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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]

IntroductionWe 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.MethodsThese 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-year-old 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.ResultsOverall, 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.DiscussionLong-term follow-up of randomized, initially adolescent HPV-vaccinated 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.

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]

BackgroundThe 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.MethodsThis 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.ResultsHighlighting 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.ConclusionThe 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.

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) 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. [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]

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. [ABSTRACT FROM AUTHOR]

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.

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]

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]

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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Abstract Objective To analyze the quantity of cervical smears, also designated Papanicolaou tests, between 2006 and 2015 in all the Federal units of Brazil, as well as to verify the quantity of exams collected outside the recommended age range and the economic impact of such excess. Methods The data was collected from the Ministry of Health’s database called Sistema de Informação do Câncer do Colo de Útero (SISCOLO), which contains all the test results collected nationwide by the Unified Health System (SUS, in the Portuguese acronym). From that, the number of exams and the age range of thewomen who underwent them were analyzed; besides, these numbers were stratified according to the state of where the exam was performed. The quantity of exams collected outside the recommended age range was verified, and, so, the economic impact generated was noted. Results Between 2006and2015, 87,425,549Papanicolaoutestswere collected in Brazil. Of these, 20,215,052 testswere collected outside the age range recommended by the Brazilian Ministry of Health; this number corresponded to 23.12% of all exams. From such data, considering that each Pap smear collected by SUS generates a cost of BRL 7.30 to the government, according to the information in the Tabela SUS dated September 2018, there was a total charge of BRL 147,569,880 for tests collected outside the protocol. Conclusion In Brazil, according to the Ministry of Health’s protocol about the recommended practices on collecting Pap smears, whose newest edition dates of 2016, it is recommended that Pap smears are collected inwomen from a specific age range, inwhom the potential diagnosing advantages overcome the onus of overdiagnosis or of a lesion with great regression potential. However, such protocols have not been correctly followed, promoting more than 20 million tests in excess, and an exorbitant cost for the Brazilian public health system. It is relevant to take measures to correctly use the official protocol, reducing the patients risks, as well as the economic impact for SUS.

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]

• HPV vaccination and primary HPV screening have been shown to be effective. • Women at low risk of high grade CIN are now being referred to colposcopy. • Colposcopy performs poorly when there is a low prevalence of high grade CIN. • ZedScan increases the detection of high grade CIN across multiple centres. To evaluate the performance of EIS (ZedScan) with colposcopy in the detection of high grade CIN (HG-CIN) in different health care settings. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Abstract 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

Stefan Miladinov Kovachev Department of Gynecology, Military Medical Academy, Sofia, BulgariaCorrespondence: Stefan Miladinov KovachevDepartment of Gynecology, Military Medical Academy, G. Sofiisky str. 3, Sofia, 1404, BulgariaTel +359888902314Email stkovachev@abv.bgAbstract: 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.Keywords: cervical neoplasia, clearance, humoral immunity, innate immunity, oncogenesis, inosine pranobex

BackgroundVirtually 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-β and Gamma-γ) in cervical infections.MethodsA 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.ResultsThe 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).ConclusionNew 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.

We investigated the influence of pathology data to improve patient outcomes in the treatment of high-grade cervical neoplasia in a joint pathology and gynecology collaboration. Two of us (B.S.D. and M.D.) reviewed all cytology, colposcopy and surgical pathology results, patient history, and pregnancy outcomes from all patients with loop electrosurgical excision procedure specimens for a 33-month period (January 2011-September 2013). We used this to determine compliance to 2006 consensus guidelines for the performance of loop electrosurgical excision procedure and shared this information in 2 interprofessional and interdisciplinary educational interventions with Obstetrics/Gynecology and Pathology faculty at the end of September 2013. We simultaneously emphasized the new 2013 guidelines. During the postintervention period, we continued to provide follow-up using the parameters previously collected. Our postintervention data include 90 cases from a 27-month period (October 2013-December 2015). Our preintervention data include 331 cases in 33 months (average 10.0 per month) with 76% adherence to guidelines. Postintervention, there were 90 cases in 27 months (average 3.4 per month) and 96% adherence to the 2013 (more conservative) guidelines (P < .0001, χ2 test). Preintervention, the rate of high-grade squamous intraepithelial lesion in loop electrosurgical excision procedures was 44%, whereas postintervention, there was a 60% high-grade squamous intraepithelial lesion rate on loop electrosurgical excision procedure (P < .0087 by 2-tailed Fisher exact test). The duration between diagnosis of low-grade squamous intraepithelial lesion and loop electrosurgical excision procedure also increased significantly from a median 25.5 months preintervention to 54 months postintervention (P < .0073; Wilcoxon Kruskal-Wallis test). Postintervention, there was a marked decrease of loop electrosurgical excision procedure cases as well as better patient outcomes. We infer improved patient safety, and higher value can be achieved by providing performance-based pathologic data.

Objectives 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. Methods 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. Results 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. Conclusions 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 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

Objectives: To explore the population-based risk factors for genital herpes in women and examine whether genital herpes occurs at higher rates in women diagnosed with cervical neoplasia and common urogenital infections., Methods: An open cohort study consisting of 4,097,075 women ≥15 years of age in Sweden (2002-2018). The outcome was genital herpes diagnosis. The predictor variables were sociodemographic factors (age, educational level, family income, region of residence, and country of origin) and urogenital comorbidities (cervical carcinoma neoplasia, cystitis, vaginosis, and vulvovaginitis) and parity. National registers and primary health care data were used. Cox regression models were used to estimate hazard ratios with 95% confidence intervals. Interactions tests were conducted., Results: A total of 15,727 women received a genital herpes diagnosis in inpatient and outpatient specialist care settings during the study period. Sociodemographic factors and parity were associated with genital herpes. than women without these comorbidities., Conclusions: Genital herpes occurs with higher rates in women of high family income, young age, Swedish origin, co-occurrence of urogenital comorbidities, and nulliparity. The findings can be used by clinicians when encountering women with these risk factors., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Aim To examine the relationship between tumor differentiation, parametrial, and lymphovascular invasion, as well as the differential expression pattern of cyclooxygenase-2 (COX-2) in cervical intraepithelial neoplasia and various forms of cervical cancer. Methods Histologically diagnosed cases of in-situ and malignant lesions of the cervix were included in the study. Two sections were cut from paraffin blocks. One section was stained with Haematoxylin and Eosin (H&E) for morphologic diagnosis, and the other sections were subjected to COX-2 immunohistochemical staining. Cases of colon carcinoma were taken as positive controls. Cytoplasmic and membrane staining of tumor cells were considered as positive staining, and grading was done. Results Out of the 62 patients, 40 cases (64.5%) showed positive expression of COX-2 in squamous cell carcinoma when compared to in-situ cervical intraepithelial neoplasia and adenocarcinoma. The results were statistically significant, with a p-value of 0.003. Conclusion COX-2 expression is directly proportional to the level of grading of the tumor. The higher the grading, the higher the expression of COX-2. Selective COX-2 inhibitors increase the efficacy of chemotherapy or radiotherapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethical Committee, BLDE (Deemed to be University), Shri BM Patil Medical College, Hospital, and Research Centre issued approval IEC/NO-09/2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shaik et al.)

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]

Background: Child marriage (marital age less than 18 years) is recognized as a violation of human rights. However, it remains a deep-rooted social problem in Nepal. We aimed to find out the relationship between child marriage and reproductive health and cervical neoplasia. Methods: A cross-sectional study was conducted from March 2016 to January 2017 in the Jumla district of Karnali province, Nepal. Apparently healthy, married women ages 20–65 were invited to participate in a cervical screening awareness program followed by an interview and examination. Interviews to obtain sociodemographic and reproductive health information were followed by cervical cancer screening by cytology and visual tests. Results: Out of 2190 eligible participants, 1450 (66%) reported child marriage. Illiteracy, smoking, multiparity, number of living children, and abortion rates were all significantly higher among the women who had a marital age of less than 18. Reports of abnormal cytology, visual inspection with acetic acid, and Lugol's iodine were not significantly different among the two groups of women who married before or after the age of 18. Conclusions: Child marriage is highly prevalent in Jumla, Karnali of Nepal and is associated with poor reproductive health outcomes, but is not significantly associated with an increase in cervical neoplasia as judged by visual inspection or cytology. It is highly recommended that child marriage in Nepal be prevented by improving awareness of the risks of child marriage, education, socioeconomic status, and strict implementation of the existing marriage age law.

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]

ObjectivePlasma HIV RNA levels have been associated with the risk of human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive women. However, little is known regarding local genital tract HIV RNA levels and their relation with cervical HPV and neoplasia.Design/methodsIn an HIV-seropositive women's cohort with semiannual follow-up, we conducted a nested case-control study of genital tract HIV RNA levels and their relation with incident high-grade squamous intraepithelial lesions (HSIL) subclassified as severe (severe HSIL), as provided for under the Bethesda 2001 classification system. Specifically, 66 incidents of severe HSIL were matched to 130 controls by age, CD4 count, highly active antiretroviral therapy use, and other factors. We also studied HPV prevalence, incident detection, and persistence in a random sample of 250 subjects.ResultsRisk of severe HSIL was associated with genital tract HIV RNA levels (odds ratio comparing HIV RNA ≥ the median among women with detectable levels versus undetectable, 2.96; 95% confidence interval: 0.99 to 8.84; Ptrend = 0.03). However, this association became nonsignificant (Ptrend = 0.51) after adjustment for plasma HIV RNA levels. There was also no association between genital tract HIV RNA levels and the prevalence of any HPV or oncogenic HPV. However, the incident detection of any HPV (Ptrend = 0.02) and persistence of oncogenic HPV (Ptrend = 0.04) were associated with genital tract HIV RNA levels, after controlling plasma HIV RNA levels.ConclusionsThese prospective data suggest that genital tract HIV RNA levels are not a significant independent risk factor for cervical precancer in HIV-seropositive women, but they leave open the possibility that they may modestly influence HPV infection, an early stage of cervical tumorigenesis.

Aim:To evaluate the results of colposcopy-guided biopsy in patients diagnosed with low- and high-grade cervical intraepithelial neoplasia (CIN) identified by Pap smear test.Methods:A total of 102 patients with low- and high-grade CIN diagnosed by Pap smear test, who underwent colposcopy-guided biopsy in the gynecology and obstretrics outpatient clinics at Haseki Tranining and Research Hospital, were included in this retrospective study.Results:One hundred and two patients were included in our study. Colposcopy-guided biopsy results of patients with low-grade and high-grade CIN were as follows: acanthosis and chronic cervicitis-36 (50%) and five (16%), CIN I - 28 (38%) and nine (30%), and CIN II-III - 8 (11%) and 16 (53%), respectively. The specificity and sensitivity of colposcopy-guided biopsy in detecting CIN II-III in patients with high-grade CIN were 67% and 80%, respectively, and the positive predictive value was 50%.Conclusion:Considering the fact that smear is a screening test, the diagnosis of low-grade and high-grade CIN should be confirmed with colposcopy-guided biopsy.

Yuwadee Itarat, Chumnan Kietpeerakool, Nampet Jampathong, Bandit Chumworathayi, Pilaiwan Kleebkaow, Apiwat Aue-aungkul, Wilasinee NhokaewDepartment of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandCorrespondence: Chumnan KietpeerakoolDepartment of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, 123 Mittraphap Road, Nai-Muang, Muang District, Khon Kaen 40002, ThailandEmail kiet_ji@hotmail.comObjective: This study assessed whether sexual behavior, including engaging in early sexual intercourse and having had multiple sexual partners, can predict the risk of infection with cervical human papillomavirus (HPV) types 16 and 18.Methods: Records were reviewed of women who underwent cervical cancer screening and were found to be infected with high-risk HPV. The genotypes of high-risk HPV were categorized as HPV 16, HPV 18, and other than 16 or 18. Early sexual intercourse was defined as first sexual intercourse at the age of 19 years or younger. Multiple sexual partners was defined as having more than three lifetime sexual partners. Associations between sexual behavior and HPV 16/18 infection were presented as odds ratios (ORs) and 95% confidence intervals (CIs).Results: Of the 349 women included in the study, 72 (20.6%) and 30 (8.6%) were infected by HPV 16 and 18, respectively. Eighty-two women (26.0%) reported having engaged in early sexual intercourse, and 33 (10.4%) reported having had multiple sexual partners. After adjustment for age, parity, and smoking habits, we found that women who had engaged in early sexual intercourse tended to have a higher risk of HPV 16 (OR 1.74; 95% CI 0.93–3.29), and those who had had multiple sexual partners were found to be at a significantly higher risk for HPV 18 (OR 4.58; 95% CI 1.44–14.58).Conclusion: Sexual behavior was associated with an increased risk of HPV 16/18 infection. Engaging in early sexual intercourse increased the risk of HPV 16 infection, and having had multiple sexual partners increased that of HPV 18.Keywords: sexual behavior, human papillomavirus, cervical neoplasia, sexual partner

Abstract 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.

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]

Cervical Cancer (CC) is a significantly prevalent disease in developing countries. Currently, targeted therapies are not a primary standard of care in CC. This information could be crucial for developing directed therapies and patient screening for biomarkers that would allow personalised treatment of CC. This systematic review aimed to estimate the prevalence of potential therapeutic targets such as the epidermal growth factor receptor (EGFR) and the PI3K/Akt/mTOR and Ras/Raf/MAPK pathways in patients with CC, identified through genomic and non-genomic testing. Studies were identified through an ad-hoc search strategy from the available on MEDLINE (Ovid), CENTRAL, LILACS, SCOPUS, through the Clinical Trial registry on Clinicaltrials.gov, International Clinical Trials Registry Platform, RENIS (Argentine National Registry of Health Research) and grey literature sources. We included 74 studies which represented a total pool of 7,862 participants. Forty-five studies informed mutations of EGFR, with a combined positivity rate of 53% (95%CI: 45%-60%; I² = 95%). Twenty studies informed the presence of mutations in PIK3CA with a combined positivity rate of 30% (95%CI: 21%-39%; I² = 96%). Twenty-three studies reported a mutation in Ras, with a combined positivity rate of 14% (95%CI: 8%-21%; I² = 95%). Raf mutations were informed in six studies. Six studies informed the presence of Akt mutations, two studies informed mTOR mutations and only one study reported mutations of MAPK. The most frequently described therapeutic targets were EGFR, and the PIK3CA and Ras pathways, though inconsistency in positivity rates was significant. Our study did not allow the identification of any specific clinical characteristics that might explain the observed heterogeneity. Despite the overall good quality of the included studies, the applicability of these results to patients' general population with CC is still unclear. [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 Background Several epidemiological researches have indicated that microvessel density (MVD), reflecting angiogenesis, was a negatively prognostic factor of cervical cancer. However, the results were inconsistent. Therefore, we performed a meta-analysis to evaluate the association between microvessel density and the survival probability of patients with cervical cancer. Method There was a comprehensive search of the PubMed, EMBASE and Cochrane databases up to August 31, 2017. Based on a fixed-effects or random-effects model, the hazard ratio (HR) and 95% confidence intervals (CIs) were calculated from researches on overall survival (OS) and disease-free survival (DFS). Result Totally, we included 13 observational researches, involving 1097 patients with cervical cancer. The results showed that high level of microvessel density was negatively correlated with OS (HR = 1.79, 95% CIs 1.31–2.44, I 2 = 60.7%, P = 0.003) and DFS (HR = 1.47, 95% CIs 1.13–1.80, I 2 = 0%, P = 0.423) of cervical cancer patients. In subgroup analysis, high counts of MVD were significantly associated with a poor survival (including OS and DFS) of the patients detected by anti-factor VIII antibodies or in European origin. Conclusion The present meta-analysis indicated that survival with high level of MVD was significant poorer than with low MVD in cervical cancer patient. Standardization of MVD assessment is needed.

Manuela Viviano,1 Alexia Willame,1 Marie Cohen,1 Anne-Caroline Benski,1 Rosa Catarino,1 Christine Wuillemin,1 Phuong Lien Tran,1 Patrick Petignat,1 Pierre Vassilakos2 1Division of Gynecology, Geneva University Hospitals, Geneva, Switzerland; 2Geneva Foundation for Medical Education and Research, Geneva, Switzerland 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

Abstract Objective The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association. Methods Women with IB stage-ICSCC (n = 20) and women with uterine leiomyoma (n = 20) were prospectively evaluated. Patients with ICSCC were submitted to type BC1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies. Results The WWOX expression was significantly lower in the tumor compared with the expression in thebenign cervix (p = 0.019). TheWWOXexpressionwas inversely associated with the CD31 expression in the tumor samples (p = 0.018). There was no association betweentheWWOXexpression with the p53 expression (p = 0.464)or the Ki-67expression (p = 0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size (p = 0.156), grade of differentiation (p = 0.914), presence of lymphatic vascular invasion (p = 0.155), parametrium involvement (p = 0.421) or pelvic lymph node metastasis (p = 0.310) in ICSCC tissue samples. Conclusion The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.

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]

Cervical cancer screening is an essential component of prenatal care. The diagnosis and management of cervical intraepithelial neoplasia (CIN) during pregnancy are challenging, and sufficient information does not exist to allow for a definitive evidence-based approach. The American Society for Colposcopy and Cervical Pathology has recently published guidelines regarding the evaluation of abnormal Papanicolaou tests and the treatment of CIN in this setting. Many techniques traditionally recommended in the evaluation of abnormal cervical cytology and the treatment of CIN in the nonpregnant woman, such as colposcopy, cervical biopsy, and electrosurgical excision, can be applied to the pregnant patient with important exceptions. The vascular cervix associated with the gravid condition and the risk of premature pregnancy loss mandates deviation from existing consensus guidelines in screening for cervical cancer in pregnancy and treating associated CIN. In the present review, current guidelines regarding cervical cancer screening are reviewed, and data from studies of pregnant populations are summarized.