV genotypes were grouped according to their inclusion in each of the vaccines: bivalent (16, 18), quadrivalent (16, 18, 6, 11), and nonavalent (16, 18, 31, 33, 45, 52, 58, 6, 11). Results: The prevalence of HPV genotypes covered by the bi-/quadrivalent vaccines was lowest among non-Hispanic black (15%) and Hispanic women (20%), compared to non-Hispanic white (38%) and Asian women (38%). Across all racial/ethnic groups, a large proportion of infections (38%–49%) were with genotypes included in the nonavalent vaccine. However, the prevalence of HPV genotypes not covered by any vaccine was significantly higher among non-Hispanic black (36%) and Hispanic women (42%), compared to non-Hispanic white (24%) and Asian women (16%) (p < 0.001). Racial/ethnic differences in HPV genotype prevalence were observed when controlling for demographic and sexual behavior characteristics, as well as when restricting the analysis to women with CIN 2+. Conclusion: Our data suggest racial/ethnic differences in the prevalence of vaccine-related HPV genotypes. In particular, non-Hispanic black and Hispanic women had the lowest prevalence of HPV genotypes covered by the bi-/quadrivalent vaccines. While a large proportion of their infections were covered by the nonavalent vaccine, non-Hispanic black and Hispanic women also had the highest prevalence of HPV genotypes not covered by any vaccine. [ABSTRACT FROM AUTHOR]

HPV 16 and HPV 18 infection is 10.6% and 5.9%, respectively, while women who are With high-risk HPV infection who had no further HPV And HPV 16 or HPV 18 infection using multinomial logis- Abbreviations: HPV, human papillomavirus; OR, odds ratio; aOR, adjusted odds ratio; CI, confidence interval. [Extracted from the article]

Background: Most endocervical adenocarcinomas are human papillomavirus (HPV)-related cancers associated with p16 immunostaining. Ovarian metastasis from cervical cancer is a rare phenomenon, the mechanism of dissemination remains unclear. The diagnosis of metastasis may be difficult to establish when the ovarian neoplasm presents features consistent with primary tumor. Immunohistochemical expression of p16 in ovarian tumors can guide the diagnosis of metastasis from HPV-related cervical cancer, but p16 positivity is nonspecific. Identical HPV genotype in the paired endocervical and ovarian tumors is a better marker for cervical origin, which may also be confirmed by identical HPV integration site.Case Presentation: Two women presented with HPV18 cervical adenocarcinoma. No signs of disease were visible on MRI after treatment. After several years of follow-up, mucinous ovarian tumors were discovered in both patients. Molecular analyses showed that the ovarian lesions were HPV18-positive; indicating a primary cervical origin. A third woman was diagnosed with grade 1 ovarian endometrioid carcinoma with no peritoneal carcinomatosis. Final histological examination and HPV genotyping revealed HPV18-related in situ endometrioid adenocarcinoma in the endocervix and HPV18-related invasive endometrioid adenocarcinoma in the endometrium and both ovaries. Additional molecular analyses performed in two patients identified the same HPV integration sites in both the ovarian and cervical tumors, confirming that the ovarian mass was a metastasis from the cervical adenocarcinoma.Conclusion: We report three new cases of ovarian neoplasia in which the diagnosis of metastasis from cervical cancer was supported by the same HPV genotype and the same integration site in the paired cervical and ovarian tumors. To our knowledge, this is the first report of molecular evidence of the cervical origin of an ovarian metastasis. HPV screening should be performed in ovarian tumors for all patients with history of cervical neoplasia. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is essential in cervical carcinogenesis, however, less is known about the carcinogenic potential of individual HPV types. Our aim was to examine the risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) after persistence of 13 individual oncogenic HPV types. Liquid‐based cervical samples (n = 40,399) collected in 2002–2005 were tested for HPV by hybrid capture 2 and genotyped with INNO‐LiPAv2. Persistence was defined as having the same genotype twice 1–4.5 years apart. The absolute risk of CIN3+ was estimated by the Aalen‐Johansen estimator and Cox proportional hazard regression was used to compare the rates of CIN3+ according to HPV type adjusting for age and time between HPV tests. Of 2,875 oncogenic HPV‐positive women, 874 had persistence of one or more types and 761 persisted for one oncogenic HPV type only. Persistent HPV16 infection was associated with the highest risk of CIN3+, with an 8‐year absolute risk of 55% (95% CI: 45%–66%), followed by HPV33 (33% (95% CI: 20%–50%)), HPV18 (32% (95% CI: 20%–48%)) and HPV31 (31% (95% CI: 21%–46%)). Other HPV types, including HPV52 and HPV45, were also associated with high risks. Persistent HPV56 had the lowest 8‐year absolute risk of CIN3+ (3% (95% CI: 0.4%–20%)). In Cox analyses, a similar pattern remained after adjustment for age and time between tests. Our results add knowledge about the varying carcinogenic potential of individual persistent oncogenic HPV types, which may have implications for the clinical use of HPV testing. What's new? While the critical role of human papilloma virus (HPV) infection in cervical cancer is well established, less is known about the cancer risk associated with individual HPV subtypes. Here the authors performed a large population‐based study including 40,000 Danish women. They show large differences in absolute risk for high‐grade cervical intraepithelial neoplasia (CIN3+) development linked to persistent infection with 13 oncogenic HPV types. They suggest that these differences may inform clinical use of type‐specific HPV testing in the future. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to evaluate the frequency of human papillomavirus (HPV) in the oral cavity of women with and without abnormal cervical cytology and to determine whether there is an association of oral HPV infection with infection of the cervix or with cervical cancer precursor lesions.Methods: The present study was conducted among 406 women, aged 18-82 years, who attended the Prevention Department of Barretos Cancer Hospital (HCB), Brazil due to a previous altered cervical cytology result. Oral rinse, cervical cytology and biopsy were collected at the same day. The participants also answered a questionnaire about socioeconomic characteristics and risk factors for cervical cancer. Molecular screening for HPV16, HPV18 and 12 other high-risk HPV types was performed on cervical and oral rinse specimens using Cobas 4800 (Roche Molecular Systems, USA).Results: HPV was detected in the oral rinse of 3.9% of participants. Infection of the oral cavity with a non-HPV16 or 18 type was most frequent (81.2%), followed by HPV16 (18.7%). Infection with HPV in the cervix and oral cavity was present in 11 (2.7%) of participants. There were no differences observed in the smoking status (p value 0.62), mean age of first sexual intercourse (p value 0.25), mean age of the first oral sex (p value 0.90) or mean lifetime number of sexual partners (p value 0.08) between the participants with oral HPV infection or not.Conclusion: The presence of HPV infection in the oral cavity was low in the group of women with abnormal cervical cancer screening findings and a high rate of cervical HPV infection. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk.Methods: Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13858 healthy controls of European decent.Results: The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10-9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10-8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10-9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10-5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006).Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism. [ABSTRACT FROM AUTHOR]

Introduction: Sexually Transmitted Diseases (STDs) are very common in the sexually active young Indian women particularly in rural areas because of poor genital hygiene. Aim: The present study was carried out to compare the prevalence of different STDs in the urban and rural population of Lucknow, Uttar Pradesh. Materials and Methods: The present prospective observational study was conducted in 2369 rural women attending camps in 126 villages of West Lucknow between May 2013 and March 2017 undergoing cervical cancer screening and in 38,478 urban women attending Gynaecology Outpatient Department (OPD) of KG Medical University, Lucknow, Uttar Pradesh, India, between April 1971 to November 2005 in which the data were collected retrospectively. Statistical analysis was performed with SPSS version 18.0 and the results were subjected to chisquare test. Results: The incidence of Candida albicans was higher in rural women (4.7%) as against 1.1% seen in urban cohorts. The trend was reverse with Trichomonas vaginalis, the incidence being high (2.9%) in the Urban women than 1.0% in the rural group. The viral STDs were rarely seen in both the groups ranging from 0.1% to 0.6%. Association of Squamous Intraepithelial Lesions (SILs) of the cervix with non-viral STDs was more pronounced in rural women than in their urban counterparts while this was very high with viral STDs in both the groups. All the STDs except HSV were commonly seen in younger sexually active women between 21-30 years. Leucorrhoea was commonly associated with all STDs in both groups but the incidence was almost double in rural women. Conclusion: All the STDs examined were commonly seen in younger women between 21-30 years mostly with symptoms of leucorrhoea. Hence, cytological screening is felt mandatory in such women to rule out any STD infection. [ABSTRACT FROM AUTHOR]

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Objective: Vaginal self-sampling for human papillomavirus (HPV) testing has recently been proposed to optimize cervical cancer screening coverage. The objective of this study was to compare the performance of self-taken samples using flocked and cotton swabs for HPV detection and cellular retrieval. Methods: We recruited women aged 21–65 years, referred to colposcopy at the Division of Gynecology of the Geneva University Hospitals between May and September 2016. Each participant collected 2 vaginal samples: 1 with a cotton swab and 1 with a flocked swab. A 1:1 randomization determined the order in which the 2 samples were taken. The swabs were introduced into a 20 mL PreservCyt® vial. Real-time polymerase chain reaction analysis using the Anyplex™ II HPV HR assay, cytofluorometric analysis and cytological cell counting were performed on each sample. Results: A total of 119 participants were recruited in the study. Their mean ± standard deviation age was 35.1±8.9 years. The HPV prevalence was 29.7% and 38.1% according to the cotton and flocked swab, respectively (p=0.006). The mean number of cells collected per milliliter according to cytofluorometry was 96,726.6 with the cotton swab and 425,544.3 with the flocked swab (p,0.001). The mean number of cells detected at cytological cell count was 13,130.42 using the cotton swab and 17,503.6 using the flocked swab (p,0.001).Conclusion: The flocked swab achieved a greater cellular retrieval and showed an improved performance in HPV detection. Further studies are needed to assess the usability and cost-effectiveness of the 2 self-sampling devices [ABSTRACT FROM AUTHOR]

Background: The interactions of oral contraceptive (OC) use, risk of human papillomavirus (HPV) infection and associated cellular atypia are complex. We investigated the association between history of OC-use, and cytological or histopathological abnormalities in a cohort of non-HPV vaccinated originally 16-17-year-old women participating the PATRICIA trial for 4 years.Methods: The total number of hepatitis A-virus (control) vaccine recipients participating in the clinical PATRICIA trial in Finland was 2399. Nine-hundred and ninety-nine women returned questionnaires on living conditions-life habits and sexual health after completing the study. Mean age at answering the questionnaire at the end of the clinical trial was 22 years. Age at sexual debut varied between 12 and 16 years for majority of the women. Cervical cytological samples were obtained every 6 months throughout the PATRICIA trial. The relative risk of cervical atypia associated with time since start of oral contraceptives use was calculated as odds ratio (OR) with 95% confidence interval (CI) using logistic regression.Results: Compared to never-users, the smoking and age-at-sexual-debut adjusted relative risk of cervical intraepithelial neoplasia grade 1 (CIN1) in women who had started the use of oral contraceptives for more than 1 year was low (OR 0.2, 95% CI: 0.1-0.7). Risk of cytological atypia was also reduced (OR 0.6) albeit not significantly (95% CI: 0.3-1.3).Conclusions: Use of oral contraceptives does not increase the risk of cervical atypia but when established might instead be protective. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer is the third most common cancer in India. In women, it is the second most common after breast carcinoma. Human cancers arise from a protracted sequence of multiple genetic and epigenetic alterations which involve the growth regulatory genes like p53. Aim: This study aimed at correlation of immunopositivity of p53 with the histopathological type and grade of carcinoma cervix. Materials and Methods: A total of 100 cases of cervical biopsy/ hysterectomy specimens of carcinoma cervix received at the Department of Pathology, SMSMC Jaipur from January 2016 to September 2017 were examined for gross and microscopic features. Immunohistochemistry was used to study the p53 expression as proliferative index in cervical intraepithelial neoplasia, invasive squamous cell carcinoma as well as adenocarcinoma of the uterine cervix. Results: The demographic profile of SCC and CIN in this study was in concordance with that described by epidemiological studies in India with larger group of patients presenting with advanced stage tumors. Increased expression of p53 was found in increasing grades of CIN and SCC. The p53 positivity showed a statistically significant association with squamous cell carcinoma (SCC) histologic type (P = 0.005). Conclusion: The expression of p53 is greater in the malignant cervical neoplasms than pre-malignant cervical lesions, suggesting that p53 overexpression can be used as an early diagnostic tool and also as a prognostic indicator. [ABSTRACT FROM AUTHOR]

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Introduction: Conservative treatments including cold knife cone biopsy (CKC) or loop electrosurgical excision procedure (LEEP) are fertility-preserving alternatives to hysterectomy. The risks of persistent cervical neoplasia in women with negative surgical margins following conservative treatment of adenocarcinoma-in-situ (AIS) are uncertain. This study aims to investigate the risk of persistent or recurrent cervical neoplasia [AIS, adenocarcinoma and/or high-grade cervical squamous intraepithelial neoplasia (CIN)] and compliance with follow-up recommendations in conservatively treated women with AIS and negative histopathological margins.Material and Methods: A retrospective, population-based study of Western Australian women treated by CKC or LEEP for AIS between 2001 and 2012. Histopathology reports were reviewed for demographic information, treatment procedures and clinicopathological factors. Primary outcomes were the diagnosis of cervical neoplasia during follow-up (defined as <12 months) and surveillance (≥12 months) periods.Results: The cohort comprised 360 women, with 175 (48.6%) initially treated by CKC and 185 (51.4%) treated by LEEP. The median patient age at time of excisional treatment was 30.0 years (range 18-64 years) and the median follow-up time was 3.9 years (range six months to 12.2 years). During the follow-up and surveillance periods, seven (1.9%) women were diagnosed with CIN 2/3, 10 (2.8%) with AIS, and one (0.3%) with cervical adenocarcinoma, despite their initial excision specimens having negative histological margins.Conclusion: In this study, there was a low but significant risk of persistent or recurrent cervical neoplasia in women who had initial conservative management of AIS with negative histopathological margins. [ABSTRACT FROM AUTHOR]

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The second leading cause of death in women worldwide is the cervical cancer, being an important public health issue. The aim of the paper was to evaluate the prevalence of cervical neoplasia and the treatment used for this pathology. We included a total of 111 cases diagnosed with cervical neoplasia. The cervical cancers are found more frequently in women on perimenopause and menopause. In our study, the stage I or the carcinoma in situ were treated by conization or hysterectomy. The type of interventions for the other stages (I B, II A and II B) were radical hysterectomy and bilateral adnexectomy. In 79 (71.17%) cases the intervention was radical Wertheim hysterectomy (with pelvic lymphadenectomy). We also identified 3 (2.70%) cases of stage IIIA, IIIB or IV where it was performed an exploratory laparotomy. Cervical cancer can be detected relatively easily by screening, indicated especially at the women at high risk, through a gynecological examination, vaginal cytology and HPV genotyping. The prognosis is favorable in cases detected in the early stages, and unfavorable in the advanced ones, so, it is dependent on the breakthrough stage, the woman's age, histopathological form and the combination of therapeutic approach to the task. [ABSTRACT FROM AUTHOR]

Background:  Uptake of human papillomavirus (HPV) vaccine in the United States is slow, and the effectiveness of the vaccine has not been assessed in high-risk adolescent populations.Methods:  We conducted a longitudinal study of 1139 sexually active, inner-city adolescent women receiving the 3-dose quadrivalent (4vHPV) vaccine. Cervical and anal specimens collected semiannually were tested using an L1-specific polymerase chain reaction assay. Postvaccination incidence of 4vHPV vaccine and nonvaccine HPV types, and risk of cervical cytological abnormalities, were assessed in relation to time to completion of all 3 vaccine doses.Results:  Compared to vaccine naive women at enrollment, vaccinated women had significantly lower incidence rate ratios of cervical infection with HPV6/11/16/18 (0.2; 95% confidence interval [CI], .1-.4) and the related types HPV31 and HPV45 (0.4 [95% CI, .2-1.0] and 0.3 [95% CI, .1-.6], respectively), as well as significantly lower incidence rate ratios of anal infection with HPV6/11/16/18 (0.4; 95% CI, .2-.7). Notably, we observed higher risks of cervical HPV6/11/16/18 infection (hazards ratio [HR], 2.9; 95% CI, 1.0-8.0) and associated cytological abnormalities (HR, 4.5; 95% CI, .7-26.0) among women immunized at ≥15 years of age who took ≥12 months (vs <12 months) to complete the 3-dose regimen.Conclusions:  Among adolescents immunized at ≥15 years of age, a longer time to complete the 3-dose schedule was associated with an increased risk of anogenital HPV6/11/16/18 infection and an increased incidence of associated cervical cytological abnormalities. [ABSTRACT FROM AUTHOR]

Cervical neoplasia is one of the most prevalent malignant neoplasms worldwide. Ribonucleotide reductase 1 (RRM1) is thought to play an essential role in modulating the development and progression of cervical neoplasia. Two novel genetic polymorphisms, RRM1 −756T>C and −269 C>A, are significantly correlated with RRM1 expression. Some epidemiological studies have demonstrated that genetic variants play a crucial role in susceptibility to cervical cancer. The present study aimed to identify the genetic polymorphisms RRM1 −756T>C and −269 C>A in patients with cervical neoplasia and healthy controls. In total, 493 subjects, comprising 324 healthy controls and 169 patients with cervical neoplasia, were enrolled for this study. The allelic discrimination of the RRM1 −756T>C (rs11030918) and −269C>A (rs12806698) polymorphisms was assessed using the ABI StepOne™ real-time polymerase chain reaction system and analyzed using Software Design Specification (SDS), Version 3.0, software with TaqMan assays. The risk of cervical cancer was examined, revealing adjusted odds ratios and 95% confidence intervals of 1.25 [0.51, 3.08] and 1.09 [0.43, 2.78] for individuals with CC alleles of RRM1 −756T>C and for individuals with AA alleles of RRM1 −269C>A genetic polymorphisms, respectively, compared to individuals with wild-type RRM1 genetic polymorphisms. No significant genetic interaction effect was observed in susceptibility to cervical neoplasia, and no association was found between genetic polymorphisms and clinical statuses of invasive cervical cancer. The genetic polymorphisms RRM1 −756T>C and −269C>A may not be a factor for susceptibility to cervical neoplasia. [ABSTRACT FROM AUTHOR]

Little is known about the incidence and risk of cervical intraepithelial neoplasia (CIN) grade 3, adenocarcinoma in situ and invasive cervical cancer (CIN3+) among migrants living with HIV in a European setting. We assessed the cumulative incidence (CuI) and hazard ratio (HR) of CIN2+ and CIN3+ in a cohort of women living with HIV (WLWH) ( n = 893) identified from the Swedish national HIV register and HIV-negative women ( n = 205,842) identified from the Swedish Population Register, matched on region of birth and age. Data was collected between 1993 and 2011 by linking our cohort with the Swedish National Cervical Screening Registry, collecting all cytological and histological results since 1993. The CuI of CIN3+ was 13.1% [95% confidence interval (CI) 8.9-17.2] for WLWH and 2.1% (95% CI 2.0-2.2) for HIV-negative after 18 years of follow-up. WLWH had more than eight times higher, age and region of birth matched, risk of CIN3+ than HIV-negative (HR 8.8: 95% CI 6.9-11.3). WLWH born in the East region, dominated by Thai women, had a two times higher risk of CIN3+ compared with WLWH born in Sweden (HR 2.47: 95% CI 1.2-5.0), which remained after adjusting for immunosuppression. Our results showed a substantially increased risk of CIN3+ among WLWH, which differed depending on birth region. Early HIV diagnosis and attendance to cervical cancer screening, with focus on migrants, is of crucial importance to minimize the incidence of cervical intraepithelial neoplasia. [ABSTRACT FROM AUTHOR]

Aim of the study: To evaluate the diagnostic capacity of tele-cervicography for the detection of cervical neoplasia as an adjunctive test with Papanicolaou (Pap) smears. Material and methods: Pap smear and tele-cervicography were performed on each subject. Histologic results were obtained for all patients. Results: Of the 863 females who had a tele-cervigram, 252 (29.2%) had a positive result. Of the 60 histologically confirmed cases of high-grade squamous intraepithelial lesions (HSILs), 56 (93.3%) were detected by tele-cervicography, including 16 (26.7%) with a positive grade of 1 and 40 (66.7%) with a positive grade of 2. With the positive threshold of tele-cervicography set as any positive grade (P0 to P3), the overall sensitivity was 94.0% (95% CI: 88.0-97.3%), the specificity was 80.9% (95% CI: 80.0-81.5%), and the positive likelihood ratio was 4.94 (95% CI: 4.23-5.77) for the detection of HSILs or cancer. The combination of tele-cervicography with Pap smear testing for the detection of HSILs or cancer resulted in an increase in sensitivity from 84.6% (Pap only: cutoff = atypical squamous cells of undetermined significance or more severe) to 98.3% (Pap plus tele-cervicography: cutoff = P0 or more severe). Conclusions: The sensitivity of tele-cervicography was higher than that of cytology for the detection of cervical neoplasia, and combining the two tests increased the sensitivity. Tele-cervicography can be considered a useful complementary tool to cytology. [ABSTRACT FROM AUTHOR]

The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR = 0.60; 95 % CI = 0.38-0.95; p = 0.029; CA+AA vs CC genotype: OR = 0.60; 95 % CI = 0.39-0.93; p = 0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR = 0.55; 95 % CI = 0.32-0.93; p = 0.034) by 50 %, representing a protective factor against the development of more severe cervical lesions. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the association between Toll-like receptor 2 (TLR2) gene polymorphisms and human papillomavirus (HPV)-related cervical neoplasia in Korean women.Material and Methods: Peripheral blood samples collected from 127 patients with HPV-related cervical neoplasia and 175 healthy women were genotyped for the TLR2 -16934, +1350, intron1, and 3' untranslated region (UTR) polymorphisms using the polymerase chain reaction and restriction fragment length polymorphism method.Results: The TLR2 -16934 A/A, intron1 A/A, and +1350 T/C genotypes were more frequent in patients than in controls [odds ratio (OR) = 2.1, 95% CI = 1.302-3.475, p = 0.002; OR = 1.9, 95% CI = 1.168-3.169, p = 0.010; and OR = 1.9, 95% CI = 1.211-3.123, p = 0.006, respectively]. The frequencies of the TLR2 + 1350 C and 3'UTR G alleles were also higher in patients (OR = 2.0, 95% CI = 1.236-3.121, p = 0.004 and OR = 1.7, 95% CI = 1.005-3.076, p = 0.046, respectively). The genotype frequencies of TLR2 -16934 A/A and intron1 A/A increased with increasing oncogenic risk of the HPV genotype, as follows. low-risk type < high-risk type < HPV-16 and/or HPV-18 type (p = 0.008).Conclusions: Our study provides the first evidence that TLR2 gene polymorphisms are associated with high-risk type HPV-related cervical neoplasia and may play an important role in susceptibility to HPV infection. Further large-scale and functional studies are needed to confirm the role of TLR2 gene polymorphisms in HPV-related cervical neoplasia. [ABSTRACT FROM AUTHOR]

Background: Precursors to anal squamous cell carcinoma may be detectable through screening; however, the literature suggests that population-level testing is not cost-effective. Given that high-grade cervical neoplasia (CIN) is associated with an increased risk of developing anal cancer, and in light of changing guidelines for the follow-up and management of cervical neoplasia, it is worthwhile to examine the costs and effectiveness of an anal cancer screening program delivered to women with previously-detected CIN.Methods: A model of anal cancer screening and treatment was constructed, to estimate the cost-effectiveness of a population of CIN II/III+ women who were screened using anal cytology vs. one that received no anal cancer screening. Costs were based on Canadian estimates, and survival was based on estimates taken from the scientific literature. Effectiveness was measured in terms of life years gained (LYG) and quality-adjusted life years (QALYs). The model was run for 50 cycles, with each cycle representing one year.Results: Incremental cost (screened vs. unscreened) was $82.17 per woman in the model. Incremental effectiveness was 0.004 LYG, and was equivalent to zero in terms of QALY. An ICER of $20,561/LYG was calculated, while no meaningful incremental cost-effectiveness ratio (ICER) could be calculated for quality-adjusted survival.Conclusion: Our analysis suggests that anal cancer screening is cost-effective in terms of overall survival in women with a previous diagnosis of CIN II or CIN III as part of regular follow-up, but may not contribute meaningfully-different quality-adjusted survival due to the adverse effects of screening-related interventions. [ABSTRACT FROM AUTHOR]

HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/μL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer. [ABSTRACT FROM AUTHOR]

Background: In the past, cervical cancer has been linked to Human Papilloma Virus (HPV) infection. Previously, we found that pre-neoplastic breast and ovarian lesions may be associated with lamin A/C deficiency, resulting in abnormal nuclear morphologies and chromosomal instability. Ultimately, these phenomena are thought to lead to cancer. Here, we assessed lamin A/C deficiency as an indicator for the risk to develop cervical cancer. Methods: The expression of lamin A/C was assessed by Western blotting in cervical uterine smears (CUS) of 76 adult women from Benin concomitant with nuclear morphology assessment and HPV genotyping using microscopy and PCR-based assays, respectively. In vitro analyses were performed to uncover the mechanism underlying lamin A/C expression alterations observed in vivo. The presence of cervical intra-epithelial neoplasia (CIN) was assessed by colposcopy. Results: Normal lamin A/C expression (group A) was observed in 39 % of the CUS, weak lamin A/C expression (group B) was observed in 28 % of the CUS and no lamin A/C expression (group C) was observed in 33 % of the CUS tested. Infection with oncogenic HPV was found to be significantly higher in group C (36 %) than in groups A (17 %) and B (14 %). Two years after our first assessment, CIN was observed in 20 % of the women in group C. The in vitro application of either a histone deacetylase inhibitor (trichostatin) or a protein kinase inhibitor (staurosporine) was found to restore lamin A/C expression in cervical cancer-derived cells. Conclusion: Lamin A/C deficiency may serve as an independent risk factor for CIN development and as an indicator for preventive therapy in cervical cancer. [ABSTRACT FROM AUTHOR]

Cervical cancer development has been mainly associated with persistent human papillomavirus (HPV) infections. However, HPV infection is unlikely to be sufficient to cause cervical cancer, and the contribution of other sexually transmitted infections (STIs) could be the determining factor for cervical lesion-progression. The aim of this study was to estimate the prevalence of STIs associated with HPV-positivity in 201 cervical samples from patients who underwent annual routine gynecological exams. The overall prevalence of STIs was 57.7%, and the most frequent infection was Ureaplasma spp (UP) (39.8%), followed by Gardnerella vaginalis (GV) (25.9%), α-HPV (18.4%), Chlamydia trachomatis (CT) (1.5%), and Mycoplasma genitalium (MG) (0.5%). The highest prevalence rate of multiple non-HPV infections was observed for the age-range 31-40; for papillomavirus infection, the age-range was 21-30. In normal cervical samples, HPV16 was the most prevalent genotype (24.3%), followed by genotypes 58 (13.5%) and 52 (10.8%). Intriguingly, HPV18 was not detected in the study population, and genotypes 52 and 58 were found exclusively in samples with abnormal cytology. Papillomavirus infection with oncogenic types was significantly associated with GV ( P = 0.025) and strongly associated with multiple non-HPV pathogens ( P = 0.002). The following variables correlated significantly with cytological diagnosis of low-grade squamous intraepithelial lesion (LSIL): GV ( P = 0.028), multiple non-HPV infections ( P = 0.001), and high-risk HPV positivity ( P = 0.001). Epidemiological data from this study will contribute to the molecular detection of sexually transmitted pathogens from screening programs to identify those women who are at risk for developing cervical lesions. J. Med. Virol. 87:2098-2105, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to critically examine the literature and present a comprehensive model of three pathways through which IPV increases the risk for cervical cancer. The first pathway is increased exposure to cervical cancer risk factors among IPV victims, including smoking, psychosocial stress, risky sexual behaviors, and sexually transmitted infections (STDs/STIs), particularly human papillomavirus infection. The second pathway is poor compliance with cervical cancer screening. The third pathway is delay/discontinuation in treatment for cervical dysplasia and neoplasia. Control imposed by the abusive partner, competing life priorities, and limited access to financial/support resources restrict a woman's ability to seek cancer services. Higher rates, severity, and duration of IPV among low-income, Black, and Hispanic women may explain the pervasive cervical cancer disparities. [ABSTRACT FROM AUTHOR]