Infecciones cervicovaginales en la prueba de Papanicolaou de pacientes asintomáticas

Introducción: La prueba de Papanicolaou estudia las células exfoliadas de la unión escamo-columnar del cuello uterino para la detección de células anómalas y también es útil para el diagnóstico de infecciones cervicovaginales. Objetivo: Caracterizar a las pacientes con infecciones cervicovaginales asintomáticas, diagnosticadas por prueba de Papanicolaou. Métodos: Se realizó una investigación observacional, descriptiva y transversal, en 656 pacientes con infección cervicovaginal asintomática, diagnosticadas por prueba de Papanicolaou. Se estudiaron: gérmenes, edad, inicio de las relaciones sexuales, número de compañeros sexuales, anomalías de células epiteliales cervicales. La información se obtuvo mediante interrogatorio, examen clínico y prueba de Papanicolaou. Se utilizaron técnicas de estadística descriptiva para el cálculo de las frecuencias absolutas, porcentajes, media y desviación estándar. Resultado: Se halló un predominio de la vaginosis bacteriana (46 %), seguido de la infección por Candida spp (38,2 %). La edad media de las pacientes fue de 36,4 años. Se observó que en 244 mujeres la edad de inicio de las relaciones sexuales fue de 16 - 20 años (37,2 %). Tuvieron un compañero sexual activo 531 casos (80,9 %). El 86 % no presentó lesiones cervicales, pero el 72,7 % de las infecciones por VPH sí tuvieron. Conclusiones: La generalidad de las mujeres tiene vaginosis bacteriana, son adultas, con inicio precoz de las relaciones sexuales y un compañero sexual activo. Gran parte no presentan lesiones cervicales, la mayoría, con infección por VPH, poseen anomalías de las células epiteliales cervicales.

Introduction: The Papanicolaou test studies the exfoliated cells of the squamo-columnar junction of the cervix for the detection of abnormal cells and is also useful for the diagnosis of cervicovaginal infections. Objective: To characterize patients with asymptomatic cervicovaginal infections diagnosed by Papanicolaou test. Methods: An observational, descriptive and cross-sectional investigation was carried out in 656 patients with asymptomatic cervicovaginal infection, diagnosed by Papanicolaou test. The following were studied: germs, age, initiation of sexual relations, number of sexual partners, anomalies of cervical epithelial cells. The information was obtained through interrogation, clinical examination and Papanicolaou test. Descriptive statistical techniques were used to calculate absolute frequencies, percentages, mean and standard deviation. Result: A predominance of bacterial vaginosis was found (46%), followed by Candida spp infection (38.2%). The average age of the patients was 36.4 years. It was observed that in 244 women the age at which sexual relations began was 16 - 20 years (37.2%). 531 cases (80.9%) had an active sexual partner. 86% did not present cervical lesions, but 72.7% of HPV infections did. Conclusions: The majority of women have bacterial vaginosis, they are adults, with early onset of sexual relations and an active sexual partner. Most of them do not have cervical lesions, the majority, with HPV infection, have anomalies of the cervical epithelial cells.

Tumor de Buschke-Löwenstein en el embarazo adolescente / Buschke-Löwenstein Tumor in Adolescent Pregnancy

Resumen El tumor de Buschke-Löwenstein, también denominado condiloma acuminado gigante, es una entidad rara causada por el virus del papiloma humano (VPH), con una incidencia de 0.01% en la población en general y solo 6 casos reportados en embarazadas. No existe un consenso con respecto al tratamiento; sin embargo, la cirugía es la técnica más descrita. Caso clínico: Paciente primigesta de 14 años, con un embarazo de 21 semanas de gestación, quien ingresó a urgencias por una masa dolorosa en región perineal de 5 meses de evolución. A la exploración física se encontraron en región perineal 2 lesiones exofíticas, coliformes, irregulares, ulceradas de aproximadamente 20 × 10 cm con presencia de secreción amarillenta fétida. Se realizó escisión del tumor con amplios márgenes quirúrgicos y cierre por segunda intención. Por parte de patología se reportó un condiloma acuminado gigante sin lesión en borde quirúrgico. La prueba por PCR detectó el genotipo 53 del virus de papiloma humano. Después de 12 semanas se presentó epitelización completa, sin complicaciones. Conclusión: El tumor de Buschke-Löwenstein es considerado como benigno, no obstante, representa cierto grado de malignidad y tiende a recurrir después del tratamiento, por lo que es importante reforzar las medidas de tamizaje y prevención del Virus del Papiloma Humano.

Abstract Buschke-Löwenstein tumor also called giant condyloma acuminatum is a rare condition due to the human papillomavirus with an incidence of 0.01% and just 6 cases reported in pregnancy. There is no consensus on the treatment, although surgery has been the most reported. Clinical case: A 14 year-old primigravid patient with a 21- week pregnancy who was admitted to the Emergency Department due to a perineal painful tumor which appeared 5 months before. On physical examination two irregular exophytic, cauliflower-like and ulcerated lesions of 20 × 10 cm of size each one with malodorous discharge were found on her perineal region suggestive of giant condyloma acuminatum. We decided to resect the tumor with tumor-free margin control and healing per secundam. The pathology report showed a giant condyloma acuminatum with tumor-free margin. The PCR analysis revealed human papillomavirus genotype 53. Complete epithelialization was noted at 12 weeks with no complications noted. Conclusion: Buschke-Löwenstein tumor is considered as a benign tumor, but it carries a risk of malignant transformation and it can appear after treatment, which makes important to strengthen the prevention and screening of human papillomavirus.

Conhecimento para apoio aos profissionais responsáveis pelo diagnóstico de citologia anal: revisão narrativa e interpretação de critérios citomorfológicos

Resumo:Introdução:O câncer anal é uma patologia considerada rara, apesar de crescente na população. A citologia anal tem sido uma aposta para diagnosticar as alterações pré-neoplásicas, evitando a evolução ao câncer. Objetivos:I) Abordar aspectos de satisfatoriedade da amostra celular e revisar os critérios citomorfológicos dos achados benignos e malignos nos esfregaços de citologia anal. II) Tornar este artigo um instrumento de suporte aos profissionais de saúde que atuam no setor de Citopatologia vinculados ao Sistema Único de Saúde (SUS) ou à iniciativa privada. Métodos:Revisão narrativa, com busca nas bases PubMed, Science Direct e SciELO, de fevereiro a abril/2023. Desenvolvimento:A análise da literatura aponta para a aplicação da citologia anal para diagnóstico das alterações induzidas pelo Papilomavírus Humano (HPV) no canal anal. O rastreamento se baseia na semelhança ao controle do câncer de colo uterino e à história natural da doença, reconhecendo que as lesões precursoras evoluem ao câncer invasivo. Essa janela entre a lesão e o câncer abre espaço para detecção precoce. Oportunamente, a técnica pode diagnosticar agentes responsáveis por outras Infecções Sexualmente Transmissíveis (IST). Conclusão: Qualificar os laudos de diagnóstico citopatológico pode apoiar o cuidado desde a atenção primária. O intuito deste trabalho foi contribuir com o processo de aprendizagem dos profissionais da saúde e apoiar a saúde pública nas estratégias de garantia de cuidado às pessoas.

Distribución de genotipos de virus papiloma humano de alto riesgo en mujeres y hombres atendidos en una red asistencial privada en la Región Metropolitana, Chile / Distribution of high-risk human papillomavirus genotypes in women and men attended in a private healthcare network in the Metropolitan Region, Chile

Introducción: La infección persistente por genotipos de virus papiloma humano de alto riesgo (VPH-AR) es la principal causa del cáncer cérvico-uterino en todo el mundo. Los genotipos 16 y 18 están asociados a la progresión hacia el cáncer de cuello uterino; sin embargo, otros genotipos también presentan alto riesgo oncogénico. Existe escasa evidencia respecto a la distribución de genotipos VPH-AR en la población nacional, siendo un tema que debiese ser abordado en el contexto de un creciente aumento de la inmigración e implementación del programa de inmunización en Chile desde 2015. Objetivo: Dar a conocer la distribución de genotipos de VPH-AR detectados en pacientes de ambos sexos, atendidos en la red de atención privada de Clínica Dávila de Santiago, entre los años 2014 y 2021. Metodología: Se estudiaron muestras genitales y anales provenientes de 3.642 pacientes, incluyendo ambos sexos. La genotipificación fue realizada mediante reacción de la polimerasa en cadena (RPC) en tiempo real (HPV AnyplexTM II HPV28 detection, Seegene, Korea. Resultados: La distribución global de genotipos en mujeres (porcentaje) fue: 16 (14,34%) - 31 (6,20%) - 39 (5,94%) - 58 (5,94%) - 51 (5,68%) - 53 (5,64%) - 52 (5,30%) - 56 (5,27%) - 68 (5,19%) - 66 (4,97% - 18 (3,36%) - 59 (3,29%) - 73 (2,80%) - 35 (2,54%) - 45 (2,13%) - 33 (1,53%) - 82 (1,38%) - 26 (0,49%) y 69 (0,41%). En hombres fue: 16 (8,52%) - 58 (4,39%) - 51 (8,44%) - 26 (0,42%) - 18 (3,21%) - 52 (4,47%) - 39 (5,40%) - 53 (4,56%) - 33 (1,69%) - 35 (2,03%), 73 (2,19%) - 69 (0,59%) - 45 (2,11%) - 59 (4,22%) - 68 (3,04%) - 66 (5,06%) - 31 (4,64%) - 56 (4,81%) y 82 (1,10%). Conclusiones: La distribución de los genotipos de VPH fue concordante con estudios previos nacionales. Se observó una tendencia a la reducción del genotipo 16 en el tiempo, lo cual podría relacionarse a la vacunación, implementada en los últimos años en Chile. Destaca que otros genotipos de VPH-AR tuvieron una alta frecuencia en la población estudiada por lo que sería recomendable evaluar la pesquisa ampliada de genotipos de VPH-AR para valorar el riesgo oncogénico, con fines diagnósticos y terapéuticos.

Background: Persistent infection by high-risk human papillomavirus (HR-HPV) genotypes is the main cause of cervical cancer worldwide. Genotypes 16 and 18 are associated with progression to cervical cancer, however other genotypes also present high oncogenic risk. There is little evidence regarding the distribution of HR-HPV genotypes in the national population, being an issue that should be addressed in the context of a growing increase in immigration and implementation of the immunization program in Chile since 2015. Aim: To show the distribution of HR-HPV genotypes detected in women and men, attended at the private care network of Clinica Davila, Santiago City, between 2014 and 2021. Methods: Genital and anal samples from 3,642 patients were studied, including both sexes. Genotyping was performed by real-time polymerase chain reaction (PCR) (HPV AnyplexTM II HPV28 detection, Seegene, Korea). Results: The global distribution of genotypes in women (percentage) was: 16 (14.34%) - 31 (6.20%) - 39 (5.94%) - 58 (5.94%) - 51 (5.68%) - 53 (5.64%) - 52 (5.30%) - 56 (5.27%) - 68 (5.19%) - 66 (4.97%) - 18 (3.36%) - 59 (3.29%) - 73 (2.80%) - 35 (2.54%) - 45 (2.13%) - 33 (1.53%) - 82 (1.38%) - 26 (0.49%) and 69 (0.41%). In men was: 16 (8.52%) - 58 (4.39%) - 51 (8.44%) - 26 (0.42%) - 18 (3.21%) - 52 (4.47%) - 39 (5.40%) - 53 (4.56%), 33 (1.69%) - 35 (2.03%) - 73 (2.19%) - 69 (0.59%) - 45 (2.11%) - 59 (4.22%) - 68 (3.04%) - 66 (5.06%) - 31 (4.64%) - 56 (4.81%) and 82 (1.10%). Conclusions: The distribution of HPV genotypes was consistent with previous national studies. A tendency to reduce genotype 16 over the years was observed, which could be related to the vaccination, implemented in recent years in Chile. It is remarkable that other HR-HPV genotypes had a high frequency in the population studied, so it would be advisable to evaluate an expanded screening for HR-HPV genotypes to assess the oncogenic risk, for diagnostic and therapeutic purposes.

Detección e integración del virus del papiloma humano de alto riesgo en lesiones pre-neoplásicas en mujeres del sur de Chile: un estudio transversal / High-risk human papillomavirus detection and integration in preneoplastic lesions among women in Southern Chile: a cross-sectional study

INTRODUCCIÓN: El virus del papiloma humano de alto riesgo (VPH-AR) es responsable del cáncer de cuello uterino y sus lesiones preneoplásicas. Los genotipos VPH16 y VPH18 son los más frecuentes en este cáncer. La integración del VPH-AR en el genoma de la célula hospedera es crucial en la carcinogénesis cervical, pero la etapa en que ocurre en la población chilena es incierta. OBJETIVO: Evaluar la integración de VPH16 y VPH18 en lesiones pre-neoplásicas de cuello uterino. MÉTODOS: Se analizaron 108 muestras de raspados cervicales. El VPH se genotipificó mediante reacción de polimerasa en cadena (RPC) e hibridación no radiactiva. La integración de VPH16 y VPH18 se determinó por presencia del gen E2 mediante RPC. RESULTADOS: VPH16 y VPH18 se detectaron en 36,1% y 12,0% de las muestras, respectivamente. El VPH16 se integró en 23,1% de los casos de VPH16, mientras que VPH18 se integró en 100% de las muestras positivas para este genotipo. CONCLUSIONES: La integración VPH-AR es un evento temprano en la carcinogénesis cervical que ocurre en casi la mitad de las lesiones pre-neoplásicas y es más frecuente en VPH18 que en VPH16. La evaluación de la integración VPH-AR puede ser una herramienta útil para detectar el virus en la población chilena.

BACKGROUND: High-risk Human Papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer and its preneoplastic lesions. HPV16 and 18 are the most frequent HR-HPV genotypes detected in cervical cancer. HR-HPV genome integration into the host cell is an important event in the carcinogenic process. However, it remains uncertain which stage of cervical carcinogenesis HPV16 and 18 integration occurs in the Chilean population. AIM: The goal of this study was to evaluate HPV16 and HPV18 integration in preneoplastic lesions of the cervix. METHODS: DNA was extracted from 108 cervical scrape samples with preneoplastic lesions. HPV was genotyped using PCR and non-radioactive hybridization. The integration status of HPV16 and HPV 18 was determined by evaluating the E2 gene presence through PCR. RESULTS: HPV16 and HPV18 tested positive in 36.1% and 12.0% of samples, respectively. HPV16 was found integrated in 23.1% of HPV 16 cases, while HPV 18 in 100% of samples positive for this viral genotype. CONCLUSIONS: HR-HPV integration is an early event in cervical carcinogenesis, occurring in nearly half of preneoplastic lesions and being more frequent in HPV18 than in HPV16. The evaluation of HR-HPV integration can be utilized as a complementary tool for detecting HPV in the Chilean population.

Analysis of HPV vaccine-related KAP and its influencing factors among resident women aged 16-45 years in Pudong New Area / 中国生物制品学杂志

@#Objective To analyze the related knowledge-attitude-practice(KAP)and the influencing factors of human papilloma virus(HPV)vaccine among 16 — 45 year old resident women in Pudong New Area.Methods Six of the 36streets(towns)in Pudong New Area were randomly selected as the survey site,the resident women aged 16 — 45 years were randomly selected excluding those with reading or comprehension disabilities and those with mental disorders,and a total of 1 022 valid questionnaires were collected through self-filling questionnaires to understand the KAP status of the HPV vaccine among the resident women in Pudong New Area. The relationship among KAP of HPV vaccine and its influencing factors were analyzed by univariate analysis and structural equation model.Results The overall awareness rate of HPV vaccine among 16-45 year old resident women in Pudong area was higher. Univariate analysis showed that marital status,educational level,employment status and household annual income were related to the awareness level of HPV vaccine（χ~2=12. 832,17. 636,16. 770 and 20. 030,respectively,each P < 0. 05）;Age,marital status,employment status and children′s status were correlated with HPV vaccination level（χ~2= 12. 382,25. 777,8. 830 and 20. 138,respectively,each P <0. 05）;HPV vaccine health education,HPV and HPV vaccine knowledge scores affected HPV vaccination status（χ~2=97. 561 and 68. 969,respectively,P < 0. 001）;Subjects' knowledge of cervical cancer was positively affected by knowledge of HPV infection(γ_(11)= 0. 756,P < 0. 001). Knowledge of cervical cancer not only positively affected subjects′ attitudes towards the efficacy of HPV vaccine(β_(21)= 0. 557,P < 0. 001),also had a direct effect on the HPV vaccination behavior of the subjects,showing a promoting effect(β_(31)= 0. 274,P = 0. 004). Subjects′ approval of the efficacy of HPV vaccine had a positive effect on their actual vaccination behavior(β_(32)= 0. 175,P = 0. 016).Conclusion The willingness of the 16 — 45 year old resident women in Pudong New Area to inoculate HPV vaccine was positive,but the actual vaccination rate was low. It is suggested to strengthen the HPV vaccine publicity while strengthening the education of cervical cancer and HPV infection,and consider the necessity of including the suitable age males in the scope of human vaccination.

Test of the ability of HPV L1 conserved sequence polypeptide to antisera to degrade HPV6 infection / 中国免疫学杂志

Objective:To determine whether human papillomavirus(HPV L1)C-terminal conserved sequence antibodies with cross-reactive major capsid proteins of different types of HPV L1 have the ability to degrade HPV6 infection.Methods:Condyloma specimens were collected,HPV6 infection cases were identified from the collected samples,and virus was extracted.Polypeptide anti-sera were diluted in different proportions,and then co-cultured and neutralized with the resulting virus,then removed to contact mono-layer-cultured human immortalized keratinocytes and tested by HPV6 disease using PCR.Content of HPV6 DNA in human immortalized keratinocytes was exposed,and the presence of HPV6 L1 protein in this cells was tested by ELISA.Results:Human immortalized ke-ratinocytes infected with HPV6 virus neutralization at different dilution concentrations,the PCR products of their DNA extracts were electrophoresis and showed positive bands of HPV6 specificity zone at 280 bp of the gel,and the intensity of positive bands gradually decreased with increasing antiserum concentration.Protein extracted from human immortalized keratinocytes exposed to anti-serum neutralizing virus was tested by ELISA,and the amount of HPV L1 protein showed the same gradient trend as the above PCR test results,and the difference were statistically significant.Conclusion:It is preliminarily proved that HPV6 L1 conserved sequence polypeptide antisera can partially degrade the infection ability of the virus,and it has the value of studying more HPV neutralization types.

Current status of HPV vaccine uses among adolescents in China / 公共卫生与预防医学

Combining domestic and international studies, an overview of the development of human papilloma virus (HPV) vaccine in the world and China is presented. The current situation of HPV vaccination for adolescents in China is analysed in the light of the latest policies in China, and rationalized recommendations are made to improve the HPV vaccination rate for adolescents in China.

HPV16 E6 mediates oncogenic transformation of cervical epithelial cells by downregulating DHRS2 expression / 陆军军医大学学报

Objective To explore the effects of HPV16 E6 on genes and signaling pathways in cervical epithelial cells and to screen genes associated with oncogenic transformation.Methods HUCEC models infected with HPV16 E6 were constructed,and transcriptome sequencing was performed to screen for differentially expressed genes(DEGs),which were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment to analyze the differential signaling pathways.RT-qPCR was used to validate major differentially down-regulated expressed genes.After predicting the major differentially expressed proteins by molecular docking analysis,the expression of major differential genes in HUCEC cell model was verified by RT-qPCR and Western blotting.In addition,RT-qPCR and Western blotting were used to further verify the expression of major differential genes in cervical cancer cell lines,SiHa and CaSki.Results A total of 55 genes with more than two-fold differential expression were screened.The results centering on down-regulated genes showed that the negatively regulated differential gene was mainly enriched in redox processes;KEGG enrichment analysis revealed that it was mainly associated with carbohydrate metabolism and cancer.RT-qPCR results showed that the down-regulated differential expression trends of the selected 10 genes were basically consistent with the sequencing results.Molecular docking analysis predicted an interaction between DHRS2 and HPV16 E6,and RT-qPCR and Western blotting confirmed that HPV16 E6 down-regulated DHRS2 mRNA(P＜0.01)and protein(P＜0.05)and ETV5 protein expression(P＜0.01).In SiHa and CaSki cells,compared with the control group,the mRNA and protein expression of DHRS2 was downregulated and positively correlated with the trend of P53 protein expression(P＜0.05).Conclusion HPV16 E6 can mediate oncogenic transformation of cervical cells and promote cervical carcinogenesis through downregulating DHRS2 expression.

Prevention and treatment of high-risk human papilloma virus infection from the perspective of "prevention treatment of disease" based on the theory of "circular flow of Qi" / 国际中医中药杂志

The occurrence of cervical cancer in women is closely related to high-risk HPV infection, and timely and effective interruption of high-risk HPV infection is of great significance to prevent the occurrence of cervical cancer. Huang Yuanyou's theory of "circular flow of Qi" emphasizes on the harmonization of the overall Qi flow, which can explain the physiopathology of women. The occurrence of high-risk HPV infection is related to the loss of spleen and earth transportation in the middle Jiao, poor circulation of Qi, and the low resistance of the body to evil, resulting in the malfunctioning of clear and turbid. Based on the theory of "circular flow of Qi" combined with the idea of "prevention treatment of disease", the author proposes to "prevent the disease before it occurs, regulate the middle earth to preserve the correct Qi" and "prevent the disease before it occurs". The principles of prevention and treatment of high-risk HPV infection are "prevent before the disease, regulate the middle earth to preserve the righteousness", "promote and descend to dispel the poisonous evil", and "prevent recurrence after the disease, balance yin and yang and harmonize Qi and blood", in order to provide reference for clinical treatment.

Metabolomics of Siha Supernatant in Cervical Cancer Cells with Down-regulated HPV16 E6/E7 Expression / 昆明医科大学学报

Objective To detecte the differential metabolites and related pathways in Siha cells of cervical cancer by screening the inhibition of HPV16 E6/E7 expression based on 1H NMR metabolomics so as to identify the key metabolic markers involved in the development of high-risk HPV16 cervical cancer.Methods Siha cells were transfected with RNAi fragments to down-regulate the expression of E6/E7,which were divided into the normal control group(Siha cells),no-load group(si-NON),si-E6 group and si-E7 group,and their transfection efficiency was verified.1H NMR metabolomics was used to reveal the differential metabolites involved in interfering E6/E7 expression in Siha cells.Combined with MetaboAnalyst 5.0 online software,differential metabolites and related metabolic pathways were obtained.Results Fluorescence was observed by inverted fluorescence microscope.Western blotting results showed that compared with Siha group,the expression of E6/E7 in si-E6 group and si-E7 group was decreased(F=145.8,P<0.001).After down-regulating the expression of E6/E7,13 common differential metabolites,including Isoleucine,Leucine and valine,were detected.The results of MetaboAnalyst 5.0 online software analysis suggested that the above metabolites were mainly involved in the biochemical synthesis pathway of aminoacyl-trNA,biochemical synthesis pathway of isoleucine,Leucine and valine;There were 10 metabolic pathways of tyrosine,phenylalanine and tryptophan biochemical synthesis.Conclusion After HPV16 infection,changes of glucose and amino acid metabolism can promote the progression of cervical cancer,which provide a theoretical basis for the prevention and treatment of cervical cancer.

Analysis of fertility preservation and HPV negative conversion rate of LEEP by separating the vesicorectal space / 复旦学报（医学版）

Objective To explore the eradication rate of human papillomavirus(HPV)and gestational outcome of patients with high-grade squamous intraepithelial disease of the cervix(HSIL)after loop electrosurgical excision procedure(LEEP)by transvaginal dissection of the vesicorectal form the cervix.Methods A total of 53 patients treated with LEEP by transvaginal dissection of the vesicorectal form the cervix in Obstetrics and Gynecology Hospital,Fudan University from Jan to Dec,2019 were investigated.Clinical information of cervical cytological examination,HPV test and cervical biopsy under colposcopy were followed up for 6,12 and 24 months post-LEEP were collected.HPV infection in these 53 patients were compared before and after LEEP surgery.The rate of successful fertility of the cohort,the HPV conversion rate of patients with hysterectomy and LEEP done were compared.The association between the pathological type and positive surgical margin and the association between HPV infection type and positive surgical margin were analyzed.Results HPV infection rate of was 94.3%(50/53)and the proportion of HPV16 and/or 18 infection was 75.5%(40/53).Mono-HPV infection rate(69.8%,37/53)was significantly higher than mixed HPV infection rate(22.7%,13/53).Thirty-eight patients(71.7%)were found with positive surgical margin in previous LEEP operation.Fifteen patients had recurrence(28.3%)and 40 patients(75.5%)successfully delivered baby after surgery.Postoperative pathology was mainly HSIL,accounting for 66%(30/53),and 28.3%patients(15/53)had no pathological change.Forty cases had satisfying fertility-conservative operation outcome with negative surgical margin,and 38 patients eradicated HPV infection after LEEP,which took up 95%of patients with satisfying fertility-conservative operation.There was no significant difference of positive resection margin rate in between groups of HPV16/18 infection and other types.Five cases had successful delivery(12.5%,5/40)with 1 case of vaginal delivery and 4 cases of cesarean section.Among these 5 cases,3 cases undertook preventive cervical cerclage,with 1 case of vaginal delivery and 2 cases of cesarean sections.Conclusion HPV eradication rate and surgical outcome could be significantly improved by LEEP with transvaginal dissection of the vesicorectal from the cervix,which satisfied the fertility preservation of females at reproductive age.

Application and prospects of ctDNA detection in HPV associated cervical cancer / 实用医学杂志

Circulating tumor DNA(ctDNA)is a kind of cell-free DNA derived from tumors,which carries comprehensive tumor genetic information;Recent studies have found that ctDNA detection can play a role in the early diagnosis,targeted therapy,and prediction of recurrence in tumors.Human papillomavirus(HPV)-associated gynecological malignancies include most cervical cancer,some vulvar cancer,and vaginal cancer.High-risk HPV long-term infection and integration with cell genome are important causes of these cancers.Studies found that the use of ctDNA detection technology to dynamically monitor changes in HPV-ctDNA can provide valuable information for the clinical management and prognosis of these cancers.Thus,HPV-ctDNA is expected to become an biomarker for HPV-associated tumors.

Diagnostic value of HPV-DNA typing combined with serum NLR and DCLK1 for cervical cancer / 中国现代医生

@#Objective To investigate the value of receiver operating curve human papilloma virus(HPV)-DNA typing combined with serum neutrophil lymphocyte ratio(NLR)and bicorticoid kinase 1(DCLK1)levels in the early diagnosis of cervical cancer.Methods A total of 120 patients with early cervical cancer diagnosed in our obstetrics and gynecology department from August 2018 to June 2022 were randomly included as cervical cancer group,and 120 patients with benign lesions were included as benign group.The level of DCLK1 was detected by ELISA;NLR was detected by automatic blood cell analyzer;HPV subtypes in cervical secretions were detected by HPV genotyping gene chip detection system;the cut-off values of serum NLR and DCLK1 levels in the diagnosis of cervical cancer were analyzed by using the receiver operator curve(ROC);four table method was applied to analyze the diagnostic value of HPV-DNA typing,serum NLR,DCLK1 levels alone and in combination for cervical cancer.Results Compared with benign group,the levels of serum NLR and DCLK1 in cervical cancer group were obviously higher(P<0.05).The positive rate of HR-HPV in cervical cancer group was obviously higher than that in benign group(P<0.05).The ROC curve was drawn with serum NLR and DCLK1 levels as test variables,the results showed that the AUC of serum NLR and DCLK1 predicting early cervical cancer was 0.724 and 0.718,respectively,and the cut-off value was 3.08 and 3.32,respectively.HPV-DNA typing combined with serum NLR and DCLK1 detected 18 false positives and 17 false negatives,Kappa value was 0.725,which was consistent with pathological results.The sensitivity,negative predictive value and accuracy of HPV-DNA typing combined with serum NLR and DCLK1 levels in the diagnosis of early cervical cancer were obviously higher than those of HPV-DNA typing,serum NLR and DCLK1 levels alone(P<0.05).Conclusion The results of HPV-DNA typing combined with NLR and DCLK1 in the diagnosis of early cervical cancer are highly consistent with the pathological results,and the sensitivity and accuracy are obviously improved.

Value of HPV DNA,HPV E6/E7 protein and TCT in cervical intraepithelial neoplasia and cervical cancer screening / 中国现代医生

@#Objective To investigate the value of human papilloma virus(HPV)DNA,HPV E6/E7 protein and thin-prep cytology test(TCT)in cervical intraepithelial neoplasia(CIN)and cervical cancer screening.Methods A total of 190 adult women who received early cervical cancer screening in Department of Gynecology,Zhuji People's Hospital from July 2021 to June 2022 were selected as the study objects.HPV DNA,HPV E6/E7 protein and TCT were detected,respectively,and further colposcopic biopsy was performed.The diagnostic efficacy of HPV DNA,HPV E6/E7 protein and TCT in patients with different lesions were compared.Results The positive rates of HPV DNA,HPV E6/E7 protein,TCT and combined detection in CIN3 and cervical cancer patients were significantly higher than those in cervicitis patients(P<0.05).The positive rates of HPV DNA,HPV E6/E7 protein,TCT and combined detection in cervical cancer patients were significantly higher than those in CIN1 patients(P<0.05).The positive rates of HPV DNA,HPV E6/E7 protein,TCT and combined detection in CIN2+ patients were significantly higher than those in CIN1-patients.The sensitivity,specificity,positive predictive value and negative predictive value of HPV DNA,HPV E6/E7 protein and TCT in the diagnosis of high-grade lesions were 90.80%,30.10%,52.32%and 79.48%,respectively.Conclusion HPV DNA,HPV E6/E7 protein and TCT can be used as screening methods for cervical cancer and precancerous lesions,with the combination of the three being the most sensitive.

Expression,purification and immunogenicity evaluation of recombinant HPV58 virus-like particles / 中国生物制品学杂志

@#Objective To prepare recombinant human papillomavirus 58 L1 protein virus-like particles(HPV58 LI VLPs)in Pichia pastoris and immunize mice with the purified product to evaluate the immunogenicity of HPV58 L1 VLPs.Methods The HPV58 L1 multi-copy expression plasmid was constructed and transformed into Pichia pastoris KM71.The highly expressed Pichia pastoris engineering strain was screened and cultured in 5 L fermenter.The expressed HPV58 L1 VLPs were isolated and purified,which were then used to immunize 80 female BALB/c mice at different doses by intraperitoneal injection.After four weeks,the immune effect was evaluated by median effective dose(ED_(50)).Results Restriction analysis results showed that HPV58 L1 expression vectors were constructed correctly.Western blot,amino acid sequencing and transmission electron microscopy(TEM) results showed that HPV58 L1 protein was correctly expressed in Pichia pastoris and could self-assemble into VLPs at a diameter of about 50 nm.After purification by ion exchange and size exclusion chromatography,the HPV58 L1 VLPs reached a purity above 95%,and the ED_(50) in mouse model was 0.009 μg.Conclusion Recombinant HPV58 L1 VLPs with good immunogenicity were successfully prepared by using Pichia pastoris.

Diagnostic Delay in HPV-Related Oropharyngeal Squamous Cell Carcinoma

Abstract Introduction Human papillomavirus-related (HPV +) oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence and presents diagnostic challenges given its unique clinical presentation. Objective The purpose of the present study is to characterize the impact of the unique clinical presentation of HPV-related OPSCC on delays in diagnosis. Methods Retrospective review of presenting symptoms and clinical characteristics of 284 patients with OPSCC treated from 2002-2014. Delay in diagnosis was defined as the presence of any of the following: multiple non-diagnostic fine needle aspirate (FNA) biopsies; two or more courses of antibiotic therapy; surgery with incorrect preoperative diagnosis; evaluation by an otolaryngologist without further workup; or surgery without definitive postoperative diagnosis. Results p16+ tumors demonstrated a distinct clinical presentation that more commonly involved a neck mass (85.1% versus 57.3% of p16-; p < 0.001) and less frequently included odynophagia (24.6% versus 51.7% of p16-; p < 0.001). Patients who experienced diagnostic delay were more likely to have p16+ tumors (77.7% delayed versus 62.8% not delayed; p = 0.006). p16+ primary tumors were more likely to be undetectable by physical examination of the head and neck including flexible laryngoscopy (19.0% versus 6.7% of p16-; p = 0.007) and more frequently associated with nondiagnostic FNA biopsies of a cervical nodal mass (11.8% versus 3.4% of p16-, p = 0.03). Conclusions Compared with non-HPV related OPSCC, the unique clinical presentation and characteristics of HPV+ OPSCC are associated with an increased incidence of diagnostic delay. Targeted education of appropriate care providers may improve time to diagnosis and treatment.

The impact of herbal treatments on cervicovaginal human papillomavirus infection: a systematic review and meta-analysis

SUMMARY OBJECTIVE: This systematic review and meta-analysis aimed to investigate the effects of herbal treatments on cervicovaginal human papillomavirus infection. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Science Direct, and the Cochrane Library until December 2023, following Cochrane guidelines. Data were analyzed using the Review Manager computer program (Version 5.4.1). RESULTS: Five randomized controlled trials involving a total sample size of 662 women were included in the study. The pooled odds ratio for individuals testing negative for human papillomavirus after herbal intervention among human papillomavirus-positive patients was 1.86 (95% confidence interval (CI) 0.64-5.43), according to the fixed-effects model. Three out of the five studies indicated a significant relationship. The relationship between positive human papillomavirus infection and herbal treatments, measured by the fixed-effects model, resulted in a pooled odds ratio of 0.41 (95%CI 0.17-1.01), reporting a significant association (p=0.05). Subgroup analysis revealed a significant reduction in the relationship between herbal treatment and atypical squamous cells of undetermined significance (OR 0.16, 95%CI 0.03-0.88, p=0.04) but no significant impact on the relationship between herbal treatment and low-grade squamous intraepithelial lesion (OR 0.33, 95%CI 0.01-8.77, p=0.51). CONCLUSION: The meta-analysis suggests that herbal treatments reduce human papillomavirus infections. While herbal treatments show a significant reduction in atypical squamous cells of undetermined significance, they do not significantly impact the regression of low-grade squamous intraepithelial lesions.

Clinical and uterine cervix characteristics of women with Mycoplasma and Ureaplasma in genital discharge

SUMMARY OBJECTIVE: The objective of this study was to assess the clinical and uterine cervix characteristics of patients displaying vaginal discharge with positive results for Mycoplasma sp. and/or Ureaplasma spp. METHODS: An analytical cross-sectional study involving women aged 18-45 years was conducted. Microbiological assessments included Ureaplasma and Mycoplasma cultures, as well as human papillomavirus hybrid capture using ecto and endocervix swabs. All tests were two-tailed, and significance was set at p<0.05. RESULTS: Among 324 women, Ureaplasma prevalence was 17.9%, and Mycoplasma prevalence was 3.1%. The Ureaplasma-positive group exhibited a higher frequency of urinary tract infections (39.1 vs. 19%, p=0.002) and human papillomavirus (39.7 vs. 12.8%, p≤0.001) compared with controls. The Mycoplasma-positive group showed a higher frequency of non-contraceptive use compared with controls (66.2 vs. 30.0%, p=0.036). Abnormal colposcopic findings were more prevalent in the Mycoplasma/Ureaplasma-positive group than in controls (positive: 65% vs. control: 35%, p=0.001). Pap smear findings did not differ between the groups. CONCLUSION: Ureaplasma spp. was associated with urinary tract infections and human papillomavirus, while the presence of Mycoplasma sp. was linked to reduced contraceptive use. When analyzing both pathogens together, a higher frequency of abnormal colposcopic findings was observed, with no difference in cytological findings in the positive group.

P53 and pRB induction improves response to radiation therapy in HPV-positive laryngeal squamous cell carcinoma

Abstract Introduction: Patients with Human Papillomavirus (HPV+)-associated Laryngeal Squamous Cell Carcinoma (LSCC) exhibit dramatically improved survival relative to those with HPV-Negative (HPV-) tumors. In this study, the authors aimed to investigate the radiosensitivity of all available confirmed HPV+ and HPV-LSCC cells in vitro and in vivo. Methods: Primary LSCC cells were generated from tumor specimens obtained from patients. Real-time PCR was performed to confirm HPV infection and the expression of HPV-related genes (E6 and E7), p53, and pRB. Clonogenic survival assays, western blotting, and flow cytometry were used to assess radiation sensitivity, apoptosis, and the expression of p53 and pRB. p53 and pRB knockout cells were generated using CRISPR/Cas9 technology. Results: HPV+ LSCC cells displayed enhanced radiation sensitivity compared to HPV- cells. Radiation-induced apoptosis in HPV+ LSCC cells, accompanied by increased levels of p53 and pRB. Knockout of p53 or pRB led to radiation resistance and attenuated radiation-induced apoptosis in HPV+ LSCC cells. In vivo experiments showed similar results, where knockout of p53 or pRB decreased radiosensitivity in tumor-bearing mice. Conclusion: The present findings demonstrated that HPV+ LSCC cells displayed obvious inherent radiation sensitivity, corresponding to increased apoptosis following radiation exposure. Mechanism study showed that the expression of p53 and pRB in HPV+ cells are required for radiation sensitivity. These findings highlight a novel mechanism by which p53 and pRB play key roles in the radiation sensitivity of HPV+ LSCC compared to HPV-LSCC.