Cervical Epithelial Neoplasia Research Articles

Serum miRNA Combined With Transvaginal Color Doppler Ultrasound Diagnosis Clinical Research on Cervical Cancer.

To explore clinical value of miRNA-18a, miRNA-130a, and miRNA-92a combined with transvaginal color Doppler ultrasound (TVCDS) in the diagnosis of cervical cancer (CC). One hundred patients with pathologically confirmed CC (CC group), 100 patients with cervical epithelial neoplasia (disease group), and 100 patients with benign uterine lesions (control group) were selected. TVCDS was performed, and the levels of serum miRNA-18a, miRNA-130a, and miRNA-92a were detected. The systolic blood velocity of the cancer group, the disease group, and the control group decreased sequentially, while the resistance index and pulsatility index increased sequentially. The serum miR-18a, miR-130a, miR-92a, and expression levels of the patients' increased sequentially. Multivariate logistic regression analysis showed that age, high-risk human papillomavirus (HR-HPV) infection, menopause, blood flow RI, serum miRNA-18a, miRNA-92a, and miRNA-130a were the influencing factors of CC. The receiver operating characteristic curve showed that the sensitivity, specificity, accuracy, and area under curve of transvaginal Doppler ultrasound in the diagnosis of CC were 86.43%, 88.01%, 84.32%, and 0.913; serum miR-18a were, respectively, 76.56, 81.30, 80.36, and 0.839; serum miR-130a were 77.88%, 76.97%, 78.32%, and 0.0.864; serum miR-92a were 71.04%, 80.39%, 80.74%, and 0.894; 90.33%, 95.14%, 91.25%, and 0.947, the area under curve of the combined detection of the 3 was greater than that of the single detection. Serum miRNA combined with TVCDS has the advantages of it being noninvasive, and having high sensitivity and high specificity in the diagnosis of CC.

Current approaches in the diagnosis, treatment and prevention of HPV-associated cervical diseases: practical recommendations. A review

Papillomavirus infection is one of the most important infectious diseases of the reproductive system. The genome of human papillomavirus (HPV) transforms the cervical epithelial cells, leading to progressive changes: from cervical epithelial neoplasia to carcinoma in situ and further to invasive cancer. More than 550 000 cases of cervical cancer (CC) are reported yearly. In Russia, the incidence of CC in 2020 decreased for the first time in 20 years, and the average annual rate of increase in incidence was 1.27%. It became possible thanks to the introduction of a new system of diagnosis, treatment, and prevention of cervical cancer, in particular, the introduction of screening and a program of modern methods of diagnosis and treatment. Uniform for all countries, screening cervical diseases aims to diagnose changes in the cervical epithelium that occur due to HPV, which may be silent. Until now, the basis of screening programs was a cytological study (pap-test). Since 2018, most EU countries have switched to primary screening for HPV (HPV test) due to its greater sensitivity compared to the cytological method. No etiopathogenetic methods of HPV therapy have been developed yet. However, numerous studies have described the effective treatment of HPV-associated cervical lesions. It was shown that the most effective is a comprehensive approach involving treatment aimed at abnormal tissues and nonspecific antiviral and immunomodulatory therapy. The basis of the CC prevention strategy, of course, is primary prevention through vaccination. Studies are ongoing on the effectiveness of the new generation of vaccines based on the L2 viral protein and therapeutic vaccines against HPV.

Histopathological study of malignant lesion of Cervix in a tertiary care hospital of Nepal

Background and objectives: Like in other developing countries, cancer of cervix is one of the leading malignancies in women in Nepal. In Nepal cervical pap-smear screening is not done my most of due to lack of awareness. The objective of this study is to find the prevalence of abnormal cervical epithelial lesions.
 Materials and methods: This was a retrospective study of 140 hysterectomy specimen reported from the Department of Pathology, Birat Medical College in Biratnagar. All tissue blocks of cervical tissues were retrieved, stained by Haematoxyline and Eosin (H & E) stain and re-examined. All the case was reviewed by consultant pathologist of Birat medical college.
 Results: In the present study out of 140 cases 08 ie. 5.71% have cervical epithelial neoplasia I. 1.42% cases is of CINII, 0.71 is of CINIII and 2.85% is squamous cell carcinoma.
 Conclusion: This study has demonstrated that 10.69% of the examined cases were abnormal. The squamous cell carcinoma is leading cancer in our study ie. 2.85%. In developing countries if patient is detected with abnormal pap smears then hysterectomy is indicated.

Cervical Pap smear: A retrospective study on symptomatic women in a tertiary care hospital.

Background: Cancer of the cervix is an increasing health problem and an important cause of mortality in womenworldwide. Cervical cancer ranks 2nd most common visceral cancer in females and stands 3rd in causing death in women inthe world. Pap smear is used as primary screening test for detection of early cervical epithelial changes, cervical epithelialneoplasia and early stage of invasive cervical cancer. Recommendations for Pap smear generally starts around 21 years ofage or within 3 years of onset of sexual activity and thereafter every 3 yearsMethods: This retrospective study was conducted on 100 patients to evaluate all previously reported cervical smearsin the Department of Pathology GMC Kathua, who came with different gynaecological complaints in GynaecologicalOPD at GMC Kathua, J&K.Smears were obtained with the help of Ayre’s spatula and cytobrush to collect specimen fromtransformation zone. The cellular material is quickly spread on 2 clean glass slides and fixed immediately by immersingthem in copulin jar containing 95% ethyl alcohol. The smears were stained with Papanicolaou stain. After mounting theslides with DPX and examined under light microscope , they are reported by pathologists according to Revised BethesdaSystem.Conclusion: Pap smear test is a simple, inexpensive, non -invasive and an OPD performed to detect various premalignantand malignant lesions of cervix. By conducting health camps, increasing awareness programmes and performing Papsmears, the incidence of cervical cancer can be greatly reduced.

Bioinformatics analysis of the transcriptional expression of minichromosome maintenance proteins as potential indicators of survival in patients with cervical cancer

BackgroundAs major regulators of DNA replication in eukaryotes, minichromosome maintenance (MCM) proteins play an important role in the initiation and extension of DNA replication. MCMs and their related genes may be new markers of cell proliferation activity, which is of great significance for the diagnosis and prognosis of cervical cancer.MethodsTo explore the role of MCMs and their related genes in cervical cancer, various bioinformatics methods were performed. First, the ONCOMINE and UALCAN databases were used to analyze the mRNA expression of different MCMs. The Human Protein Atlas database was used to analyze the protein expression of MCMs in normal and tumor tissues. The potential clinical value of MCMs was evaluated using the UALCAN, Kaplan-Meier plotter and cBioPortal databases. Then, the related genes and key coexpressed genes of MCMs were screened using GEPIA2 and cBioPortal analysis. For these genes, we used Metascape and the DAVID database to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, construct the related molecular interaction network, and obtain the key subnetworks and related hub genes. The Kaplan-Meier plotter database was used for survival analysis of cervical cancer patients to evaluate and predict the potential clinical value of the hub genes. Moreover, multiple gene comparisons of the expression of MCMs and related genes in different cancer types also showed the clinical significance of these potential targets.ResultsThe mRNA and protein expression of MCMs increased in tumor tissue. Overexpression of MCM2/3/4/5/6/7/8/10 was found to be significantly associated with clinical cancer stage. Higher mRNA expression levels of MCM3/5/6/7/8 were found to be significantly associated with longer overall survival, and higher mRNA expression of MCM2/3/4/5/6/7/8 was associated with favorable OS. In addition, a high mutation rate of MCMs (71%) was observed. MCM2, MCM4, MCM8, MCM3 and MCM7 were the five genes with the most genetic alterations. In addition, the coexpressed genes and related genes of MCMs were successfully screened for enrichment analysis. These genes were significantly enriched in important pathways, such as the DNA replication, cell cycle, mismatch repair, spliceosome, and Fanconi anemia pathways. A protein-protein interaction network was successfully constructed, and a total of 13 hub genes (CDC45, ORC1, RPA1, CDT1, TARDBP, RBMX, SRSF3, SRSF1, RFC5, RFC2, MSH6, DTL, and MSH2) from 4 key subnetworks were obtained. These genes and MCM2/3/4/5/6/7/8 might have potential clinical value for the survival and prognosis of cervical cancer patients.ConclusionsThese findings promoted the understanding of the MCM protein family and clinically related molecular targets for cervical epithelial neoplasia and cervical cancer. Our results were helpful to evaluate the potential clinical value of MCMs and related genes in patients with cervical cancer.

Analysis of the results of combined treatment of cervix precancerous pathology in reproductive aged women

Aim of the study. Comparative analysis of the results of cervical epithelial neoplasia (CIN) I and II levels (p16ink4a-negative) (LSIL in LAST terminology) treatment against the background of highly oncogenic HPV infection using cold plasma ablation and immunomodulatory therapy with Аllokin-alpha.Materials and methods. We examined 60 women who received treatment for CIN I and CIN II (p16ink 4A negative) at the Multidisciplinary Medical Center of Odessa National Medical University. All women were of reproductive age, had mild dysplasia, high-risk HPV infection (HPV 16, 18, 31, 45) and histological confirmation of CIN I and CIN II (p16ink 4A negative). The patients were divided into 2 groups: 1 (main) group consisted of 30 women who received cold plasma ablation of cervical dysplasia in combination with immunomodulatory therapy with Аllokin-alpha (1 mg subcutaneously every other day, 3 injections before surgery and 3 injections after ablation), Group 2 (control) consisted of 30 patients who received standard cold plasma ablative treatment without prescribing immunomodulators. All women underwent cytomorphological examination of the cervical epithelium, HPV testing by RealTime PCR and colposcopy with mandatory targeted biopsy at the preoperative stage.Results. The use of combined cold plasma ablative treatment of CIN I and CIN II (p16ink 4A negative) in combination with the administration of the immunomodulator Аllokin-alpha significantly reduced the duration of discharge after ablation to 5.44 ± 1.03 days (95% CI: 4.96–6.05), the timing of epithelialization is up to 29.31 ± 1.12 days (95% CI: 26.81–32.32), and to exclude cases of recurrence of genital warts and cervical keratosis. Chances of HPV elimination 6 months after treatment (OR – 5.48; 95% CI: 1.56–29.03; p = 0.0075) and 12 months after treatment (OR – 15.48; 95% CI : 2.05–136.45; p = 0.0094), significantly higher with the combined with immunomodulation method of treatment, in contrast to only cold plasma ablation.Conclusion. Combined, with the use of cold plasma ablation and immunomodulation by perioperative management of Аllokin-alpha, LSIL treatment against the background of highly oncogenic HPV infection in women of reproductive age is accompanied by better functional results, compared with the use of cold plasma ablation alone: reduction in the duration of discharge, acceleration of epithelialization, normalization of the colposcopic and cytologic picture, decrease in the frequency of relapses, a significant increase in the frequency of HPV elimination.

Analysis of risk factors of positive surgical margin and residual lesions after cone resection of high-grade intraepithelial neoplasia

Objective To analyze the risk factors of positive surgical margin and residual lesions after cone resection of high-grade intraepithelial neoplasia, and to guide clinical work and follow-up. Methods The clinical data of 180 patients with cervical epithelial neoplasia of grade Ⅱ and Ⅲ who underwent cervical conization in the People's Hospital of Inner Mongolia Autonomous Region from November 2013 to November 2018 were retrospectively analyzed.The risk factors associated with residual margin and reoperation (including re-cone and hysterectomy) after conization were performed by single factor and multivariate regression analysis. Results The incidence of positive resection margins after conization was 31.67%(57/180), which of the residual margin of re-surgery was 36.84%(21/57). Menopause, contact bleeding, cervical cancer(in situ carcinoma, microinvasive carcinoma) were positive risk factors for conical cutting margin (OR=2.342, 2.428, 8.949). Contact bleeding, cervical cancer(in situ carcinoma, microinvasive carcinoma) were risk factors for residual resection of the surgical margin after conization (OR=5.370, 10.992). Conclusion Contact bleeding, cervical carcinoma in situ, microinvasive carcinoma are closely related to cervical margin and lesion residual.Among them, menopause is also positively related to margin, which is a risk factor affecting cervical cone cutting margin and residual reoperation.It should be highly valued in clinical. Key words: Cervical intraepithelial neoplasia; Conization; Reoperation; Regression analysis; Risk factors

RELATIONSHIP BETWEEN METALLOPROTEINASE AND TIMP1 EXPRESSION AND INTENSITY OF CERVICAL INFLAMMATORY REACTION IN WOMEN OF DIFFERENT AGE GROUPS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA AND MICROINVASIVE CARCINOMA

Objective : to study the relationship between metalloproteinases and expression TIMP1 expression and intensity of inflammatory response in the cervical stroma of women with cervical intraepithelial neoplasia and microinvasive carcinoma. M at erial and methods . Morphological, morphometric and immunohistochemical examination of cervical biopsies in patients with cervical epithelial neoplasia (cINI–III) and microinvasive carcinoma was carried out. all patients were divided into two age groups: group 1 consisted of 95 patients of early reproductive age ranged from 18 to 35 years (mean age 28.5 ± 0.58 years) and group 2 consisted of 85 perimenopausal and menopausal patients aged 49 to 65 (mean age 55.4 ± 0.98 years). Results . In women of both age groups, the density of inflammatory cell infiltrate was shown to increase, being significantly higher in women of group 1 than in women of group 2. the increase in the expression level of metalloproteinases-2, -3, -7, and -9 with dysplasia progression was observed in women of both age groups, being also higher in group 1 women. the tIMP1 expression level was higher in group 2 women and increased with disease progression. Conclusion . In young women, pronounced and active inflammation in the cervical stroma contributes to a high potential for metalloproteinase synthesis. a higher level of tIMP1 expression in perimenopausal and menopausal women may be one of the factors contributing to a decrease in the metalloproteinase synthesis in these women.

Comparison of different human papillomavirus (HPV) vaccine types and dose schedules for prevention of HPV-related disease in females and males.

Comparison of different human papillomavirus (HPV) vaccine types and dose schedules for prevention of HPV-related disease in females and males.

The use of colposcopic punch biopsy in the management of abnormal cervical cytology: a 5–year retrospective audit

The aim of this study was to determine the accuracy of colposcopic punch biopsy to detect cervical epithelial neoplasia (CIN) II + in patients with abnormal cervical cytology and the major colposcopic findings in patients who underwent a loop electrosurgical excision procedure (LEEP), subsequently. A total of 231 patients with abnormal cervical cytology who underwent a colposcopy guided cervical biopsy and subsequent LEEP were analysed. The mean age was 33.4 ± 8.7 years. CIN II + rate on LEEP pathology was significantly higher in patients with high-grade cytology, compared to those with a low-grade cytology (92 vs. 55%, p < .0001). CIN II + was found in 80, 98 and 100% of colpocopic biopsies of patients with LSIL, HSIL and AGC, respectively. The overall concordance rate between a colposcopic biopsy and LEEP was 41% with a kappa coefficient. The overall underestimation of CIN II + was 10.5%. On a patient-based analysis, the sensitivity, specificity, PPV and NPV of colposcopic biopsy were 89.4, 47.1, 79.5 and 66%, respectively. More than two cervical biopsies had 100% sensitivity for CIN II + on LEEP pathology. The specificity and PPV decreased with increasing number of cervical biopsies. A see-and-treat strategy may be considered for high-grade cytologies. Patients with a low-grade cytology should be managed with more than two colposcopic biopsies.

Abstract 1417: Expression of BARD1δ induces genetic instability and is associated with cervical carcinogenesis

Abstract Cervical cancer is always linked to infection with the human papilloma virus (HPV), which causes hyper-proliferation of cervical epithelial cells and neoplasia and cervical cancer. The viral oncoprotein interaction with host tumor suppressor proteins partially explains the uncontrolled proliferation, which ultimately progresses to cervical cancer. However, little is known about the specific factors that promote or inhibit the malignant transformation. Since a portion of HPV infections never evolves into cancer, the identification of discriminatory factors would be an important step towards the development of prognostic and therapeutic tools. Based on this notion, we investigated whether an isoform of BARD1, BARD1δ, which we found frequently expressed in cancer cells, plays a role in the malignant transformation of cervical epithelial cells. Using immunohystochemistry staining on tissue sections and RT-PCR we found that BARD1δ is expressed in proliferating cervical cancer cells, while normal BARD1 is repressed. BARD1 might be a driver of carcinogenesis and might be a critical event in the progression from hyper-proliferating cervical epithelium after HPV infection to cervical cancer. Together, our results show that an isoform of BARD1, BARD1δ, is increasingly expressed in precancerous stages of cervical cancer and the specific inhibition of BARD1δ may represent a novel approach for therapeutic interventions to prevent cervical carcinogenesis after HPV infection. Citation Format: Maxim Pilyugin, Pierre-Alain André, Nicole Concin, Gerda Hofstetter, Irmgard Irminger-Finger. Expression of BARD1δ induces genetic instability and is associated with cervical carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1417. doi:10.1158/1538-7445.AM2017-1417

Recidivas de lesiones pre-malignas de cérvix en pacientes tratadas con cono leep

Introducción: El cáncer cervicouterino, ocupa el primer lugar en incidencia en el Perú y en países en vía de desarrollo y es la segunda causa de muerte por cáncer en la mujer. El tamizaje mediante la citología de Papanicolaou y el oportuno tratamiento de la lesión preinvasora permite una curación cercana al 100%. Objetivos: Determinar el porcentaje de pacientes con diagnóstico de neoplasia intraepitelial cervical, tratadas con cono Leep, que presentaron recurrencia posterior al tratamiento. Diseño: Estudio descriptivo, retrospectivo. Lugar: Servicio de Oncología Ginecológica y Mama, Hospital Nacional Arzobispo Loayza, Lima, Perú. Participantes: Pacientes con diagnóstico de neoplasia intraepitelial cervical y tratadas con cono leep. Intervenciones: Se revisó las historias de 74 pacientes con diagnóstico de neoplasia intraepitelial cervical y que fueron tratadas con cono Leep en el quinquenio 2003 a 2007. Principales medidas de resultados: Recurrencia de la lesión. Resultados: Del total de pacientes, 13 (17,6%) presentaron recurrencia y la mayoría dentro de los dos primeros años de seguimiento. Conclusiones: Se presentó recurrencia de la neoplasia intraepitelial cervical en mayor porcentaje que otros estudios. Existió relación importante entre la edad al momento del diagnóstico, la edad de la primera relación sexual y el número de parejas sexuales. Al término del estudio, todas las pacientes se encontraban libres de enfermedad.

The synergistic therapeutic effect of cisplatin with Human papillomavirus E6/E7 short interfering RNA on cervical cancer cell lines in vitro and in vivo

Human papillomavirus (HPV) types 16 and 18 are the major etiologic factors in the development of cervical epithelial neoplasia. Our study was designed to validate antiviral short interfering RNA (siRNA) targeting the E6 and E7 oncogenes as a potential chemosensitizer of cisplatin (cis-diaminedichloroplatinum II; CDDP) in cervical carcinoma. Specifically, the therapeutic efficacy of combination of CDDP and E6/E7-specific siRNA was assessed in an in vivo cervical cancer xenograft models. The combination of CDDP and E6/E7-specific siRNA had greater efficacy than the combination of CDDP and E6-specific siRNA especially in terms of inducing cellular senescence. Through in vitro and in vivo experiments, the mechanism of synergy between these two treatments was revealed, demonstrating that the combination of E6/E7-specific siRNA and CDDP therapy was significantly superior to either modality alone. In vitro, long-term exposure of HeLa cells to the combination of CDDP and E6/E7-specific siRNA induced apoptosis and cellular senescence. In vivo, E6/E7-specific siRNA potentiated the antitumor efficacy of CDDP via induction of apoptosis, senescence and antiangiogenesis. Our results suggest that E6/E7-specific siRNA may be an effective sensitizer of CDDP chemotherapy in cervical cancer.

Value of HPV-DNA test in women with cytological diagnosis of atypical glandular cells (AGC)

ObjectiveThis study analyzed whether HPV (human papillomavirus) testing contributes towards defining histological abnormalities in women with atypical glandular cells (AGC) diagnosed at cervical cytology. Study designOne hundred and eight women with conventional cervical cancer screening smears suggestive of AGC not otherwise specified (AGC-NOS) and favor neoplastic (AGC-FN) were consecutively enrolled. All women underwent colposcopic examinations and biopsy was performed according to the cytopathologic and/or colposcopic abnormalities present. All specimens were tested for high risk HPV genotypes by Roche's polymerase chain reaction reverse line blot assay. The chi-square test was used to evaluate the association between HPV findings and a diagnosis of high-grade pre-invasive or invasive disease (CIN 2 or worse) taking negative tests or CIN 1 as a reference. Odds ratios (OR) with their respective 95% confidence intervals (95%CI) were used to evaluate the magnitude of the association between HPV testing and CIN 2 or worse. Sensitivity, specificity and their respective 95% confidence intervals (95%CI), positive predictive values (PPV) and negative predictive values (NPV) were also calculated. ResultsFinal diagnosis revealed a negative outcome in 80 cases (74%), cervical epithelial neoplasia 1 (CIN 1) in 13 cases (12%), CIN 2 or worse in 12 cases (11%) and glandular neoplasia in 3 (3%) cases. The overall detection rate of HPV was 21% (23/108). Neoplasia was significantly associated with positive HPV-DNA in women with AGC-NOS (OR=15.21; 95%CI: 2.64–87.50); however, there was no significant association between a histological diagnosis of neoplasia and HPV positivity in women with AGC-FN (OR=3.00; 95%CI: 0.36–24.92). The sensitivity, specificity, positive predictive value and negative predictive value of HPV-DNA testing for the detection of CIN 2 or worse in women with AGC-NOS were 71%, 86%, 29% and 97%, respectively. In women with AGC-FN, these values were 50%, 75%, 66% and 60%, respectively. ConclusionsHPV testing at the time of colposcopy for patients with AGC in whom no colposcopic abnormality is found may be a powerful ancillary tool for identifying women at a high risk of underlying significant cervical lesions.

O537 Data analysis of 18 cases of the pregnancy with cervical epithelial neoplasia

International Journal of Gynecology & ObstetricsVolume 107, Issue S2 p. S246-S246 Free communication (oral) presentations O537 Data analysis of 18 cases of the pregnancy with cervical epithelial neoplasia Z. Liu, Z. LiuSearch for more papers by this authorT. Lu, T. LuSearch for more papers by this authorQ. Liao, Q. LiaoSearch for more papers by this author Z. Liu, Z. LiuSearch for more papers by this authorT. Lu, T. LuSearch for more papers by this authorQ. Liao, Q. LiaoSearch for more papers by this author First published: 06 October 2011 https://doi.org/10.1016/S0020-7292(09)60910-3Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume107, IssueS2Abstracts of XIX FIGO World Congress of Gynecology and ObstetricsOctober 2009Pages S246-S246 RelatedInformation

P16INK4A in routine practice as a marker of cervical epithelial neoplasia

ObjectiveThe aim of this study was to validate the role of p16INK4a immunocytochemistry as a marker of cervical epithelial neoplasia in cytology and biopsy samples. MethodsDuring the period of 4 years a total of 501 immunocytochemistry stains in cytology and biopsy samples were performed. The cytology smears were obtained from two independent laboratories of women with low-grade squamous intraepithelial lesion interpretation of Pap test or ThinPrep. Additionally, a selection of paraffin blocks from cases diagnosed previously with squamous intraepithelial lesion and cervical cancer were immunostained. ResultsAmong 312 cytology samples analyzed by immunocytochemistry, 36.2% were positive for p16INK4a. Negative cases were followed-up with conventional Pap smear and 86.9% showed regression. Among positive patients, 14 underwent surgery and 100% exhibited squamous intraepithelial lesion. In additional immunohistochemical analysis of selected biopsies from our archive, we found that the ratio of positivity for p16INK4a increased from 40% in L-SIL/CIN1 to 69.8% in H-SIL/CIN2 to 100% in H-SIL/CIN3 and squamous cell carcinoma. A relatively low number (24%) of cases with squamous metaplasia revealed focal and/or sporadic staining in the superficial layers of the epithelium. All the cases of cervical adenocarcinoma and mesonephric carcinoma were positive for p16INK4a. Conclusionp16INK4a is a useful additional marker for interpretation of problematic Pap smears and reduces the variability during evaluation of suspicious biopsies of the uterine cervix.

Human Papillomavirus and Papanicolaou Tests to Screen for Cervical Cancer

Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown. In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated. At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy. The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations. (ClinicalTrials.gov number, NCT00479375 [ClinicalTrials.gov].).

High-risk cervical epithelial neoplasia grade 1 treated by loop electrosurgical excision: follow-up and value of HPV testing

This study was undertaken to evaluate the value of high-risk human papillomavirus (HPV) testing in the follow-up of cervical intraepithelial neoplasia grade 1/low-grade squamous intraepithelial lesion treated by loop electrosurgical excision procedure because of the risk criteria established by the American Society for Colposcopy and Cervical Pathology (ie, unsatisfactory colposcopy or positive endocervical curettage, persistence of cervical intraepithelial neoplasia grade 1/low-grade squamous intraepithelial lesion, or high-risk HPV infection for longer than 2 years and older than 40 years). Seventy-seven women with cervical intraepithelial neoplasia grade 1/low-grade squamous intraepithelial lesion treated by loop electrosurgical excision procedure and followed-up with colposcopy, cytology, and high-risk HPV detection using Hybrid Capture II. More than 67% (67.6%) of women had cervical intraepithelial neoplasia grade 1 in the specimen; 22% a cervical intraepithelial neoplasia grade 2-3; and 10.4% had no lesion. Pretreatment HPV testing was positive in 100% of cervical intraepithelial neoplasia grade 2-3, in 93.5% of cervical intraepithelial neoplasia 1, and in 14.3% of cases with no lesion (P < .01). Pretreatment high-risk HPV testing was positive in all cases eventually developing residual/recurrent disease. Fifty percent of women with pretreatment viral load more than 100 relative light units had residual/recurrent disease develop. Posttreatment high-risk HPV testing during the follow-up reached a sensitivity and negative predictive value of 100% for detecting residual/recurrent disease. Patients with low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 and risk factors have a significant risk of harboring a cervical intraepithelial neoplasia grade 2-3 lesion. A conservative approach should be considered when basal high-risk HPV test is negative. High pretreatment high-risk HPV loads should be considered a risk factor for developing residual/recurrent disease. Posttreatment Hybrid Capture II has an extremely high sensitivity for detecting recurrences.

Human Papillomavirus Infection and Polymorphism of p53 codon 72 in the Uterine Cervical Neoplasia

Objective : The uterine cervical neoplasia is one of the most frequent gynecologic tumor in Korean women. Though the precise pathogenic mechanisms were not elucidated, human papillomaviruses (HPVs) has been considered as a strong candidate for the cause of uterine cervical neoplasm. Methods : About 100 subtypes of HPV were known, and they were divided into two groups as “high-risk HPVs” and “low-risk HPVs” according to their oncogenic potentialities. It was known that arginine (Arg) residue at codon 72 of p53 tumor suppressor gene could be used as a marker for the risk of cervical epithelial neoplasia associated human appilloma virus infection. But the notions are still controversal. Studies to date have focused mainly on Caucasians despite marked ethnic variations in both the p53 polymorphism and the different genotypes of human papillomavirus associated with cervical neoplasia. In this study, the p53 codon 72 status in 125 Korean women with cervical neoplasia and 200 Korean healthy women was determined. In addition, the different genotypes of human papillomavirus associated with cervical neoplasia was also determined by DNA Chip. Results : The most frequent subtypes of HPV associated with uterine cervical neoplasia in Korean women were 16 (25.6%), 58 (16%), other type (10.4%), 52 (10%) and 18 (4.8%) in order of frequency. The polymorphic rate of p53 codon 72 in 200 Korean women was Arg/Ar (47%), Arg/Pro (43%) and Pro/Pro (10%) respectively. The polymorphic rate of p53 codon 72 in HPV associated uterine cervical neoplasia was Arg/Ar (55.5%), Arg/Pro (38.9%) and Pro/Pro (5.50%) respectively, which was not statistically significant compared to the normal control. In 16/18 genotypes associated cervical neoplasia, the polymorphic rate of p53 codon 72 was 44.8% (Arg/Arg), 42.1% (Arg/Pro) and 13.1% (Pro/Pro) respectively, while in 58/52/other type/33/35/40/44 genotypes, it was 36.5% (Arg/Arg), 50% (Ar/Pro), and 13.5% (Pro/Pro) respectively. There was no statistical significance between two groups. Conclusion : Above results showed that the genotypes of HPV associated with uterine cervical neoplasia in Korean women were different from those of Western countries, and there was not significant difference between the polymorphism of p53 codon 72 and genotypes of HPV associated with uterine epithelial neoplasia.

The cellular response associated with cervical intraepithelial neoplasia in HIV+ and HIV- subjects.

This study investigates local alterations in T-cell and macrophage subsets that occur in cervical epithelial neoplasia (CIN), in the presence and absence of human immunodeficiency virus (HIV) infection. Ectocervical biopsies from 10 women with CIN who were infected with HIV, and 10 women with CIN but no HIV infection were studied by immunocytochemistry. Significantly increased proportions of activated CD8+ T cells were seen in all CIN biopsies, and these proportions were further increased in the presence of HIV infection. Levels of CD8+TIA-1+ cells were particularly increased in the CIN+HIV+ group. There was a lack of expression of CD28 on the CD8+ cells of the epithelium of CIN+HIV+ samples. A significant reduction in the proportion of epithelial inductive D1+ macrophages and an increase in D1+D7+-suppressive cells were observed in the CIN+HIV+ cohort. The lack of expression of CD28 on the CD8+ cells of the epithelium of CIN+HIV+ samples in combination with the reduced CD4+ T-cell numbers seen in the presence of HIV infection may contribute to the development of higher grade CIN in this susceptible group. This may be aggravated by the reduction in the D1+ epithelial inductive macrophages, which might reflect recruitment of more suppressive D1+D7+ cells. This would further compromise the ability of the local T-cell system to respond to antigens and thus contribute to the development of neoplasia at this site. These results suggest that the increase in activated CD8+ T cells is a consequence rather than a cause of CIN.