High-grade Cervical Lesions Research Articles

ADCY7 mRNA Is a Novel Biomarker in HPV Infection and Cervical High-Grade Squamous Lesions or Higher

The effect of cervical cancer immunotherapy is limited. Combination therapy will be a new direction for cervical cancer. Thus, it is essential to discover a novel and available predictive biomarker to stratify patients who may benefit from immunotherapy for cervical cancer. In this study, 563 participants were enrolled. Adenylate cyclase 7 (ADCY7) mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between ADCY7 and cervical intraepithelial neoplasia in grade 2 and higher (CIN2+) was analyzed, and the optimal cut-off values of the relative expression of ADCY7 mRNA to predict CIN2+ were calculated. In addition, the clinical significance of ADCY7 in cervical cancer was determined by the Kaplan-Meier Cox regression based on the TCGA database. The mean ADCY7 mRNA expression increased significantly with cervical lesion development, especially compared with CIN2+ (p < 0.05). Moreover, the expression of ADCY7 increased significantly in high-risk human papillomavirus (HR-HPV) infection but not in HPV-A5/6 species. The area under the receiver operating characteristic curve (AUC) of ADCY7 was 0.897, and an optimal cut-off was 0.435. Furthermore, ADCY7 had the highest OR (OR= 8.589; 95% CI (2.281-22.339)) for detecting CIN 2+, followed by HPV genotyping, TCT, and age (OR = 4.487, OR = 2.071, and OR = 1.345; 95% CI (1.156-10.518), (0.370-8.137), and (0.171-4.694), respectively). Moreover, this study indicated that higher ADCY7 levels could be a suitable predictor for poor prognosis in cervical cancer due to immune cell infiltration. A new auxiliary predictor of CIN2+ in cervical cytology specimens is ADCY7 ≥ 0.435. Furthermore, it may be a promising prognosis predictor and potential immunotherapy target for the combined treatment of cervical cancer and possibly further block HR-HPV persistent infection.

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

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

HPV genotypes in high-grade cervical lesions and invasive cervical carcinoma detected in Gabonese women

BackgroundCervical cancer is the third most common cancer among women worldwide, but particularly affects women living in sub-Saharan Africa. Screening and vaccination programs are two prevention approaches that can reduce cervical cancer incidence. However, effective vaccination campaigns require better knowledge of the prevalence of the main human papillomavirus (HPV) genotypes reported in high-grade neoplastic lesions and invasive carcinomas in women.MethodsAll samples collected in this study were processed using standard histopathological methods with haematoxylin and eosin staining of the sections. Areas with abnormal cells were then identified. The HPV genotype was determined on the DNA extracted from the same sections using nested PCR followed by amplicon sequencing and real-time PCR specific to five different HPV genotypes (16, 18, 33, 45 and 58).ResultsA total of 132 Gabonese patients with high-grade neoplastic lesions were included in this study; 81% were squamous cell carcinomas (SCC). At least one HPV was detected in 92.4% patients; HPV16 (75.4%) was the most frequent genotype, followed by HPV18, 58, 45, 33 and 35. Moreover, histological analysis showed that SCC samples had 50% and 58.2% stage III and IV tumor cells, respectively, according to the FIGO classification. Finally, 36.9% of these stage III and IV patients were less than 50 years old.ConclusionsOur results confirm the high prevalence of HPV16 and 18 genotypes among high-grade lesions in Gabonese women. This study confirms the need for a national strategy for early screening of precancerous lesions associated with a broad national vaccination program among non-sexually active women to significantly reduce the long-term cancer burden.

PSGL-1 is a novel tumor microenvironment prognostic biomarker with cervical high-grade squamous lesions and more.

Macrophages secrete many cytokines and chemokines, which can provoke either an anti-tumor or pro-tumor immune response. P-selectin glycoprotein ligand-1 (PSGL-1) is expressed in macrophages and plays a vital role in synergizing for a more robust anti-tumor response. However, there are few studies about PSGL-1 expression status and clinical value of biological function in cervical cancer. In this study, 565 participants were enrolled. PSGL-1 mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between PSGL-1 and cervical intraepithelial neoplasia in two grades and more (CIN2+) was analyzed, and the optimal cut-off values of PSGL-1 to predict CIN2+ were calculated. In addition, the clinical significance of PSGL-1 in cervical cancer was determined by Kaplan-Meier Cox regression based on the database. The mean PSGL-1 increased significantly with cervical lesion development, especially compared with CIN2+ (p<0.05). Moreover, the expression of PSGL-1 increased significantly in HPV-16/18 positive and HPV-18 positive, but not in HPV-16 positive and other HR-HPV positive. And then, it demonstrated that the area under the receiver operating characteristic curve (AUC) of PSGL-1 was 0.820, and an optimal cut-off 0.245. Furthermore, the PSGL-1 had the highest odds ratio and highest OR (OR= 8.707; 95% CI (.371-19.321)) for the detection of CIN 2+. In addition, our result also indicated that higher PSGL-1 expression was significantly related to a better prognosis in cervical cancer due to immune cell infiltration. PSGL-1≥0.245 in cervical cytology specimens is a new auxiliary biomarker of CIN2+, and it may be a promising prognosis predictor and potential immunotherapy target linked with immune infiltration of cervical cancer.

Anal Cancer in Systemic Lupus Erythematosus Patients is a Neglected Condition

AbstractPatients with systemic lupus erythematosus have a higher incidence of neoplasms associated with human papillomavirus infections, such as those that affect the vulva, the vagina, and the cervix; however, little is known about the frequency of anal cancer among these patients. Although there are recommendations for screening for this cancer in immunosuppressed individuals, it is possible that this procedure is not strictly followed. We describe the case of a 47-year-old woman with systemic lupus erythematosus who was treated with immunosuppressants and developed advanced anal squamous cell carcinoma after adequate treatment and healing of a high-grade cervical squamous intraepithelial lesion. Five years after the completion of the anal cancer treatment, the patient presented with cystic hepatic lesions that were histopathologically confirmed to be metastatic squamous cell carcinoma. This report aimed to highlight the need for anal cancer screening in patients with lupus, particularly if there was a history of cervical cytopathological alterations.

P16INK4A flow cytometry of exfoliated cervical cells: Its role in quantitative pathology and clinical diagnosis of squamous intraepithelial lesions.

P16INK4A is a surrogate signature compensating for the specificity and/or sensitivity deficiencies of the human papillomavirus (HPV) DNA and Papanicolaou smear (Pap) co-test for detecting high-grade cervical squamous intraepithelial lesions or worse (HSIL+). However, traditional p16INK4A immunostaining is labour intensive and skill demanding, and subjective biases cannot be avoided. Herein, we created a high-throughput, quantitative diagnostic device, p16INK4A flow cytometry (FCM) and assessed its performances in cervical cancer screening and prevention. P16INK4A FCM was built upon a novel antibody clone and a series of positive and negative (p16INK4A -knockout) standards. Since 2018, 24100-women (HPV-positive/-negative, Pap-normal/-abnormal) have been enrolled nationwide for two-tier validation work. In cross-sectional studies, age- and viral genotype-dependent expression of p16INK4A was investigated, and optimal diagnostic parameter cut-offs (using colposcopy and biopsy as a gold standard) were obtained. In cohort studies, the 2-year prognostic values of p16INK4A were investigated with other risk factors by multivariate regression analyses in three cervicopathological conditions: HPV-positive Pap-normal, Pap-abnormal biopsy-negative and biopsy-confirmed LSIL. P16INK4A FCM detected a minimal ratio of 0.01% positive cells. The p16INK4A -positive ratio was 13.9±1.8% among HPV-negative NILM women and peaked at the ages of 40-49 years; after HPV infection, the ratio increased to 15.1±1.6%, varying with the carcinogenesis of the viral genotype. Further increments were found in women with neoplastic lesions (HPV-negative: 17.7±5.0-21.4±7.2%; HPV-positive: 18.0±5.2-20.0±9.9%). Extremely low expression of p16INK4A was observed in women with HSILs. As the HPV-combined double-cut-off-ratio criterion was adopted, a Youden's index of 0.78 was obtained, which was significantly higher than that (0.72) of the HPV and Pap co-test. The p16INK4A -abnormal situation was an independent HSIL+ risk factor for 2-year outcomes in all three cervicopathological conditions investigated (hazard ratios: 4.3-7.2). FCM-based p16INK4A quantification offers a better choice for conveniently and precisely monitoring the occurrence of HSIL+ and directing risk-stratification-based interventions.

Prediction of cervical cancer precursor lesions by quantitative methylation specific PCR: A retrospective study.

This study was undertaken to evaluate the performance of FAM19A4 and hsa-mir-124-2 hypermethylation as a triage tool for women who are at risk of developing cervical cancer or high-grade cervical cancer precursor lesions by taking into consideration the cytology report, histology diagnosis, and human papillomavirus (HPV) status. A total of 330 cervical ThinPrep samples were retrospectively collected and used for DNA isolation. HPV DNA was detected by real-time polymerase chain reaction (PCR), and HPV genotypes were identified by Sanger-based sequencing. DNA extracts were bisulphite-treated, and hypermethylation of FAM19A4 and hsa-mir-124-2 genes was detected by a quantitative methylation-specific PCR (qMSP) test using the QIAsure Methylation assay. Hypermethylated genes were detected in 27 (9.6%) cervical samples, mostly found in women diagnosed with high-grade squamous intraepithelial legions (77.8%) or cervical intraepithelial neoplasia grade 3 (CIN3) (72.7%). The sensitivity and the specificity of the qMSP test for predicting CIN3 lesions among women with high-risk HPV was 75% and 91%, respectively. There was a significant correlation between high-grade cervical cancer precursor lesions and detection of hypermethylated genes in samples positive for high-risk HPV. Our results suggest that the QIAsure Methylation test can be used as a triage tool to identify women at risk for cervical cancer progression.

Performance of standardised colposcopy to detect cervical precancer and cancer for triage of women testing positive for human papillomavirus: results from the ESTAMPA multicentric screening study

Colposcopy, currently included in WHO recommendations as an option to triage human papillomavirus (HPV)-positive women, remains as the reference standard to guide both biopsy for confirmation of cervical precancer and cancer and treatment approaches. We aim to evaluate the performance of colposcopy to detect cervical precancer and cancer for triage in HPV-positive women. This cross-sectional, multicentric screening study was conducted at 12 centres (including primary and secondary care centres, hospitals, laboratories, and universities) in Latin America (Argentina, Bolivia, Colombia, Costa Rica, Honduras, Mexico, Paraguay, Peru, and Uruguay). Eligible women were aged 30-64 years, sexually active, did not have a history of cervical cancer or treatment for cervical precancer or a hysterectomy, and were not planning to move outside of the study area. Women were screened with HPV DNA testing and cytology. HPV-positive women were referred to colposcopy using a standardised protocol, including biopsy collection of observed lesions, endocervical sampling for transformation zone (TZ) type 3, and treatment as needed. Women with initial normal colposcopy or no high-grade cervical lesions on histology (less than cervical intraepithelial neoplasia [CIN] grade 2) were recalled after 18 months for another HPV test to complete disease ascertainment; HPV-positive women were referred for a second colposcopy with biopsy and treatment as needed. Diagnostic accuracy of colposcopy was assessed by considering a positive test result when the colposcopic impression at the initial colposcopy was positive minor, positive major, or suspected cancer, and was considered negative otherwise. The main study outcome was histologically confirmed CIN3+ (defined as grade 3 or worse) detected at the initial visit or 18-month visit. Between Dec 12, 2012, and Dec 3, 2021, 42 502 women were recruited, and 5985 (14·1%) tested positive for HPV. 4499 participants with complete disease ascertainment and follow-up were included in the analysis, with a median age of 40·6 years (IQR 34·7-49·9). CIN3+ was detected in 669 (14·9%) of 4499 women at the initial visit or 18-month visit (3530 [78·5%] negative or CIN1, 300 [6·7%] CIN2, 616 [13·7%] CIN3, and 53 [1·2%] cancers). Sensitivity was 91·2% (95% CI 88·9-93·2) for CIN3+, whereas specificity was 50·1% (48·5-51·8) for less than CIN2 and 47·1% (45·5-48·7) for less than CIN3. Sensitivity for CIN3+ significantly decreased in older women (93·5% [95% CI 91·3-95·3] in those aged 30-49 years vs 77·6% [68·6-85·0] in those aged 50-65 years; p<0·0001), whereas specificity for less than CIN2 significantly increased (45·7% [43·8-47·6] vs 61·8% [58·7-64·8]; p<0·0001). Sensitivity for CIN3+ was also significantly lower in women with negative cytology than in those with abnormal cytology (p<0·0001). Colposcopy is accurate for CIN3+ detection in HPV-positive women. These results reflect ESTAMPA efforts in an 18-month follow-up strategy to maximise disease detection with an internationally validated clinical management protocol and regular training, including quality improvement practices. We showed that colposcopy can be optimised with proper standardisation to be used as triage in HPV-positive women. WHO; Pan American Health Organization; Union for International Cancer Control; National Cancer Institute (NCI); NCI Center for Global Health; National Agency for the Promotion of Research, Technological Development, and Innovation; NCI of Argentina and Colombia; Caja Costarricense de Seguro Social; National Council for Science and Technology of Paraguay; International Agency for Research on Cancer; and all local collaborative institutions.

Complications of Loop Electrosurgical Excision Procedure Following Treatment of Cervical Intra-Epithelial Neoplasia 2 &amp; 3

Background: The loop electrosurgical excision procedure (LEEP) is currently one of the most commonly used approaches to treat high grade cervical squamus intraepithelial lesion confirmed on colposcopic guided biopsy examination. Complications of electrosurgical excision procedure (LEEP) are rare. But in Bangladesh, we have very limited research-based information regarding this issue. Aim of the Study: The aim of the study was to assess the complications of loop electrosurgical excision procedure following treatment of cervical intra-epithelial neoplasia (CIN) 2 and 3. Methods: This descriptive cross-sectional study was conducted in OPD, Gynaecology and Obstetrics Department, Rangpur Medical College Hospital, Rangpur, Bangladesh during the period of July 2011 to June 2012. In total, 75 patients with CIN 2 and/or 3 were enrolled in this study as study subjects. The study was approved by the ethical committee of the mentioned hospital. Proper informed written consents were taken from all the participants before data collection. The criteria for inclusion were colposcopic guided biopsy revealing CIN 2 or 3 whose lesion remains confined to ectocervix. The least amount of power that will effectively perform the electrosurgery should be used, so as to minimize the risk to the patient’s normal tissues and ensure that the excised specimen is inacceptable condition for pathological assessment. Data analysis was done by using statistical package for social science (SPSS) 16 versions. Results: In analyzing the post procedure complications of the participants, we observed that, 64% participants were from vaginal discharge. Besides this 21%, 9%, 4% and 1% cases were found with pain, bleeding, fever and cervical stenosis consequently. Distributing persistence of vaginal discharge, 44% participants taken 5-10 days which was noticeable. Only 5.33% participants had vaginal discharge in between 21-25 days. In distributing persistence of pain, we observed that, 8% participants had taken 30 days to be cured which was the highest number of patients. Within one week, all the patients become free from fever. Cervical Stenosis occurred as a delayed complication during follow up at 9-12 months after LEEP in only 1(1.3%) case and occurred at 270th day. Conclusion: As per the findings of this study we can mention vaginal discharge as the most common complication for the cervical intra-epithelial neoplasia patients by treating loop electrosurgical excision procedure. Besides these, physicians should be aware about the sufferings of patients from pain and bleeding. Finally, we can conclude that, LEEP as an easy safe and acceptable treatment for high grade CIN with high cure rate.

High-risk human papillomavirus genotype distribution among women with gynecology complaints in northwest Ethiopia

BackgroundHuman papillomavirus (HPV) genotypes differ by geographic location. With the advent of HPV vaccination and HPV-based cervical screening tests in Ethiopia, a nationwide dataset on the genotype distribution of HPV among women has paramount importance in the fight against cervical cancer. However, there is limited data in this regard in the northwest part of the country. Therefore, this study aimed to identify the genotype distribution of high-risk HPVs among women presenting with cervical abnormalities.MethodsA health facility-based cross-sectional study was conducted at Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Bahir Dar–Ethiopia. Women aged ≥ 30 years who visited the hospital gynecology unit from 01 March 2019 to 30 October 2021 were included. Following general and pelvic examinations, a senior gynecologist collected cervical punch biopsies for histopathological examinations and cervical swabs for HR-HPV detection using the Abbott Alinity m system (Abbott Molecular, Des Plaines, IL, USA). Extended genotyping was carried out with the INNO-LiPA HPV Genotyping Extra II assay (INNO-LiPA; Fujirebio Europe, Ghent, Belgium) as per the manufacturer protocols at the Institute of Virology, Leipzig University Hospital, Germany.ResultsWe included 355 women with a mean age of 46.4 ± 11.4 years. The majority of the participants, 277 (79.4%) were sexually active before the age of 18 years and 180 (51.6%) had multiple sexual partners. Forty-eight (13.5%) of the participants were HIV positive. The proportion of HR-HPV was 53.0% (n = 188; 95%CI: 47.8–58.1%). From these samples, 13 different HR-HPV types with a total of 258 sequences were identified. The detection of HR-HPV increased significantly with an increase in the age of the participants. The predominant identified HR-HPV was HPV16, 50.4% followed by HPV31 (9.7%), HPV33 (8.5%), HPV39, and HPV68 each (5.8%) and HPV18 (4.7%). Of the total HR-HPV-positive women, 23.9% (45/188) were infected with multiple HR-HPV types. All HPV16, HPV18, HPV35, and HPV45 genotypes (as a single or in coinfections) were found to be associated with either high-grade lesions or cervical cancer.ConclusionsHR-HPV infection was reportedly higher among women in the present study area. Based on our findings, we strongly recommend the nonavalent HPV vaccine for immunization and any HPV-based screening method to take into consideration the predominant genotypes circulating in the country. The role of multiple HPV infections in high-grade cervical lesions entails further study in Ethiopia.

Evaluation of Human Papilloma Virus (HPV) Genotyping and Viral Load Determination as Diagnostic Biomarkers of Cervical Cancer Risk.

HPV testing in cervical cancer screening programs offers the possibility of introducing molecular standardized biomarkers for the triage of HPV-positive women. This study aimed to evaluate the role of HPV genotyping and viral load as possible diagnostic biomarkers of high-grade cervical lesions (CIN2+) by performing a preliminary evaluation of a new HPV test. Cervical specimens were obtained from 200 women referred for a colposcopy. Samples were tested using both Anyplex™ II HR-HPV as well as OncoPredict HPV® Screening (SCR) and quantitative typing (QT). Using a cycle threshold cutoff (Ct) of 36.8 for the SCR assay and 1.27 log10 (viral copies/104 cells) for the QT assay, relative clinical sensitivity for CIN2+ and relative clinical specificity for CIN2- as compared to Anyplex™ II HR-HPV were, respectively, 0.92 and 1.00 for SCR and 1.35 and 1.24 for QT. The distribution of high-risk HPV (HR-HPV) genotypes (p = 0.009) as well as the viral copy numbers (CIN2-: 3.7 log10 (viral copies/104 human cells); CIN2+: 4.3 log10 (viral copies/104 human cells); p = 0.047) were found to differ in women with high- and low-grade cervical lesions, suggesting a possible role of HPV genotyping and normalized viral load as potential biomarkers to identify women at increased risk of cervical lesions.

Comparison of HPV 16/18 Genotyping and p16/Ki67 Dual Staining for Detection of High-Grade Cervical Lesion in Patients with Low-Grade Cervical Smears.

To triage low-grade cervical smears (ASCUS/LSIL) by HPV 16/18 genotyping and dual staining with p16/Ki67 and to compare the sensitivity and specificity of these two triage methods for detection of high-grade cervical intraepithelial neoplasia (HGCIN). In this prospective cross-sectional study, we evaluated a total of 89 women with low-grade smears (54 ASCUS, 35 LSIL) recruited from a tertiary care hospital. All patients underwent colposcopy guided cervical biopsy. Histopathology was used as gold standard. All samples were subjected to HPV 16/18 genotyping (excluding 9) using DNA PCR and p16/Ki67 dual staining (excluding 4) using Roche® kit. We then compared the two triage methods to detect high-grade cervical lesions. Overall, in all low-grade smears sensitivity, specificity and accuracy of HPV 16/18 genotyping, was found to be 66.7%, 77.1% and 76.2% respectively (p = 0.03). In low-grade smears sensitivity, specificity and accuracy of dual staining, was found to be 66.7%, 84.8% and 83.5% respectively (p = 0.01). Overall, in all low-grade smears the sensitivity of the two tests was comparable. However, dual staining had a higher specificity and accuracy than HPV 16/18 genotyping. It was concluded that both are effective triage methods but dual staining had a better performance than HPV 16/18 genotyping.

LEEP excision of high grade cervical intraepithelial lesion to achieve appropriate excision margins

LEEP excision of high grade cervical intraepithelial lesion to achieve appropriate excision margins

Risk Factors for Persistence or Recurrence of High-Grade Cervical Squamous Intraepithelial Lesions.

to evaluate whether the colposcopic lesion size , age, kind of surgery, the status of the surgical margins and the expression of the p16 and Ki-67 immunomarkers are risk factors for persistence or recurrence of the lesion. a cross-sectional, observational, retrospective study of patients submitted to cold knife conization (CKC) or the loop electrosurgical excision procedure for cervical intraepithelial neoplasia 2 or 3. The colposcopic lesion size, age, surgical method, involvement of the surgical margins, and p16/Ki-67 immunomarker expression were analyzed in relation to lesion persistence and recurrence. seventy-one women were treated with cold knife conization and 200 were treated with loop electrosurgical excision. Of these, 95 had cervical intraepithelial neoplasia 2, 173 had cervical intraepithelial neoplasia 3, 183 had free surgical margins, 76 had compromised margins, and 12 showed damage by processing artifact or fragments. Among the 76 cases with positive margins, 55, 11, and 10 showed endocervical margin involvement, ectocervical margin involvement, and both endocervial and ectocervical margin involvement, respectively. Of the 264 followed-up patients, 38 had persistent or recurrent disease. A multiple logistic regression indicated that positive endocervical margins are the only independent risk factor for the persistence/recurrence of cervical intraepithelial neoplasia. No significant association was identified between the colposcopic lesion size, age, surgery type, or p16/Ki-67 immunomarker expression and lesion persistence or recurrence.

Risk Factors for Persistence or Recurrence of High-Grade Cervical Squamous Intraepithelial Lesions

RESUMO Objetivos: avaliar se o status das margens, idade, tamanho da lesão colposcópica, tipo de cirurgia e expressão dos marcadores p16/Ki-67 são fatores de risco na persistência ou recidiva da LIEAG. Métodos: um estudo de corte transversal, observacional com coleta de dados retrospectivos de pacientes submetidas a conização a frio (CF) ou exérese da zona de transformação por cirurgia de alta frequência EZT por NIC2/3. Foram analisados os seguintes fatores em relação a persistência ou recidiva: comprometimento das margens, idade, tamanho da lesão, tipo de cirurgia e coexpressão dos imunomarcadores p16 e Ki-67. Resultados: 271 mulheres tratadas com CF (71) e EZT (200), onde 95 apresentavam NIC 2 e 173 NIC 3, 183 apresentaram margens cirúrgicas livres, 76 comprometidas e 12 prejudicadas por artefatos ou fragmentação. Das 76 pacientes com margens comprometidas, 55 foram endocervical, 11 ectocervical e 10 ambas as margens. Das 264 pacientes que tiveram seguimento, 38 persistiram ou recidivaram a doença. A regressão logística múltipla indicou ser a margem endocervical comprometida o único fator independente de risco de persistência/recorrência da NIC (p&lt;0,001). Não houve associação significativa entre a idade, o tamanho da lesão colposcópica, o tipo de cirurgia e a expressão dos imunomarcadores p16/Ki-67 e a persistência ou recorrência da doença. Conclusão: entre os fatores estudados associados com persistência ou recorrência, somente a margem endocervical comprometida provou ser significativamente um fator risco para persistência ou recorrência da lesão.

Is cervical dysplasia a major concern in females with inflammatory bowel disease? A Spanish retrospective study.

Cervical cancer (CC) is the fourth most common cancer affecting women worldwide. The risk of women immunosuppressed due to AIDS or organ transplantation is well documented, as most cases are caused by persistent human papillomavirus (HPV) infection and immunosuppression can prevent clearing HPV. Although European guidelines advise that inflammatory bowel disease (IBD) women under immunosuppression should be screened for CC as regularly as high-risk patients, quality evidence is lacking in our country. We performed a retrospective case-control (2020-2021) study to analyse the risk factors associated with the appearance of low-grade (LSIL) or high-grade (HSIL) squamous intraepithelial cervical lesions in patients with IBD. We included all women aged 21-65 years , followed up at the University Hospital Fundación Alcorcón (Spain). Cases were defined as those patients with abnormalities in cervical cytology, while the control group consisted of the rest of the women. Disease characteristics, treatments and epidemiological data (smoking habit, sexual behaviour and reproductive history) were obtained. We documented the evolution of abnormalities over time and compare data between women under immunosuppressive treatment or not.

The Immunomodulation Role of Vaginal Microenvironment On Human Papillomavirus Infection.

Evidence suggests the role of the vaginal microbiome and microenvironment in the immunity state. The human papillomavirus (HPV) infection is widely dependent on the healthy vaginal microenvironment. Hence, this study aimed to investigate the role of the vaginal microenvironment in the rate of high-risk HPV (hr-HPV) infection. This cross-sectional study was performed on 512 women with hr-HPV positive (n=212) or negative (n=300) infection. The vaginal samples of women were examined regarding yeas and Gardnerella vaginalis infection. Also, Lactobacillus acidophilus, pH, and enzyme activity (such as catalase, proline aminopeptidase, and leucocyte esterase) were compared between the two groups. Also, the histopathological study was performed on the vaginal samples. The higher rate of yeast and G. vaginalis infections as well as decreased L. acidophilus, were significantly observed in women with hr-HPV positive infection (P0.001). Also, histopathological findings indicated that cervical intraepithelial neoplasia grade I-III and cervical cancer lesions were markedly higher in hr-HPV positive group compared with control women. The hr-HPV infection was markedly correlated to vaginal microenvironments, and it could a risk factor for the elevation of the rate of high-grade cervical lesions.

Histologıcal results of HPV genotyping from a colposcopy center.

To investigate the role of partial human papillomavirus (HPV) genotyping tests in predicting the diagnosis of high-grade cervical intraepithelial lesion and cancer (HSIL +) as a result of colposcopic histopathology. The study included 2872 patients who presented at our colposcopy unit between January 1, 2015 and December 31, 2019 and underwent colposcopy for the first time. The patients were compared in terms of HSIL + results as HPV 16/18 and HPV other type positive groups. HSIL + was determined at the rate of 22.3% in the HPV 16/18 group and at 7.0% in the HPV Other group, and the difference was statistically significant (p = 0.000). HPV 16/18 types were found to be responsible for 84.8% of cervical cancers and 83.5% of HSIL and worse cases. Partial HPV 16/18 genotyping is an effective strategy in the triage of HPV-positive women. HPV type identification consistent with the epidemiology of HPV types in HSIL + cases in the screened population, and the age-appropriate use of primary HPV tests will determine the sensitivity and cost effectiveness of screening.

The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion.

Human papillomavirus (HPV) is the major pathogen for cervical lesions. The evasion mechanism of the immune response and persistence of HPV infection can be influenced by polymorphisms (SNPs) in genes associated with transporter associated with antigen processing (TAP), which may change the peptide binding affinity or the TAP expression impacting the efficiency of peptide transport in the secretory pathway, and the presentation of peptides to cytotoxic T lymphocytes. This study aimed to evaluate the role of the TAP1 and TAP2 polymorphisms, TAP1, and TAP2 genes expressions, and protein levels in cervical cells presenting different degrees of pre-cancerous lesions in 296 immunocompetent women infected or not by HPV. TAP SNPs were genotyped by Sanger sequencing, and gene expression by real-time PCR. Aneuploidy was determined by DNA index using flow cytometry. TAP-1 and TAP-2 tissue expressions were evaluated by immunohistochemistry. The Asp697Gly SNP of TAP1 presented a risk for cellular aneuploidy (P=0.0244). HPV+ women had higher TAP-2 mRNA (P=0.0212) and protein (P<0.0001) levels. The TAP2D and TAP2E haplotypes were associated with the risk for aneuploidy and pre-cancerous lesions. In conclusion, nucleotide variability at the peptide binding region of peptide transporter genes, particularly of the TAP2 gene, may influence the HPV-peptide transportation from the cytosol to the endoplasmic reticulum, increasing the susceptibility to the development of high-grade cervical lesions.

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

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