Intraepithelial Cancer Research Articles

Micronutrients and prevention of cervical pre-cancer in HPV vaccinated women: a cross-sectional study.

Prophylactic vaccines against high-risk human papillomaviruses (HR-HPVs) hold promise to prevent the development of higher grade cervical intraepithelial neoplasia (CIN 2+) and cervical cancer (CC) that develop due to HR-HPV genotypes that are included, in HPV vaccines, but women will continue to develop CIN 2+ and CC due to HR-HPV genotypes that are not included in the quadrivalent HPV vaccine (qHPV) and 9-valent HPV vaccine (9VHPV). Thus, the current vaccines are likely to decrease but not entirely prevent the development of CIN 2+ or CC. The purpose of the study was to determine the prevalence and determinants of CIN 2+ that develop due to HR-HPVs not included in vaccines. Study population consisted of 1476 women tested for 37 HPVs and known to be negative for qHPVs (6/11/16/18, group A, n = 811) or 9VHPVs (6/11/16/18/31/33/45/52/58, group B, n = 331), but positive for other HR-HPVs. Regression models were used to determine the association between plasma concentrations of micronutrients, socio-demographic, lifestyle factors and risk of CIN 2+ due to HR-HPVs that are not included in vaccines. The prevalence of infections with HPV 31, 33, 35 and 58 that contributed to CIN 2+ differed by race. In group A, African American (AA) women and current smokers were more likely to have CIN 2 (OR = 1.76, P = 0.032 and 1.79, P = 0.016, respectively) while in both groups of A and B, those with higher vitamin B12 were less likely to have similar lesions (OR = 0.62, P = 0.036 and 0.45, P = 0.035, respectively). We identified vitamin B12 status and smoking as independent modifiable factors and ethnicity as a factor that needs attention to reduce the risk of developing CIN 2+ in the post vaccination era. Continuation of tailored screening programs combined with non-vaccine-based approaches are needed to manage the residual risk of developing HPV-related CIN 2+ and CC in vaccinated women.

Endoscopic submucosal dissection of anorectal Condyloma acuminatum.

Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papilloma virus infection. Although it is generally seen in the genital and perianal regions, anal canal and rectum sometimes could be involved. It has been reported to be associated with higher risk of intraepithelial neoplasia and cancer. Surgery excision and fulguration are the primary treatment, while high local recurrence rate of CA remains bothering. We presented a case of CA that detected via colonoscopy and successfully treated with endoscopic submucosal dissection.

Association of Serum Concentrations of Testosterone and Insulin with the Degree of Cervical Squamous Intraepithelial Lesions in Cuban Women

Cervical squamous intraepithelial lesions (SIL) and cervical cancer (CxCa) develop because of high-risk human papillomavirus (HR-HPV) infection; however, other cofactors such as endogenous hormones could contribute to the development of this neoplasia.

Positive Margins for High-Grade Intraepithelial Lesion after Cervical Conization - A Five-Year Retrospective Study

Overview and aim: Women treated for high-grade squamous intraepithelial lesions (HSIL) may be at increased risk for recurrent intraepithelial lesions and cervical cancer for up to 25 years.

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.

Septin9 DNA methylation as a promising biomarker for cervical cancer

Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer. Impact statement What is already known on this subject? The occurrence of cervical cancer is related to Septin9 methylation. In fresh specimens and cervical scrapings, we found the degrees of methylated Septin9 increased with growing severity of cervical lesions. Compared with HPV16/18 genotyping and cytological detection, Septin9 methylation had a better specificity and AUC in detecting ≥ HSIL. Furthermore, plasma-based Septin9 methylation also had a high specificity for pelvic lymphatic metastasis prediction. What the results of this study add? Methylation analysis of Septin9 indicated a similar sensitivity, specificity and AUC in detecting ≥ HSIL, relative to HPV16/18 genotyping. Compared with cytological method, Septin9 methylation also yielded a higher specificity and AUC in detecting ≥ HSIL. And we also found plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with SCCAg. What the implications are of these findings for clinical practice and/or further research? This study aimed to evaluate the relationship between Septin9 methylation and cervical cancer, and to explore the value of methylated Septin9 in the detection of cervical (pre)cancerous lesions. Moreover, we would explore plasma-based ctDNA biomarkers for pelvic lymphatic metastasis prediction of cervical cancer, to improve non-invasive predictive accuracy of pelvic nodal metastasis and reduce the complications caused by pelvic lymphadenectomy.

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

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

A novel multi-epitope vaccine of HPV16 E5E6E7 oncoprotein delivered by HBc VLPs induced efficient prophylactic and therapeutic antitumor immunity in tumor mice model

Human papilloma virus type 16 (HPV16) is the most prevalent etiologic agent associated with cervical cancer, and its early proteins E5, E6 and E7 play important roles in cervical epithelium transformation to cervical intraepithelial neoplasia and even cervical cancer. Hence, these oncoproteins are ideal target antigens for developing immunotherapeutic vaccines against HPV-associated infection and cervical cancer. Currently, multi-epitope vaccines have been a promising strategy for immunotherapy for viral infection or cancers. In this study, the E5aa28-46, E6aa37-57 and E7aa26-57 peptides were selected and linked to form a novel multi-epitopes vaccine (E765m), which was inserted into the major immune dominant region (MIR) of hepatitis B virus core antigen (HBc) to construct a HBc-E765m chimeric virus-like particles (cVLPs). The immunogenicity and immunotherapeutic effect of the cVLPs vaccine was evaluated in immunized mice and a tumor-bearing mouse model. The results showed that HBc-E765m cVLPs elicited high E5-, E6- and E7- specific CTL and serum IgG antibody responses, and also relatively high levels of the cytokines IFN-γ, IL-4 and IL-5. More importantly, the cVLPs vaccine significant suppressed tumor growth in mice bearing E5-TC-1 tumors. Our findings provide strong evidence that this novel HBc-E765m cVLPs vaccine could be a candidate vaccine for specific immunotherapy in HPV16-associated cervical intraepithelial neoplasia or cervical cancer.

Expected value of artificial intelligence in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

This ESGE Position Statement defines the expected value of artificial intelligence (AI) for the diagnosis and management of gastrointestinal neoplasia within the framework of the performance measures already defined by ESGE. This is based on the clinical relevance of the expected task and the preliminary evidence regarding artificial intelligence in artificial or clinical settings. MAIN RECOMMENDATIONS:: (1) For acceptance of AI in assessment of completeness of upper GI endoscopy, the adequate level of mucosal inspection with AI should be comparable to that assessed by experienced endoscopists. (2) For acceptance of AI in assessment of completeness of upper GI endoscopy, automated recognition and photodocumentation of relevant anatomical landmarks should be obtained in ≥90% of the procedures. (3) For acceptance of AI in the detection of Barrett's high grade intraepithelial neoplasia or cancer, the AI-assisted detection rate for suspicious lesions for targeted biopsies should be comparable to that of experienced endoscopists with or without advanced imaging techniques. (4) For acceptance of AI in the management of Barrett's neoplasia, AI-assisted selection of lesions amenable to endoscopic resection should be comparable to that of experienced endoscopists. (5) For acceptance of AI in the diagnosis of gastric precancerous conditions, AI-assisted diagnosis of atrophy and intestinal metaplasia should be comparable to that provided by the established biopsy protocol, including the estimation of extent, and consequent allocation to the correct endoscopic surveillance interval. (6) For acceptance of artificial intelligence for automated lesion detection in small-bowel capsule endoscopy (SBCE), the performance of AI-assisted reading should be comparable to that of experienced endoscopists for lesion detection, without increasing but possibly reducing the reading time of the operator. (7) For acceptance of AI in the detection of colorectal polyps, the AI-assisted adenoma detection rate should be comparable to that of experienced endoscopists. (8) For acceptance of AI optical diagnosis (computer-aided diagnosis [CADx]) of diminutive polyps (≤5 mm), AI-assisted characterization should match performance standards for implementing resect-and-discard and diagnose-and-leave strategies. (9) For acceptance of AI in the management of polyps ≥ 6 mm, AI-assisted characterization should be comparable to that of experienced endoscopists in selecting lesions amenable to endoscopic resection.

Construction of a diagnostic classifier for cervical intraepithelial neoplasia and cervical cancer based on XGBoost feature selection and random forest model.

The pathological phenotype of early-stage cervical cancer (CC) is similar to that of cervical intraepithelial neoplasia (CIN), which provides a challenge for the diagnosis of cervical precancerous lesions. Meanwhile, the existing diagnostic methods have certain subjectivity and limitations, resulting in the possibility of misdiagnosis or missed diagnosis. Hence, some methods are needed to assist diagnosis of CC and CIN. Based on the data of CIN and CC in gene expression omnibus (GEO) dataset, the eXtreme Gradient Boosting (XGBoost) algorithm was used to screen the feature genes between CIN and CC for constructing the classifier. Incremental feature selection (IFS) curve was also used for screening. The classifier was validated for reliability using principal component analysis (PCA) dimensionality reduction analysis and heat map analysis of gene expression. Then, differentially expressed genes of CIN and CC were intersected with the classifier genes. Genes in the intersection were used as seeds for protein-protein interaction network construction and restart random walk analysis. And the genes with the top 50 affinity coefficients were selected for gene ontology (GO) and kyoto encyclopedia of genes and genome (KEGG) enrichment analyses to observe the biological functions with differences between CIN and CC. The peripheral blood genes of CIN and CC were analyzed, and seven genes were screened. Using this gene for classifier construction, IFS curve screening revealed that the three-feature gene classifier constructed according to the random forest model had the best effect. The results of PCA dimensionality reduction analysis and gene expression heat map analysis showed that the three-gene classifier could effectively distinguish CIN from CC. A three-gene diagnostic classifier can effectively distinguish CIN patients from CC patients and provide a reference for the clinical diagnosis of early CC.

Long-read sequencing reveals oncogenic mechanism of HPV-human fusion transcripts in cervical cancer

Integration of high-risk human papillomavirus (HPV) into the host genome is a crucial event for the development of cervical cancer, however, the underlying mechanism of HPV integration-driven carcinogenesis remains unknown. Here, we performed long-read RNA sequencing on 12 high-grade squamous intraepithelial lesions (HSIL) and cervical cancer patients, including 3 pairs of cervical cancer and corresponding para-cancerous tissue samples to investigate the full-length landscape of cross-species genome integrations. In addition to massive unannotated isoforms, transcriptional regulatory events, and gene chimerism, more importantly, we found that HPV-human fusion events were prevalent in HPV-associated cervical cancers. Combined with the genome data, we revealed the existence of a universal transcription pattern in these fusion events, whereby structurally similar fusion transcripts were generated by specific splicing in E6 and a canonical splicing donor site in E1 linking to various human splicing acceptors. Highly expressed HPV-human fusion transcripts, eg, HPV16 E6*I-E7-E1SD880-human gene, were the key driver of cervical carcinogenesis, which could trigger overexpression of E6*I and E7, and destroy the transcription of tumor suppressor genes CMAHP, TP63 and P3H2. Finally, evidence from in vitro and in vivo experiments demonstrates that the novel read-through fusion gene mRNA, E1-CMAHP (E1C, formed by the integration of HPV58 E1 with CMAHP), existed in the fusion transcript can promote malignant transformation of cervical epithelial cells via regulating downstream oncogenes to participate in various biological processes. Taken together, we reveal a previously unknown mechanism of HPV integration-driven carcinogenesis and provide a novel target for the diagnosis and treatment of cervical cancer.

S891 Risk of Cervical Dysplasia/Cancer in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Introduction: There is inconsistent and conflicting evidence regarding the risk of cervical dysplasia/cancer in patients with inflammatory bowel disease (IBD). This systematic review was conducted to determine the risk of cervical abnormalities in patients with IBD and also estimate the comparative risk with respect to the general population. Methods: We searched various databases for studies which reported about rates of cervical intraepithelial neoplasia(CIN), cervical cancer or high risk HPV in IBD patients. We also extracted the rates of CIN, cervical cancer and high risk HPV in controls. Pooled prevalence of these lesions in IBD and relative risk in IBD patients in comparison to the healthy controls was estimated. We excluded studies which did not provide relevant data. All analysis were done in R version 4.1.1 using the meta and metafor packages. The random effects model was used with inverse variance approach for pooled prevalence and M-H method for calculation of relative risk. Results: We searched Embase, Medline and Pubmed and identified 522 relevant papers on 25th April 2022. Duplicates were removed and after initial screening, 44 papers were selected for full text screening. Eventually, 9 papers (5 case control and 4 cohort studies of 53,781 patients with IBD) were included in the quantitative synthesis. The pooled prevalence of CIN, cervical cancer and high risk HPV in the IBD population was 0.04 (0.01 - 0.11, I2= 100%). Patients with IBD were at a greater risk of cervical dysplasia/cancer when compared with healthy controls (relative risk 3.01, 1.44 - 6.31, I2= 100%). Conclusion: The patients with inflammatory bowel disease are at a heightened risk of developing cervical abnormalities like CIN,cervical cancer and high risk HPV lesions as compared to normal controls. These findings point to the importance of undergoing screening at regular intervals and significance of HPV vaccination in IBD patients in aiding to reduce the risk of developing cervical cancer.

Is it Really Necessary to Perform Colposcopy in Patients with Ascus and HR HPV Positivity?

IS IT REALLY NECESSARY TO PERFORM COLPOSCOPY IN PATIENTS WITH ASCUS AND HR HPV POSITIVITY? INTRODUCTION: Papanicolaou (Pap) smear is a very important screening method for detection of cervİcal cancer or cell changes that can lead to it. Atypical squamous cells of undetermined significance (ASCUS) is the most common abnormality seen among all cervical cytologies with the percentage of 4-5% . Human papillomavirus (HPV) infection is regarded as a major cause of cervical intraepithelial neoplasia (CIN) and cervical cancer. Colposcopy is recommended for all women with high-grade squamous intraepithelial lesion (HSIL) and atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H) for cervical cancer screening . It is also recommended for high-risk HPV (HR HPV) positive women with ASCUS. The aim of this study is to evaluate the importance of colposcopy in patients with ASCUS and HR HPV positivity. MATERIALS AND METHODS: Study Population We performed a retrospective study approved by the ethics committee of Acıbadem University. Women with diagnosis of ASCUS and HR HPV positivity who underwent colposcopic evaluation at 2 different gynecologic oncology clinics of our university from January 2011 to January 2019 were included in our study. The age range was from 21 to 48 and the mean age of patients’ was 29. Subjects who were pregnant, hysterectomized or had previous cytological abnormalities were excluded. CONCLUSION: In this study, we aimed to evaluate the significance of colposcopy in patients with ASCUS and high-risk HPV positivity, especially strains 16 and 18. As mentioned in some other studies, immediate colposcopy is an expensive screening procedure for further evaluation of ASCUS .

Clinical characteristics and a 2-year follow-up of unsatisfactory conventional Pap smears: a retrospective case–control study

The objective of this study was to conduct a 2-year follow-up of individuals having unsatisfactory reports of Pap smears and to analyze the contributing factors. This was a retrospective study at a medical center that performed about 5000–6000 Pap smears annually in Eastern Taiwan. Women who had unsatisfactory results due to scant cellularity between January 1, 2015–December 31, 2016, were included in this study. The control group comprised age-matched women with normal Pap smears at a 1:4 ratio, during the same period. The clinical characteristics and the 2-year outcomes were followed. Patients who were unavailable for follow-up assessments or who had insufficient clinical information were excluded. Student’s t-test and chi-square test were used for continuous and categorical variables, respectively. Statistical significance was defined as a p-value < 0.05. A total of 887 Pap smears were included. A total of 717 and 170 women had normal Pap and unsatisfactory Pap tests, respectively. After excluding women who were unavailable for follow-up, the final analysis included 248 and 67 women with normal and unsatisfactory Pap tests, respectively. The mean age was not significantly different between the two groups (49.97 ± 10.69 and 51.61 ± 11.28 years in the unsatisfactory Pap and control groups, respectively [p > 0.05]). The percentage of menopause and vaginal discharge were significantly different between the two groups. Multivariate analysis revealed that premenopausal status, increased discharge were associated with the risk of unsatisfactory Pap tests. Of the 67 women with unsatisfactory Pap tests, all tested negative for any malignancies at a 2-year follow-up assessment. Women with increased vaginal discharge and without menopause were at an increased risk of having an unsatisfactory Pap test. Our results indicate that an unsatisfactory Pap smear due to scant cellularity might not increase the risk of intraepithelial neoplasia or cancer after 2 years. Further, large-scale studies with longer follow-up periods are required.

Segmentation of the cervical lesion region in colposcopic images based on deep learning.

BackgroundColposcopy is an important method in the diagnosis of cervical lesions. However, experienced colposcopists are lacking at present, and the training cycle is long. Therefore, the artificial intelligence-based colposcopy-assisted examination has great prospects. In this paper, a cervical lesion segmentation model (CLS-Model) was proposed for cervical lesion region segmentation from colposcopic post-acetic-acid images and accurate segmentation results could provide a good foundation for further research on the classification of the lesion and the selection of biopsy site.MethodsFirst, the improved Faster Region-convolutional neural network (R-CNN) was used to obtain the cervical region without interference from other tissues or instruments. Afterward, a deep convolutional neural network (CLS-Net) was proposed, which used EfficientNet-B3 to extract the features of the cervical region and used the redesigned atrous spatial pyramid pooling (ASPP) module according to the size of the lesion region and the feature map after subsampling to capture multiscale features. We also used cross-layer feature fusion to achieve fine segmentation of the lesion region. Finally, the segmentation result was mapped to the original image.ResultsExperiments showed that on 5455 LSIL+ (including cervical intraepithelial neoplasia and cervical cancer) colposcopic post-acetic-acid images, the accuracy, specificity, sensitivity, and dice coefficient of the proposed model were 93.04%, 96.00%, 74.78%, and 73.71%, respectively, which were all higher than those of the mainstream segmentation model.ConclusionThe CLS-Model proposed in this paper has good performance in the segmentation of cervical lesions in colposcopic post-acetic-acid images and can better assist colposcopists in improving the diagnostic level.

Elevated expression of protein-L-isoaspartate O-methyltransferase-1 (PCMT1) in cervical cancer.

BackgroundProtein-L-isoaspartate O-methyltransferase-1 (PCMT1) is a protein carboxyl methyltransferase enzyme, which has been found to play roles in cancers. However, no clinical information about the correlation between cervical cancer and PCMT1 expression has been reported.MethodsWe used immunohistochemistry (IHC) to characterize the protein level of PCMT1 in human cervical intraepithelial neoplasia and cervical cancer specimens. The mRNA expression profile of PCMT1 in cervical cancer was also analyzed by using Gene Expression Omnibus (GEO) databases. The prognostic value of PCMT1 in patients with cervical cancer was evaluated by using the Kaplan-Meier plotter. Gene set enrichment analysis (GSEA) was conducted by using The Cancer Genome Atlas (TCGA) cervical cancer dataset.ResultsThe protein level of PCMT1 was increased in cervical high-grade squamous intraepithelial lesion (HSIL) (7.40±0.42) and cervical cancer tissues (10.70±0.54), compared to normal cervix (5.00±0.86) and low-grade squamous intraepithelial lesion (LSIL) (6.22±0.57) (P<0.05). the immunoreactivity score (IRS) of PCMT1 was also higher in cervical cancer tissues than in paired adjacent non-cancerous cervical tissues (9.03±0.52 vs. 6.32±0.46) (P<0.05). High expression of PCMT1 was associated with decreased overall survival (OS) of patients with cervical cancer (P=0.0022). GSEA demonstrated that cervical cancer patients with high expression of PCMT1 were enriched in the various cancer-related signaling pathways.ConclusionsThese results suggest that PCMT1 might be a diagnostic and prognostic biomarker for cervical cancer, and further validation studies should be performed.

Association between common vaginal and HPV infections and results of cytology test in the Zhoupu District, Shanghai City, China, from 2014 to 2019

BackgroundHPV (human papillomavirus) is an important cause of cervical cancer. Cervical-vaginal infection with pathogens, such as herpes simplex virus (HSV), bacterial vaginosis Trichomonas vaginalis and vaginal candidiasis could be a cofactor. This study aimed to assess the relationship between vaginal infection with HPV genotype and cytology test results and analyze the relationship between vaginal and HPV infections and cervical cancer.MethodsWe performed a district-based study to elucidate the relationship among the vaginal and HPV infections and cervical cancer. We collected the cervical exfoliation data of 23,724 women admitted to the Shanghai Zhoupu Hospital and received ThinPrep cytology test (TCT) and HPV detection between 2014 and 2019.ResultsTotal vaginal infection rate was 5.3%, and the HPV-positive group had a slightly higher vaginal infection rate than the HPV-negative group (P < 0.01). The incidence rate of cervical intraepithelial neoplasia or cervical cancer with vaginal infection was higher than without vaginal infection (P < 0.001).ConclusionHPV/vaginal infection-positive women tended to have abnormal results of TCT. Women with vaginal infection were more likely to develop HPV infection. HSV combined with HPV infection was noted as a causal factor for HSIL.

Photodynamic therapy of cervical intraepithelial neoplasia and cervical cancer

Purpose: to study the effectiveness of photodynamic therapy in combination with diathermoelectroconization in the treatment of cervical intraepithelial neoplasia and cervical cancer.Materials and methods. The study included 108 patients aged 33.13 ± 1.18 years. Human papillomavirus was detected in all patients. The study group consisted of 62 patients with cervical diseases. The fi rst subgroup included 28 patients with moderate to severe cervical intraepithelial neoplasia and pT1AN0M0 cervical cancer who underwent diathermoelectroconization and photodynamic therapy. The second subgroup included 34 patients with severe cervical intraepithelial neoplasia who underwent only cervical diathermoelectroconization. The control group included 46 patients with unchanged cervix. To carry out fl uorescent diagnostics and photodynamic therapy, the patients of the fi rst subgroup were intravenously injected with a solution of photosensitizer “Fotoditazin” (“Vetagrand”, Russia) at a dose of 0.8–1.2 mg/kg. Three hours later, using the AFS device (“Polironik”, Russia), fl uorescent diagnostics was performed followed by photodynamic therapy with an ALHT-ELOMED laser (“Elomed”, Russia) in continuous mode. The wavelength was 662 nm, the output power – 3 W, the radiation dose – 200–300 J/cm2 for the cervix and 100–125 J/cm2 – for the cervical canal. All patients underwent complex antiviral therapy.Results. All patients after photodynamic therapy showed complete eradication of human papillomavirus and regression of cervical intraepithelial neoplasia. Morphological studies have shown that the effectiveness of combined treatment of moderate and severe cervical intraepithelial neoplasia, reaching 100 %, was higher than with the use of diathermoelectroconization alone (95 %). There were no recurrences of cervical intraepithelial neoplasia and cervical cancer after combined treatment.Conclusion. Photodynamic therapy of cervical intraepithelial neoplasia and cervical cancer is a highly effective method.

Risk of human papillomavirus infection and cervical intraepithelial lesions in Chinese renal transplant recipients.

ObjectiveWhile human papillomavirus (HPV) infection in women is associated with cervical intraepithelial neoplasia and cervical cancer, HPV testing is not often performed in routine practice for renal transplantation patients. The genotype-specific prevalence of HPV and risk factors for HPV infection are still unclear.MethodsFrom 2010 to 2020, patients receiving renal transplantation surgery (referred to as RTRs), who had been screened for HPV infection one year after transplantation were enrolled. A comparison cohort of four age- and marital status-matched healthy individuals was selected for RTRs. The clinical characteristics and cervical screening results of RTRs were analyzed.ResultsOur study included 196 female renal transplant recipients (RTRs), none of whom had been vaccinated against HPV. Overall high-risk HPV (hrHPV) infection and abnormal cytology rates in the RTR group were 23.5% and 20.9%, respectively. The odds ratios of hrHPV infection and cervical intraepithelial neoplasia grade 2+ in RTRs vs. non-RTRs were 3.033 (95% CI, 2.013-4.568) and 3.628 (95% CI, 1.863-7.067), respectively. The prevalence of HPV16 in RTRs was much higher (30.4% vs. 8.3%, P=0.002). The multi-infection rate was much higher in HPV-infected RTRs (23.9% vs. 1.14%, P<0.001). The only risk factor for hrHPV infection was the duration of immunosuppression, which increased with time.ConclusionRTRs had significantly higher HPV infection rates and increased risks of HPV-related cervical premalignancies and cancers due to the immunosuppressed state. The duration of immunosuppression is a risk factor for transplant recipients. Female RTRs may benefit from more frequent cervical cancer screening after renal transplantation than healthy women. Prospective research on HPV infection dynamics in RTRs and optimal screening methods should be further explored in the future.

Evaluation of p16/Ki-67 dual-stain as triage test for high-risk HPV-positive women: A hospital-based cross-sectional study.

Most human papillomavirus (HPV)-positive women recover from infections and do not develop cervical intraepithelial neoplasia (CIN) and cervical cancer. Additional triage approaches are needed to reduce unnecessary colposcopy referrals. The aim of this study is to determine the high-risk HPV prevalence in a hospital-based population and to evaluate the performance of p16/Ki-67 dual-stain test for the triage of high-risk HPV-positive women to detect precursor lesions and cervical cancer compared with the ThinPrep cytologic test (TCT). In a hospital-based population, 100,801 women were provided with a primary HPV DNA test and only women with high-risk HPV infections were triaged using TCT and p16/Ki-67 dual-stain test. CIN2 or worse (≥CIN2) or CIN3 or worse (≥CIN3) were defined as the clinical end points. The p16/Ki-67 dual-stain indicated a statistically significant higher sensitivity (82.8% vs. 66.7%%), specificity (51.6% vs. 44.4%), positive predictive value (33.2% vs. 25.8%), negative predictive value (91.2% vs. 82.1%), and accuracy (58.6% vs. 49.4%) compared with TCT examination within ≥CIN2 cases. Similar patterns were observed for the ≥CIN3 end point. Our study demonstrated that p16/Ki-67 dual-stain test could achieve better performance compared with TCT examination for ≥CIN2 or ≥ CIN3 detection, representing a promising approach as a specific and efficient triage strategy for high-risk HPV-positive women.