Comparison of Hybribio-H13 and Hybrid Capture® 2 human papillomavirus tests for detection of CIN2+ and CIN3+ / Comparación de las pruebas para el virus del papiloma humano Hybribio-H13 y Hybrid Capture® 2 para la detección de NIC2+ y NIC3+

Introduction. Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. Objective. To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). Materials and methods. Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. Results. Therelative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT < 0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test. Conclusion. The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.

Introducción. Se necesitan pruebas para detectar genotipos de VPH de alto riesgo, precisas y de bajo costo, para la tamización del cáncer de cuello uterino en entornos de recursos limitados. Objetivo. Comparar el desempeño de la prueba de bajo costo Hybrid-H13 con la de Hybrid Capture® 2para detectar NIC2+ y NIC3+. Materiales y métodos. Se analizaron en ciego muestras de la línea base provenientes de mujeres del estudio ASCUS-COL, entre los 20 y los 69 años, con diagnóstico dirigido por biopsia-colposcopia de NIC2+ (n = 143), NIC3 + (n = 51) y < NIC2 (n = 632) con la prueba para detección de virus de papiloma humano Hybribio-H13. Estas muestras fueron previamente evaluadas con la prueba Hybrid Capture® 2. Resultados. La sensibilidad relativa de Hybribio-13 versus la de Hybrid Capture® 2 para detectar NIC2+ fue de 0,89 (IC90%: 0,80-0,98; NIT = 0,66) y para NIC3+ fue de 0,92 (IC90%: 0,85-0,98; NIT = 0,35). La especificidad relativa fue de 1,19 (IC90%: 1,05-1,33; NIT < 0,00001). En el análisis restringido a mujeres mayores de 30 años, la sensibilidad relativa de Hybribio-H13 para NIC3+ estuvo marginalmente por debajo de la unidad (proporción = 0,97; IC90%: 0,95-0,99) y la especificidad permaneció más alta que la de la prueba Hybrid Capture® 2. Conclusión. La prueba de Hybribio-H13 fue tan específica como la de Hybrid Capture® 2, pero menos sensible para detectar NIC2+ o NIC3+. Teniendo en cuenta estos resultados y la temprana edad de la población reclutada en la tamización por la presencia de ASCUS en la citología, se sugiere continuar con la evaluación de la prueba Hybribio-H13 para la detección de cáncer de cuello uterino en poblaciones con las mismas características que las de la aquí evaluada.

Unveiling the uncommon: invasive adenocarcinoma cervix presenting during pregnancy: a rare case report

Adenocarcinoma of the cervix presenting during pregnancy is an exceedingly rare occurrence, and the optimal management approach remains uncertain due to limited reported cases. Here we are presenting a case of a multiparous lady who presented with complaints of amenorrhoea for 3 months, pain abdomen, spotting per vaginum, mass felt per vaginum. Ultrasonography showed single live intrauterine pregnancy at 11 weeks 4 days of gestational age with an ill-defined hyperechoic lesion measuring 4.36×4.92×4.16 cm in cervix. HPE of cervical biopsy confirmed cervical adenocarcinoma-endocervical type, grade 2. On MRI, a heterogeneous exophytic irregular mass involving the external os, protruding into the upper vaginal cavity was identified with infiltration into the anterior upper vaginal wall, pelvic lymphadenopathy, and sub-centimetric inguinal lymph nodes were observed. The patient underwent radical hysterectomy with bilateral pelvic lymph node dissection. The surgical specimen exhibited stromal invasion exceeding 5mm in depth and width greater than 7mm, involving entire cervical wall with lympho-vascular space invasion. The tumor was ER/PR negative, strongly positive for P16, and HPV studies were also positive. Adjuvant external beam radiotherapy (EBRT) was administered to the pelvis, and the patient is currently in remission.

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.

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.

Papiloma escamoso oral, actualización literaria a propósito de un caso / Oral squamous papilloma, literary update regarding a case

En 1871, el cirujano Johann von Mikulicz Radecki, de la Universidad de Viena en Austria, introdujo por primera vez la descripción del papiloma escamoso; finalmente en 2002, se reclasificó como una familia independiente con un total de 29 genes, de los cuales cinco se asocian al papiloma humano. En 2021, el Centro Internacional de Referencia del Virus del Papiloma Humano del Instituto Karolinska reportó un total de 228 diferentes tipos de VPH (AU)

In 1871, the surgeon Johann von Mikulicz Radecki, from the University of Vienna in Austria, first introduced the description of squamous papilloma; finally, in 2002, it was reclassified as an independent family with a total of 29 genes, of which five are associated. to human papilloma. In 2021, the International Reference Center for Human Papillomavirus at the Karolinska Institute reported a total of 228 different types of HPV (AU)

HPV-DNA test access based on self-collection of vaginal samples from women living with HIV/AIDS: pilot implementation in Brazil / Autocoleta vaginal por mulheres vivendo com HIV/AIDS para testagem de HPV-DNA: implantação piloto no Brasil

Introduction: Women living with HIV/AIDS have a higher frequency of anogenital neoplasms resulting from human papillomavirus (HPV) infection. The World Health Organization recommends that cervical cancer screening uses molecular tests that amplify viral genetic material, such as HPV-DNA. In addition to collection by health professionals, self-collection of vaginal samples is a useful tool for expanding access to testing. Objective: To describe the results of the pilot study that evaluated the acceptability of self-collection of vaginal samples and the applicability of offering HPV-DNA tests with self-collection of vaginal samples for women living with HIV/AIDS in Brazil. Methods: Descriptive cross-sectional study involving women living with HIV/AIDS treated in eight HIV-specialty healthcare facilities distributed in all regions of the country from May 2021 to May 2022 and a central laboratory. Vaginal self-collection was offered, and participants were interviewed about sociodemographic data and impressions of self-collection. Results: In total, 1,919 women living with HIV/AIDS with an average age of 45 years participated in the study. Some type of HPV was detected in 66% (1,267) of cases. The majority (71.9%) said they preferred self-collection to sample collection by health care professionals. Only 53.8% of participants underwent cytology at the appropriate frequency, as recommended by the protocol. Conclusion: The results may support the implementation of molecular biology tests to detect HPV in women living with HIV/AIDS, including the possibility of vaginal self-collection, promoting increased access to cervical cancer screening. (AU)

Introdução: Mulheres vivendo com HIV/AIDS possuem maior frequência de neoplasias anogenitais decorrentes da infecção pelo papilomavírus humano (HPV). A Organização Mundial da Saúde recomenda que o rastreio de câncer do colo do útero seja utilizado por testes moleculares que amplificam o material genético viral, como o HPV-DNA. Além da coleta por profissionais da saúde, a autocoleta de amostras vaginais consiste em uma ferramenta útil para ampliação do acesso à testagem. Objetivo: Descrever os resultados do estudo piloto que avaliou a aceitabilidade da autocoleta de amostra vaginal e aplicabilidade da oferta de testes HPV-DNA com autocoleta de amostras vaginais para mulheres vivendo com HIV/AIDS no Brasil. Métodos: Estudo transversal descritivo envolvendo mulheres vivendo com HIV/AIDS atendidas em oito serviços ambulatoriais distribuídos em todas as regiões do país no período de maio/2021 a maio/2022 e um laboratório central. Realizou-se a oferta de autocoleta vaginal e uma entrevista com as participantes sobre dados sociodemográficos e impressões da autocoleta. Resultados: No total, 1.919 mulheres vivendo com HIV/AIDS com média de 45 anos participaram do estudo. Houve detecção de algum tipo de HPV em 66% (1.267) dos casos. A maioria (71,9%) afirmou preferir a autocoleta à coleta de amostras por profissionais da saúde. Apenas 53,8% das participantes realizaram citologia na periodicidade adequada, conforme recomendação do protocolo. Conclusão:Os resultados poderão apoiar a implementação dos testes de biologia molecular para detecção de HPV em mulheres vivendo com HIV/AIDS, incluindo a possibilidade de autocoleta vaginal, promovendo a ampliação do acesso ao rastreamento de câncer do colo do útero. (AU)

Nivel de conocimiento sobre VPH en estudiantes de la Universidad del Pacífico

Introducción. El virus del papiloma humano (VPH) es una infección viral más habitual del aparato reproductor y causa diversos trastornos, tanto en hombres como en mujeres, y se considera como el principal agente para el desarrollo del cáncer cervicouterino. Objetivo. Determinar el nivel de conocimiento sobre el VPH de las alumnas del segundo año de las diferentes carreras de la Universidad del Pacífico Sede Asunción en el año 2023. Materiales y Métodos. Se realizó un estudio observacional, descriptivo de corte transversal en alumnas del segundo año de las diferentes carreras de la Universidad del Pacifico en el 2023, mediante una encuesta de conocimiento, influencia y métodos para evitar el contagio del VPH. Se aplicó la estadística descriptiva utilizando el programa EpiDat 4.2. Resultados. Participaron 95 alumnas, el 49,92% conoce que el VPH es una infección viral, el 87,37% que su síntoma más común son las verrugas genitales, el 91,58% sabe que la infección por VPH afecta a ambos sexos, el 90,53% que se puede transmitir por vía sexual, 71,58% sabe que puede producir cáncer de cuello uterino y el 86,32% conoce que la vacunación es la principal medida de prevención. El 48% de las estudiantes tuvieron un buen nivel de conocimiento global sobre el VPH. Conclusión. El nivel insuficiente de conocimiento sobre VHP refleja la necesidad de realizar fortalecer el programa educativo universitario y campañas educativas con respecto al VPH y el cáncer de cuello uterino.

Introduction. Human papillomavirus (HPV) is the most common viral infection of the reproductive tract, causes various disorders in both men and women, and it is considered to be the main agent for the development of cervical cancer. Objective. To determine the level of knowledge about HPV among students in the second year of the different careers of the Universidad del Pacífico, Asunción, 2023. Materials and Methods. A cross-sectional, observational, descriptive study was carried out with 2nd year students of the different careers of the Universidad del Pacifico in 2023, by means of a survey of knowledge about HPV, influence, and methods to prevent infection. Descriptive statistics using EpiDat 4.2 software were applied. Results. Of the 95 female students surveyed, 49.92% knew that HPV was a viral infection, 87.37% knew that the most common symptom was genital warts, 91.58% knew that HPV disease affects both sexes, 90.53% knew that it can be transmitted sexually, 71.58% knew that it could cause cervical cancer, and 86.32% knew that vaccination was the main prevention measure, 48% of the students have a good global knowledge about HPV. Conclusion. The insufficient level of knowledge about HPV reflects the need to strengthen the university educational program and educational campaigns regarding HPV and cervical cancer.

Prevalencia y características genotípicas de la infección anal por papilomavirus en una cohorte de hombres que tienen sexo con hombres VIH-positivos / Prevalence and genotypic characteristics of anal papillomavirus infection in a cohort of HIV-positive men who have sex with men

RESUMEN Objetivo: Determinar la prevalencia y las características genotípicas de la infección anal por papilomavirus en hombres que tienen sexo con hombres (HSH) VIH-positivos. Materiales y métodos: Es un estudio observacional prospectivo de corte transversal en HSH VIH-positivos del Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, realizado entre setiembre del 2017 y diciembre del 2018. El estudio del papilomavirus se realizó con una técnica de reacción en cadena de polimerasa evaluando 21 genotipos estratificados según el riesgo oncogénico: seis de bajo riesgo y quince de alto riesgo. Resultados: Se evaluaron 214 HSH VIH-positivos. La prevalencia general de la infección anal por papilomavirus fue de 70% (150/214). 86% (129/150) tuvieron genotipos de alto riesgo oncogénico, de ellos 79% (102/129) tuvieron dos o más genotipos de papilomavirus. Los genotipos de alto riesgo oncogénico más frecuentes fueron: VPH-16, 31% (46/150); VPH-52, 22% (33/150); VPH-33, 21% (31/150); VPH-58, 21% (31/150) y VPH-31, 20% (30/150). El VPH-18 alcanzó el 7% (10/150). Los genotipos de bajo riesgo oncogénico más frecuentes fueron: VPH-6, 30% (45/150) y VPH-11, 29% (44/150). Conclusiones: La prevalencia de la infección anal por papilomavirus en HSH VIH-positivos es muy alta en el hospital investigado. La gran mayoría de estas infecciones se producen con genotipos de alto riesgo oncogénico. El papilomavirus 16 fue el genotipo de alto riesgo más frecuente.

ABSTRACT Objective: To determine the prevalence and genotypic characteristics of anal papillomaviruses in HIV-positive men who have sex with men (MSM). Materials and methods: This is a prospective cross-sectional observational study of HIV-positive MSM at Almenara General Hospital between September 2017 and December 2018. HPV detection and typing was performed using a polymerase chain reaction technique that evaluated 21 genotypes stratified according to oncogenic risk into six low-risk and fifteen high-risk. Results: we evaluated 214 HIV-positive MSM. The overall prevalence of anal infection by papillomavirus infection was 70% (150/214). 86% (129/150) were caused by high-risk genotypes, 79% (102/129) of them were affected by a two or more-papillomavirus genotype. The most frequent high-risk genotypes were HPV-16, 31% (46/150); HPV-52, 22% (33/150); HPV-33, 21% (31/150); HPV-58, 21% (31/150) and HPV-31, 20% (30/150). In addition, HPV-18 reached 7% (10/150). The most frequent low-risk genotypes were HPV-6, 30% (45/150) and HPV 11, 29% (44/150). Conclusions: Prevalence of anal papillomavirus infection in HIV-positive MSM is very high in the hospital investigated. Most of these infections occurs with high-risk oncogenic genotypes. Papillomavirus 16 was the most frequent high-risk genotype.

Research progress on diabetes and human papilloma virus infection and vaccination / 公共卫生与预防医学

Diabetes is a common chronic non-infectious disease. Diabetic patients not only suffer from metabolic disorders, but are also prone to immune deficiencies and are at a higher risk of being infected with human papillomavirus (HPV). Many studies at home and abroad have shown that the HPV infection rate of patients with diabetes is higher than that of non-diabetic patients. Patients with diabetes can benefit from HPV vaccination, and the tolerance is good. HPV vaccination is recommended for diabetic patients. This article reviews the research on diabetes, HPV infection, and HPV vaccine, which will provide references for HPV vaccination in diabetic patients.

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.

Expression and significance of cyclin dependent kinase inhibitor 3 in HPV16-positive cervical cancer / 重庆医学

Objective To investigate the expression and significance of cyclin dependent kinase inhibitor 3(CDKN3)in human papillomavirus type 16(HPV16)-positive cervical cancer.Methods CDKN3 expression in pan-cancer was retrieved and downloaded from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,and the expression levels of CDKN3 between normal cervical tissues(13 samples)and cervical cancer tissues(306 samples)were compared.Subsequently,GSE39001 data of HPV16-positive cervical cancer was sourced and downloaded from the Gene Expression Omnibus(GEO)database,and the expression levels of CDKN3 mRNA in HPV16-positive cervical cancer tissues(43 samples)and normal cervical tissues(12 samples)were compared.Immunohistochemical method was used to detect the expression of CDKN3 in 12 ca-ses of HPV16-positive cervical cancer,12 cases of HPV16-positive cervical precancerous lesions,10 cases of HPV16-positive chronic cervicitis and 7 cases of HPV-negative normal cervical samples collected from the Af-filiated Hospital of Guizhou Medical University.SiHa(HPV16-positive),HeLa(HPV18-positive)and HCC94(HPV-negative)cervical cancer cell lines were selected,and their CDKN3 expression were detected by West-ern blot.Results The GEPIA platform analysis showed that CDKN3 was highly expressed in pan-cancer,and the expression level of CDKN3 in cervical cancer tissue was significantly higher than that in normal cervical tissue(P<0.05).The GEO dataset reflected a significantly increased CDKN3 mRNA expression level in HPV16-positive cervical cancer compared to normal cervical tissue(P<0.001).Immunohistochemical verifi-cation showed that the positive expression rates of CDKN3 in HPV16-positive cervical cancer,HPV16-positive cervical precancerous lesion,HPV16-positive chronic cervicitis and HPV-negative normal cervical tissues were 91.7%,58.3%,0 and 0,respectively.Western blot analysis of cervical cancer cells showed that the expression level of CDKN3 in SiHa(HPV16-positive)cells was significantly higher than that in HeLa(HPV18-positive)and HCC94(HPV-negative)cells(P<0.05).Conclusion CDKN3 is a new oncogene of HPV16-positive cer-vical cancer,which may be used as a marker of cervical precancerous lesions and cervical cancer screening,and may provide a theoretical basis for subsequent mechanism research and targeted therapy.

Expression of serum lncRNA CCDC18-AS1 and miR-501 in patients with HPV-infected cervical cancer and its correlation with prognosis / 国际检验医学杂志

Objective To explore the expression of serum long noncoding RNA(lncRNA)CCDC18-AS1 and microRNA-501(miR-501)in patients with human papillomavirus(HPV)-infected cervical cancer,and its correlation with prognosis.Methods A total of 78 patients with HPV-infected cervical cancer who underwent treatment in the hospital from May 2019 to May 2020 were enrolled as study group,meantime,80 patients with simple HPV infection and 81 patients with simple non-HPV infected cervical cancer were set as control group 1 and control group 2.Serum lncRNA CCDC18-AS1 and miR-501 expression levels were detected by re-al-time quantitative PCR.Then the clinical features,postoperative overall survival and progression-free surviv-al were analyzed in the study group.Results The relative expression levels of serum lncRNA CCDC18-AS1 and miR-501 in the study group were higher than those in control group 1 and control group 2(P<0.05),and the relative expression levels of serum lncRNA CCDC18-AS1 and miR-501 in control group 2 were higher than those in control group 1(P<0.05).Pearson correlation analysis showed that serum lncRNA CCDC18-AS1 and miR-501 were positively correlated in the study group(r=0.421,P<0.001).Serum lncRNA CCDC18-AS1 and miR-501 in study group were not related to age,but were related to clinical stage,differentiation de-gree,lymph node metastasis,and squamous epithelial cell antigen(P<0.05).Kaplan Meier analysis showed that the postoperative overall survival and progression-free survival of high lncRNA CCDC18-AS1 and miR-501 expression groups were shorter than those of low expression groups(P<0.05).Conclusion HPV-infec-ted cervical cancer patients have up-regulated expression of serum lncRNA CCDC18-AS1 and miR-501,and the abnormal changes are closely related to patients'clinical characteristics and postoperative survival,so the two indicators could be used as auxiliary indicators for the disease assessment and prognosis evaluation.

The value of HPV DNA and HPV E6/E7 mRNA detection in screening for cervical lesions / 国际检验医学杂志

Objective To investigate the value of human papillomavirus(HPV)DNA and HPV E6/E7 mRNA detection in screening for cervical lesions.Methods A total of 619 patients who were screened for cer-vical lesions in West China Second University Hospital from September 2021 to August 2022 were selected as the study objects.The value of HPV DNA and HPV E6/E7 mRNA detection in cervical lesion screening was evaluated based on their pathological results.Results The positive rate of HPV DNA detection was 64.78％(401/619)and that of HPV E6/E7 mRNA detection was 60.74％(376/619)in 619 patients.Cervical lesion screening was mainly conducted in sexually active people aged 30-＜40 years and 40-＜50 years.The posi-tive rates of HPV DNA and HPV E6/E7 mRNA increased with the increase of cervical lesion grade.The sen-sitivity,positive predictive value and negative predictive value of the two methods were higher than those of HPV DNA or HPV E6/E7 mRNA detection.Conclusion The combined detection of the two methods can be used for screening cervical lesions at various pathological stages,which can provide greater guidance value in clinical diagnosis and treatment.

Analysis of HPV infection and genotype distribution among 1 658 male reproductive health outpatients / 复旦学报（医学版）

Objective To investigate the human papillomavirus(HPV)infection and genotype distribution characteristics among male reproductive health outpatients,and to compare the differences among different age groups of outpatients.Methods A total of 1 658 males,visited in the Affiliated Hospital of Shanghai Institute of Planned Parenthood Research from 2018 to 2022,were selected and 23 HPV genotypes were detected by PCR-reverse dot hybridization.Results Among the 1 658 subjects,the overall HPV infection rate was 22.50%.Single infection accounted for 66.76%,which was the main infection type.HPV infection among different age groups were statistically significant(P<0.001),with HPV infection of 16.83%,22.87%,34.63%,and 29.35%for 18-30,31-40,41-50,and≥51 years,respectively.The top 5 high risk HPV genotypes were HPV52(3.56%),HPV16(3.26%),HPV39(2.41%),HPV51(2.17%),HPV58(2.17%),and the top 1 low risk HPV genotype was HPV81(2.90%).The proportions of infected individuals in this study that could be completely covered by bivalent,quadrivalent,and nine-valent HPV vaccines were 7.77%,12.33%,and 26.27%,respectively.Conclusion The predominant infection type among male reproductive health outpatients was single infection type.HPV 52,16,39,51 and 58 were the most common high risk genotypes,while HPV 81 was the most common low risk genotype.Individuals aged 41-50 years had the highest HPV infection rate.

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.

Analysis of External Quality Assessment Results for HPV6 and HPV11 Nucleic Acid Testing in Clinical Laboratories of Shanghai and Other Provinces and Cities from 2020 to 2022 / 现代检验医学杂志

Objective To evaluate the testing capabilities of laboratories,analyze existing issues,and improve testing quality,through carrying out the external quality assessment(EQA)of clinical laboratories for human papillomavirus(HPV)type 6 and 11 nucleic acid detection.Methods EQA plan was carried out twice a year.Each panel contains 4 positive samples,including one strong positive sample and one weak positive sample of HPV6 and HPV11,made from cervical secretions from patients with clinical manifestations of condyloma acuminata(CA)and positive for HPV6 or HPV11(from Shanghai First Maternity and Infant Hospital).One negative sample was cultured from the C-33A cell line(from Chinese Academy of Sciences).Samples were sent to participating laboratories by cold chain,and laboratories were required to detect test samples and upload their results within the specified time.Shanghai Center for Clinical Laboratory(SCCL)calculated the scores of each laboratory based on the return results.Results A total of 163 sample panels were sent out in the 6 rounds of EQA plan and 140 valid reports were received.The laboratory qualification rate was 96.43%(135/140)and the sample compliance rate was 97.86%(685/700).There were 13 false negative results and 2 false positive results,with weakly positive samples accounting for 76.92%(10/13)of the false negative results.Conclusion The detection accuracy of HPV6/11 nucleic acid in each laboratory was relatively high,and the detection ability of weak positive samples in individual laboratories may need to be improved.The laboratory could discover problems and improve its quality management by participating in EQA.

Evaluation of the Impact of Human Papillomavirus Infection on the Clinical Outcomes of Intra-Uterine Insemination in Infertile Women Based on Propensi-ty Score Matching Method / 实用妇产科杂志

Objective:To evaluate the impact of human papillomavirus(HPV)infection on the clinical outcomes of intrauterine insemination(IUI)in infertile women.Methods:The clinical data of 685 patients(1046 cycles)who underwent IUI treatment were retrospectively analyzed at Tangdu Hospital of Air Force Medical University from January 2019 to July 2021,including 554 cases of artificial insemination with husband sperm(AIH).According to HPV infection,patients were divided into two groups,HPV positive group and HPV negative group,propensity score matching(PSM,1 ∶ 2)was used for IUI(80 cases in HPV-positive group and 158 cases in HPV-negative group)and AIH(65 cases in HPV-positive group and 129 cases in HPV-negative group)treatment patients,and the clinical outcomes of these patients were compared respectively.Results:There was no statistically significant difference in clinical pregnancy rate,live birth rate,ectopic pregnancy rate,abortion rate,macrosomia birth rate,and low body weight birth rate between HPV-positive group and HPV-negative group after matching with IUI treat-ment patients(P>0.05).There was no statistically significant difference in clinical pregnancy rate,live birth rate,ectopic pregnancy rate,miscarriage rate,macrosomia birth rate,and low body weight birth rate between the HPV positive group and the HPV negative group after matching AIH treatment patients(P>0.05).Conclusions:HPV infection in infertile female may not affect the clinical outcomes of IUI patients.

HPV16 E6 regulates miR-23a expression and promotes invasion and migration of cervical cancer cells / 实用医学杂志

Objective To investigate the effects of high-risk human papillomavirus 16 E6 protein(HPV16 E6 protein)on invasion and migration of cervical cancer SiHa cells via regulating the expression of expression miR-23a.Methods Tissue samples from 100 patients with cervical cancer HPV-negative,100 HPV-positive patients,and 100 paracancerous normal tissues were collected;cervical cancer SiHa cells were divided into blank group,E6 overexpression group,negative transfection group,and E6 + miR-23a mimics group.The expression of miR-23a and HPV16 E6 mRNA were detected by qRT-PCR;MTT assay was used to detect the cell proliferation inhibition rate;flow cytometry to detect the apoptosis;Transwell chamber assay to detect cell invasion,and scratch test to detect the ability of cell migration.The expression of HPV16 E6,apoptosis related proteins(Caspase-3,Bax,Bcl-2),and migration related proteins(MMP-2,MMP-9)was detected by WB.Results The expression level of miR-23a was decreased in cervical cancer tissues,and that was lower in HPV positive cervical cancer tissues.Overexpression of E6 decreased the expression level of miR-23a,cell proliferation inhibition rate,apoptosis rate,Caspase-3 and Bax protein expression,and increased the expression of Bcl-2 protein,scratch healing rate,inva-sion cell number,MMP-2,MMP-9 protein expression(P<0.05);miR-23a mimics reversed the effects of E6 overexpression on the above indicators.Conclusion HPV16 E6 promotes the invasion and migration of cervical cancer cells,which may be related to the regulation of miR-23a expression.

Development of a typing detection method for high-risk human papillomavirus and related tumor suppressor genes p53 and RB1 based on two-dimensional PCR technology / 中华检验医学杂志

Objective:To establish a single-tube, one-step method for detecting and identifying 16 high-risk human papillomavirus (HR-HPV) subtypes (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, 82) and genotyping p53 (rs1042522) and RB1 (rs3092905) in cervical cells, using high-throughput two-dimensional PCR (2D-PCR) technology. Methods:Applied Research. Specific primers were designed according to the DNA sequences of the 16 different HR-HPV subtypes, p53, and RB1 genes, with the target genes p53 and RB1 serving as internal references to assess the success of sample collection and PCR amplification. In three fluorescent detection channels, upstream primers labeled with corresponding tags were used for different HR-HPV subtypes, p53, and RB1, constructing a comprehensive 2D-PCR detection system. Using this method, 804 cervical brush samples collected from the gynecology outpatient department of Changzhou First People′s Hospital from December 2022 to August 2023 were tested. The test results were compared for consistency with PCR-reverse dot blot assay, flow cytometric fluorescence hybridization assay, and single-plex real-time quantitative PCR assay, respectively. Meanwhile, the genotypes of p53 and RB1 were detected using Sanger sequencing. The Kappa test was applied to determine the consistency between 2D-PCR method and other methods. Results:2D-PCR accurately discriminated and identified the genotypes of 16 HR-HPV types and p53, RB1 through characteristic melting valleys in the FAM, HEX, and Alexa Fluor568 channels. 2D-PCR showed high consistency with PCR-reverse dot blot assay, with a Kappa value of 0.699, even higher consistency with flow cytometric fluorescence hybridization assay, with a Kappa value of 0.793, and the highest consistency with single-plex quantitative PCR, with a Kappa value of 0.880 (95% CI 0.862-0.907). Using Sanger sequencing as the gold standard, the accuracy of 2D-PCR method in detecting p53 and RB1 genotypes is 100%. The distribution frequencies of the three genotypes (G/G, G/C, and C/C) at the p53 rs1042522 locus were 32.09% (258/804), 49.88% (401/804) and 18.03% (145/804), respectively, while all detected genotypes at the RB1 rs3092905 locus were A/A. Conclusion:This study successfully developed a 2D-PCR method for the identification and genotyping of high-risk human papillomavirus types and related tumor suppressor genes p53 and RB1 for cervical cancer.

Report of two cases of urticaria vasculitis after vaccination / 上海预防医学

Vaccination is the most economical and effective measure to prevent infectious diseases targeted by vaccines. Despite this， the safety of vaccines has garnered increased attention due to recent vaccine incidents. The tetravalent human papillomavirus vaccine （HPV） is one of the effective means to prevent cervical cancer and in situ adenocarcinoma caused by infection with corresponding serotypes. The inactivated novel coronavirus vaccine is an emergency vaccine developed to prevent novel coronavirus infection after the COVID-19 outbreak， and is also the main measure used to control the spread of COVID-19 at present. The monitoring data show that both vaccines have good safety after inoculation， but due to individual differences and other reasons， rare reactions may occur in a very small number of recipients. This article presents two cases of urticaria vasculitis following inoculation of the tetravalent HPV and the novel corona virus inactivated vaccine.