Observation on the composition and distribution of human papillomavirus infection and its aging changes in female genital tract of Zhuang and Han nationality in Guangxi / 中华老年医学杂志

Objective:To study the composition and distribution of human papillomavirus(HPV)in female genital tract of Zhuang and Han nationality in Guangxi.Methods:The composition and distribution of cervical human papillomavirus(HPV)infection in Han and Zhuang women visiting Department of Gynecology and Obstetrics of the First Affiliated Hospital of Guangxi Medical University from August 2012 to October 2020 were retrospectively analyzed to provide the basic data for prevention and treatment of HPV infection.A total of 20 736 cases were divided into Han nationality group(n=16 390 cases)and Zhuang nationality group(n=4 346 cases). Polymerase chain reaction(PCR)was used to detect HPV type 21 and analyze the epidemiological characteristics of cervical HPV in women of different ethnic groups in this area.Results:In the 20, 736 cases, the proportion of positive HPV was 27.0%(5 591/20, 736). Among them, positive HPV accounted for 27.7%(4 536)in the Han group, and 24.3%(1 055)in Zhuang group, which were statistically significant( χ2=20.17, P<0.01). Peak age of infection in Zhuang women was more than 65 years.The most common HPV genotypes in both ethnics groups in Guangxi were HPV 16, 52, 58, 18, and 53.In women with positive HPV, the constituent ratio of HPV16 and HPV 52 rose with age ageing, while constituent ratio of HPV 6 and 11 presented the opposite trend. Conclusions:The HPV and HR(high-risk)-HPV positive composition ratio is lower in Zhuang women than in Han women in Guangxi.Among Han and Zhuang females, HPV 16, 52, 58, 18 and 53 have the highest positive composition ratio.HPV genotyping shows an age-increasing change.

Frequency of high-risk genotypes of human papilloma virus in oral lesions / Frecuencia de genotipos alto riesgo del virus papiloma humano en lesiones bucales

Some genotypes of the human papilloma virus (HPV) in the oral cavity cause genetic instability that may lead to cancer. Clinical and histological diagnoses are key tools; however, molecular techniques allow predicting, detecting and monitoring the disease. Objective: To identify the frequency of four high-risk HPV genotypes and their association with lesions in the oral cavity. Materials and Methods: Descriptive cross-sectional study with a sample of 48 patients diagnosed with hyperplastic lesions and others currently classified as potentially malignant disorders (PMDs) of the oral cavity, who underwent biopsies, histopathological analysis, and HPV16, 18, 31, and 45 detection and genotyping by polymerase chain reaction (PCR). Results: Epithelial hyperplasia was the most frequent lesion found in 45.8% (n=22) of patients. Nicotine palatinus and leukoplakia were found in 8.3% and 6.2%, respectively; oral cancer in 6.2%. The total frequency of HPV was 12.5% (6/48). Oral papilloma was found in 6.1% (3/48), and nicotine palatinus and oral cancer in 2.0% each (1/48). HPV16, HPV31, and HPV45 were detected, while HPV18 was not observed. HPV16 was the most frequent genotype found (4 out of 6 patients), while HPV31 and HPV45 were found in one patient each. Only one genotype per lesion was found. The presence of HPV was associated with lesions (χ2=11.810; p=0.0375). No significant association with age and gender was found. Conclusion: High-risk HPV continues to be present in oral lesions. The HPV16 viral genotype was the most frequent in the studied lesions.

Algunos genotipos del virus del papiloma (VPH) en boca, producen inestabilidad genética dando lugar al cáncer. El diagnóstico clínico e histológico son herramientas claves, sin embargo, técnicas moleculares permiten predecir, detectar y dar seguimiento a la enfermedad. Objetivo: Identificar la frecuencia de cuatro genotipos del VPH de alto riesgo y su asociación con lesiones en cavidad bucal. Material y Métodos: Estudio descriptivo de corte transversal con una muestra de 48 pacientes diagnosticados con lesiones hiperplásicas y otros clasificados actualmente como desordenes potencialmente malignos (DPM) de la cavidad bucal, a quienes se les realizó biopsias, análisis histopatológico y detección y genotipificación VPH16, 18, 31, y 45 mediante reacción en cadena a la polimerasa (PCR). Resultado: La hiperplasia epitelial fue la lesión más frecuente en 45,8% (n=22). La palatinitis nicotínica y la leucoplasia, se encontraron 8,3% y 6,2% respectivamente, cáncer oral, en 6,2%. La frecuencia total de VPH fue 12,5% (6/48). El papiloma oral estuvo en un 6,1% (3/48), palatinitis nicotínica y cáncer oral en 2,0% (1/48).Se detectó VPH16, VPH31 y VPH45, mientras que VPH18 estuvo ausente. ElVPH16 fue el de mayor frecuencia con 66,7% (4/6), el VPH31 y VPH45 se encontraron en 16,7% (1/6). No se evidenció más de un genotipo por lesión. La presencia de VPH estuvo asociado con las lesiones (χ2=11,810; p=0,0375). No se encontró asociación significativa con edad y género. Conclusión: El VPH de alto riesgo sigue estando presente en lesiones bucales. El genotipo viral VPH16 se encontró con mayor frecuencia en las lesiones estudiadas.

Clinical significance of human papillomavirus 16/18 E6 protein detection in shunting and prognosis of patients with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions / 肿瘤研究与临床

Objective To evaluate the value of human papillomavirus (HPV) 16/18 E6 protein detection in shunting and prognosis in patients with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL). Methods A total of 98 patients with ASCUS or LSIL from the Affiliated Cancer Hospital of Shanxi Medical University between May 2014 and May 2015 were selected as the subjects. All of them received the thin-cytologic test (TCT), HPV DNA, HPV16/18 E6 protein tests and colposcopy examination. After 3-year follow-up of patients with cervical intraepithelial neoplasia (CIN) grade Ⅰor bellow lesions diagnosed by biopsy and 30 negative controls, the above tests were performed again. The efficacies of all the tests were analyzed. The value of CIN grade Ⅱ or above was predicted. Results The sensitivity, specificity, positive predictive value and negative predictive value in predicting CIN grade Ⅱor above lesions of HPV16/18 E6 protein , HPV DNA and HPV16/18 DNA was 30.8％, 95.3％, 50.0％, 90.0％, respectively; 84.6％, 37.6％, 17.2％, 94.1％, respectively and 61.5％, 67.1％, 22.2％, 91.9％, respectively in shunting study. The relative risk (RR) of CIN grade Ⅱor above lesions in patients with positive HPV16/18 E6 protein, persistent positive HPV16/18 DNA and positive HPV16/18 DNA was 13.429, 10.231 and 8.343, respectively in the follow-up study. Odds ratio (OR) of HPV16/18 E6 positive protein presenting persistent positive HPV16/18 DNA was 34.833 (95％ CI 5.020-241.711). Conclusions In patients with ASCUS and LSIL, the specificity and positive predictive value of HPV16/18 E6 protein in predicting CIN grade Ⅱ or above lesions are higher than those of HPV DNA and HPV16/18 DNA. Moreover, these patients with HPV16/18 E6 protein positive have a higher risk of developing CIN grade Ⅱ or above lesions and persistent positive HPV16/18 DNA.

HPV E6 and E7 mRNA combined with HPV 16 and 18 or 45 genotyping testing as a means of cervical cancer opportunistic screening / 中华妇产科杂志

Objective To evaluate Aptima HPV E6 and E7 mRNA assay (Aptima HPV) combined with Aptima HPV 16 and 18 or 45 (18/45) genotype assay (Aptima HPV-GT) as a means of cervical cancer opportunistic screening. Methods From October 2016 to October 2017, a total of 23 258 women aged 25-65 years were enrolled in the physical examination center and gynecological clinic of Huzhou Maternity and Child Health Care Hospital. All the women had Aptima HPV tested, further Aptima HPV-GT testing for positive women and liquid-based thin layer cytology Thinprep cytologic test (TCT). Women with Aptima HPV (+) or ≥low-grade squamous intraepithelial lesion (LSIL) or obvious clinical symptoms (including vaginal bleeding after intercourse and watery, bloody vaginal discharge) were referred for colposcopy and further biopsy with or without endocervical curettage (ECC) if indicated. Expression of Aptima HPV, HPV 16 and HPV 18/45 with different cytological diagnostic groups and histological diagnosis groups were compared respectively. Sensitivity, specificity, positive predictive value and negative predictive value of Aptima HPV detection and TCT in identifying histological diagnosis of high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL+) were compared. Results (1) The positive rates of Aptima HPV, HPV 16 and HPV 18/45 were 14.00% (3 257/23 258), 1.85% (430/23 258) and 0.86% (199/23 258) respectively.The positive rates of Aptima HPV, HPV 16 and HPV 18/45 increased with cytology grading in squamous epithelium [negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASCUS), LSIL, atypical squamous cell cannot exclude HSIL (ASC-H), HSIL and squamous cell carcinoma (SCC), all P=0.000)]. According to histology results, the positive rates of Aptima HPV, HPV 16 and HPV 18/45 increased with histology grading in squamous epithelium (normal cervical tissue, LSIL, HSIL and SCC, all P=0.000). The positive rate of Aptima HPV was significantly higher in HSIL+group than that in the LSIL or better (LSIL-) group [98.11% (311/317) vs 12.84% (2 946/22 941), P=0.000]. The positive rate of Aptima HPV-GT was significantly higher in HSIL+group than that in LSIL-group [58.36% (185/317) vs 1.91% (439/22 941), P=0.000]. (2) Compared with cytology, Aptima HPV resulted in significant higher sensitivity (98.11% vs 59.62%, P=0.000) and negative predictive value (99.97% vs 99.42%, P=0.000), significant lower specificity (87.16% vs 95.37%, P=0.000) and positive predictive value (9.55% vs 15.10%, P=0.000) when identified HSIL+. Conclusions Women with Aptima HPV positive, especially those with Aptima HPV-GT positive, are more likely to have histological diagnosis of HSIL+. Aptima HPV combined with Aptima HPV-GT is feasible as a means of cervical cancer opportunistic screening in tertiary hospitals.

Prevalence of high-risk HPV and its distribution in cervical precancerous lesions among 35-64 years old women who received cervical cancer screening in Beijing / 中华预防医学杂志

Objective@#To study the prevalence of high-risk HPV (HR HPV) in women who accepted cervical cancer screening in Beijing and its distribution in cervical precancerous lesions.@*Methods@#From January 2014 to March 2015, all women aged 35-64 years old and received free screening in institutions of cervical cancer in Beijing were recruited. Stratified cluster random sampling method was used in selecting 31 091 women for gynecological examination and genotyping of HR-HPV. Those positive for HR-HPV (except for HPV 16/18) were examined for cervical cell. For those atypical squamous cells of uncertain significance (ASCUS) and above, who were positive for HPV 16/18 and with uncertain results for cervical cell, were transferred for colposcopy examination. For those with suspicious or abnormal results for colposcopy, were transferred for histopathology. The prevalence of HR-HPV, cervical cancer and precancerous lesions among the participants were analyzed.@*Results@#Totally 31 091 women aged from 35-year-old to 64-year-old, with 44.3% (13 780 women) in the 35-49 age group and 55.7% (17 311 women) in the 50-64 age group. 66.1% (20 536 women) were rural women. The infection rate of HR-HPV was 7.4%(2 305 cases) among the women. High-risk infection rates of HPV except HPV 16/18 were 5.7% (1 758 cases), and multi-infection rate was 1.5% (477 cases). The highest infection rate was 7.9% (1 044 cases) among the 45-49 year-old and 50-54 year-old age groups (χ2=14.07, P=0.015). The rate in rural women was significantly higher than that of the urban women (6.2%, 507 cases; 7.9%, 1 798 cases) (χ2=25.75, P<0.001). The proportion of HPV16, HPV18, HPV52, HPV51, HPV58 was 17.0% (391 cases), 6.9% (161 cases), 8.6% (20 cases), 5.2% (12 cases) and 7.7% (18 cases), respectively. The detection rate of cervical cancer and precancerous lesions in the population was 395.6/100 000 (123 cases). In high-grade squamous intraepithelial lesions (HSIL), HPV16 and 18 infections accounted for 60.5% (72 cases) of all. HPV16 infection rate and detection rate of HSIL were the highest in 50-54 year-old group which were 1.5% (107 cases) and 25.2% (30 cases) (χ2=11.54, P=0.042).@*Conclusion@#Top five types of HR-HPV infection in women who accepted cervical cancer screening in Beijing were HPV16, 18, 52, 51 and 58. The infection rate of HPV16 and 18 increased significantly in HSIL women. HPV16 infection rate and detection rate of HSIL were the highest in 50-54 year-old age group.

Distribution and associated factors of high-risk HPV genotypes infection among HPV-positive women who participated cervical screening test in Shenzhen, 2014-2016, China / 中华预防医学杂志

Objective@#To analyze the distribution and associated factors of high-risk genotypes of HPV in cervical infection among women in Shenzhen.@*Methods@#The information on sociodemographic characteristics and HPV genotypes of HPV-positive women who participated cervical screening test from January 2014 to December 2016 was downloaded from Shenzhen Maternity and Child Healthcare Management Information System. According to the pathogenicity, the high-risk HPV genotypes were divided into 15 types including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68; and there were 6 low-risk genotypes including HPV 6, 11, 42, 43, 44, and 81. Chi-square tests were applied to compare the proportions of high-risk HPV infection among women who had different sociodemographic characteristics. A non-conditional logistic regression model was used to analyze the associated factors for high-risk HPV infection.@*Results@#In total, all HIV positives received HPV genotyping, with an average age of (38.08±9.38) years old. There were 9 979 (93.9%) high-risk and 645 (6.1%) low-risk HPV infections. The proportions of HPV infections for high-risk type in each year were 91.5%, 93.8%, and 95.6%, increasing with the screening years (χ2=54.79, P<0.001). Multivariate logistic regression analysis showed that compared with women younger than 25 years old, women in other age groups (at age 26 to 30 years, 31 to 35 years, 36 to 40 years, 41 to 45 years, and 50 years or older) had increased risks of high-risk HPV infection, with OR (95%CI) of 1.67 (1.20-2.31), 1.49 (1.09-2.03), 1.71 (1.23-2.37), 1.65 (1.19-2.31), and 1.84 (1.26-2.67), respectively; compared with the married, single women had a decreased risk of high-risk HPV infection (OR (95%CI): 0.71 (0.50-1.00)); women received HPV testing in 2015 and 2016 showed higher risk of high-risk HPV infection than those in 2014 (OR (95%CI): 1.43 (1.17-1.74) and 2.03 (1.68-2.46)). The 5 most common HPV genotypes were HPV52 (25.1%, 2 670 cases), followed by HPV16 (19.2%, 2 041 cases), HPV58 (13.3%, 1 413 cases), HPV18 (9.9%, 1 048 cases), and HPV51 (9.3%, 993 cases).@*Conclusion@#Age, marital status, and screening year were associated with high-risk HPV infections. Besides HPV16 and HPV18, the prevention and control on HPV infections for HPV52, HPV58, and HPV51 should be prioritized in Shenzhen area.

Pigmented Bowen's disease associated with high-risk HPV simulating melanoma of the hand

Abstract: Bowen's disease is an in situ squamous cell carcinoma of the skin with only 2% of pigmented cases reported. It is clinically characterized by papules and plaques of blackened surface that may be caused either by sun damage - usually in photoexposed areas in elderly individuals - or by human papillomavirus infection - usually in the anogenital region of young adults. Dermoscopic aspects of Bowen's disease are discussed for over a decade, but with no definitive criteria that would lead to a definitive diagnosis. We present a case of Bowen's disease affecting the finger of a 57-year-old Asian patient. The lesion clinically and dermoscopically simulated a melanoma. Histopathological findings suggested the diagnosis of pigmented Bowen's disease. Pigmented Bowen's disease should be considered a differential diagnosis of melanoma, since its clinical and dermoscopic criteria are unspecific. Histopathological examination remains the gold standard for the diagnosis of the disease.

Prevalence of Human Papillomavirus Infection and Cervical Cancer Screening among Riverside Women of the Brazilian Amazon / Prevalência da infecção pelo papilomavírus humano e rastreamento do câncer em mulheres ribeirinhas da Amazônia brasileira

Abstract Purpose The aim of this study was to evaluate the overall and type-specific prevalence of human papillomavirus (HPV) infection among females living in riverside communities in the state of Pará, in the Eastern Brazilian Amazon. These communities are inhabited by low-income people, and are accessible only by small boats. Cervical cytology and risk factors for HPV infection were also assessed. Methods Cervical samples from 353 women of selected communities were collected both for Papanicolau (Pap) test and HPV detection. Conventional polymerase chain reaction (PCR) and real-time PCR were used to assess the overall and type-specific prevalence of HPV-16 and HPV-18, the main oncogenic types worldwide. Epidemiological questionnaires were used for the assessment of the risk factors for HPV infection. Results The mean age of the participants was 37 years (standard deviation [SD] ± 13.7). Most were married or with a fixed sexual partner (79%), and had a low educational level (80%) and family monthly income (< U$ 250; 53%). Overall, HPV prevalence was 16.4% (n = 58), with 8 cases of HPV-16 (2.3%) and 5 of HPV-18 (1.4%). Almost 70% of the women surveyed had never undergone the Pap test. Abnormal cytology results were found in 27.5% (n = 97) of the samples, with higher rates of HPV infection according to the severity of the lesions (p = 0.026). Conclusions The infections by HPV-16 and HPV-18 were not predominant in our study, despite the high prevalence of overall HPV infection. Nevertheless, the oncogenic potential of these types and the low coverage of the Pap test among women from riverside communities demonstrate a potential risk for the development of cervical lesions and their progression to cervical cancer, since the access to these communities is difficult and, in most cases, these women do not have access to primary care and public health services.

Resumo Objetivo O objetivo deste estudo foi avaliar a prevalência global e tipo-específica da infecção pelo papilomavírus humano (HPV) entre mulheres que vivem em comunidades ribeirinhas do estado do Pará, Amazônia oriental, Brasil. Estas comunidades são habitadas por pessoas de baixa renda, e são acessíveis somente por meio de pequenos barcos. A citologia cervical e os fatores de risco para a infecção por HPV também foram avaliados. Métodos Amostras cervicais de 353 mulheres de comunidades selecionadas foram coletadas para a análise citológica e para a detecção do HPV. A prevalência global e tipoespecífica dos HPV-16 e HPV-18, principais tipos oncogênicos no mundo, foram avaliadas por meio de reação em cadeia de polimerase (PCR) convencional e PCR em tempo real. Os fatores de risco para a infecção por HPV foram avaliados a partir de questionários epidemiológicos. Resultados A idade média das participantes foi de 37 anos (desvio padrão [DP] ± 13,7). A maioria era casada ou tinha um parceiro sexual fixo (79%) e baixo nível de escolaridade (80%) e de renda familiar mensal (< U$ 250; 53%). A prevalência global do HPV foi de 16,4% (n = 58), com 8 casos de HPV-16 (2,3%) e 5 casos de HPV-18 (1,4%). Aproximadamente 70% das mulheres entrevistadas nunca tinha realizado o exame preventivo de Papanicolau. Os resultados citológicos anormais foram encontrados em 27,5% (n = 97) das amostras, com taxas mais altas da infecção por HPV de acordo com a severidade das lesões (p = 0,026). Conclusões As infecções por HPV-16 e HPV-18 não foram predominantes em nosso estudo, apesar da alta prevalência global da infecção por HPV. No entanto, o potencial oncogênico desses tipos e a baixa cobertura do exame de Papanicolau entre mulheres de comunidades ribeirinhas demonstram um risco potencial para o desenvolvimento de lesões cervicais e sua progressão para o câncer de colo do útero, uma vez que o acesso a essas comunidades é difícil e, na maioria dos casos, estas mulheres não têm acesso aos serviços de atenção primária e de saúde pública.

To analyse the histopathological results of patients with HPV16/18 positive and colposcopic suspicious lesions / 中华妇产科杂志

Objective To explore the value of histopathologic diagnosis after colposcopy for high-risk HPV16/18 positive patients with negative cytology or atypical squamous cells of undetermined significance (ASCUS) for early screening of cervical lesions. Methods A retrospective study of cervical histopathologic diagnosis in the HPV16/18 positive patients received colposcopy evaluation before got the histology was carried out between January 2014 and January 2016. The cytology of the patients should be negative or ASCUS. A total of 337 patients with age from 21 to 65 years old were enrolled, including 214 patients with negative cytology, and 123 patients with ASCUS. Results (1) The results of pathology were as follows: 63 (18.7%) cases inflammation, 89 (26.4%) cases cervical intraepithelial neoplasia (CIN)Ⅰ, 182 (54.0%) cases CINⅡ-Ⅲ and adenocarcinoma in situ (AIS), and 3 (0.9%) cases minimal invasive cancer (stage Ⅰa1). The incidence of CIN Ⅱ and above cervical lesions was higher in the patients with ASCUS (71.5%, 88/123) than that in the patients with negative cytology (45.3%, 97/214; χ2=24.876, P<0.01),and it was higher in the patients with HPV16 positive (64.4% , 150/233) than that in the patients with HPV18 positive (30.3% , 27/89; χ2=31.388, P<0.01). There was statistically significant difference among the different age group in which the patients of 20- 29 years old was 69.3% (52/75), 30- 39 years old was 55.1% (75/136), 40-49 years old was 44.8% (30/67) and 50 years old and above was 47.5% (28/59; χ2=16.512, P=0.032). (2) Among the patients with negative cytology, the incidence of CINⅡ and above cervical lesions in the patients with HPV16 positive was higher than that in the patients with HPV18 positive [54.8%(80/146)vs 26.0%(20/77);χ2=16.930, P<0.01]. The incidence was also higher in the patients with HPV16 positive than that in the patients with HPV18 positive [76.5%(78/102)vs 55.6%(15/27);χ2=4.642, P=0.031] among the patients with ASCUS. (3) Compared to the patients diagnosed inflammation or CINⅠ, the patients diagnosed CINⅡ and above cervical lesions had higher infection rate of HPV16, lower infection rate of HPV18, higher incidence of ASCUS, and smaller parities (all P<0.05). A multifactor analysis was carried out, the results showed that HPV16 positive and ASCUS might be independent risk factors to predict the incidence of CIN Ⅱ and above cervical lesions(P<0.01). Conclusions The incidence of cervical precancerous lesions is high in the women with HPV16/18 infection. Patients with HPV16 infection are more likely to have the CIN Ⅱ and above cervical lesions than patients with HPV18 infection. Patients with HPV16/18 infection are suggested to be directly transferred to clinic of colposcopy, and then getting the histology selectively, which would be help to early detection of the cervical precancerous lesions.

Subtype distribution analysis of human papillomavirus in women in Jinhua People's Hospital / 中国基层医药

Objective To detect the infection and subtype distribution of human papillomavirus (HPV) in cervical epithelial cell line in the People's Hospital of Jinhua.Methods 26 kinds of HPV genotypes were detected by gene chip,and the infection states among all subtypes were analyzed.Results A total of 25 genotypes of HPV were identified in 984 female patients,with the positive rate of 36.89％.The top three common high-risk HPV,ranging from high to low according to positive rate were HPV-16,58 and 52.The positive rates of high-risk HPV,low-risk HPV and multiple infection rate were 25.91％,5.69％ and 5.28％,respectively.The positive rates of the age groups of 21-30 years,＞ 30-40 years and ＞ 40 years were 42.33 ％,35.23％ and 35.94％,respectively.There were significant differences among the three age groups in the detection rate of high-risk HPV,low-risk type and multiple infection rate(x2 =71.58,P ＜ 0.05).Conclusion HPV 16,58 and 52 are the main high-risk genotypes of the 984 women in our hospital.The genotyping of HPV has important significance in the prevention,treatment and etiology of cervical cancer,as well as in the study of HPV vaccine.

Application of human papillomavirus 16/18 E6 protein detection for cervical cancer screening / 肿瘤研究与临床

Objective To evaluate the diagnostic accuracy and efficacy on cervical precancerous lesions and cervical cancer by HPV 16/18 E6 protein detection. Methods A total of 439 females with sexual activities were selected from Department of Gynaecology in Shanxi Cancer Hospital from May 2014 to January 2015, including 299 cases of cervical intraepithelial neoplasia (CIN)Ⅱ, CINⅢ or cervical cancer (the case group), and the other 140 cases (the control group). All the patients accepted the thinprep cytology test (TCT), HPV DNA and HPV 16/18 E6 oncoprotein tests and colposcope examination. Results The positive rates of the TCT, HPV DNA, HPV 16/18 E6 oncoprotein in the case group were 97.0 % (290/299), 94.3 % (282/299) and 66.9 % (200/299), respectively, and those in the control group were 44.3 % (62/140), 21.4 % (30/140) and 2.9%(4/140), respectively, and there were significant differences between both groups (all P<0.05). The sensitivity and specificity of the HPV 16/18 E6 oncoprotein test in detecting CINⅡ and above were 66.9 %and 97.1 %, respectively, and both of HPV DNA test were 94.3 % and 78.6 %, respectively; The consistent rate between HPV 16/18 E6 and HPV DNA was 71.9 % (κ= 0.21). In the case group, when TCT was associated with HPV DNA test, the sensitivity, specificity and accuracy were 98.9%, 82.8%and 81.7%, respectively, and when TCT was combined with HPV 16/18 E6 oncoprotein test, those were up to 97.9 %, 97.1 % and 95.0 %. Conclusion HPV 16/18 E6 oncoprotein test can improve the specificity of cervical cancer screening, so it may be used as a primary screening method in the less developed areas where HPV DNA test is difficult to be carried out, or as a shunt method for HPV DNA positive patients, which will allocate the limited health resources rationally.

Effects of Euphorbiae ebracteolatae Radixon the proliferation and apoptosis in human papillomavirus-18-infected HeLa cells / 国际中医中药杂志

ObjectiveTo investigate effects ofEuphorbiae ebracteolatae Radixon the proliferation and apoptosis in human papillomavirus (HPV)-18-infected HeLa cells.MethodsThe alcohol extract ofEuphorbiae ebracteolatae Radixwas prepared. Cell proliferation was determined using the MTT assay, and apoptotic cells was determined using the Hoechst 33258 staining.ResultsHPV-18-infected HeLa cells were treated with 10, 20 μg/mlof the alcohol extract ofEuphorbiae ebracteolatae Radixfor 12 h, the cell proliferation inhibition rate were significantly increased compared to the control group (16.36% ± 5.06%, 18.59% ± 5.99%; allP<0.01);HPV-18-infected HeLa cells were treated with 0.625, 1.25, 2.5, 5, 10, 20 μg/ml of the alcohol extract ofEuphorbiae ebracteolatae Radixfor 72 h, the cell proliferation inhibition rate were significantly increased compared to the control group (13.82% ± 3.66%, 30.24% ± 6.58%, 43.29% ± 4.29%, 53.32% ± 1.41%, 54.24% ± 1.97%, 50.68% ±1.74%;allP<0.01). The Hoechst 33258 staining showed that HPV-18-infected HeLa cells were treated with 10 μg/ml of the alcohol extract ofEuphorbiae ebracteolatae Radixfor 24 h, the apoptotic cells were found.ConclusionEuphorbiae ebracteolatae Radixcould inhibit the proliferation and induce apoptosis in HPV-18-infected HeLa cells.

In Silico Docking to Explicate Interface between Plant-Originated Inhibitors and E6 Oncogenic Protein of Highly Threatening Human Papillomavirus 18

The leading cause of cancer mortality globally amongst the women is due to human papillomavirus (HPV) infection. There is need to explore anti-cancerous drugs against this life-threatening infection. Traditionally, different natural compounds such as withaferin A, artemisinin, ursolic acid, ferulic acid, (-)-epigallocatechin-3-gallate, berberin, resveratrol, jaceosidin, curcumin, gingerol, indol-3-carbinol, and silymarin have been used as hopeful source of cancer treatment. These natural inhibitors have been shown to block HPV infection by different researchers. In the present study, we explored these natural compounds against E6 oncoprotein of high risk HPV18, which is known to inactivate tumor suppressor p53 protein. E6, a high throughput protein model of HPV18, was predicted to anticipate the interaction mechanism of E6 oncoprotein with these natural inhibitors using structure-based drug designing approach. Docking analysis showed the interaction of these natural inhibitors with p53 binding site of E6 protein residues 108-117 (CQKPLNPAEK) and help reinstatement of normal p53 functioning. Further, docking analysis besides helping in silico validations of natural compounds also helped elucidating the molecular mechanism of inhibition of HPV oncoproteins.

Prevalence of cervical squamous intraepithelial lesion high grade according to age from Antônio Pedro University Hospital / Prevalência de lesão intraepitelial escamosa de alto grau do colo uterino de acordo com a faixa etária no Hospital Universitário Antônio Pedro

The targeted population for HPV infection has peak infection at young adults, but studies point to the emergence of a new peak of viral infection and injuries later, probably by changesin sexual behaviour, waning immunity over time or reactivation of latent infection. Whereas the cervical squamous intraepithelial lesion high grade, mainly cervical intraepithelial neoplasia grades III (CIN III) have significant potential for progression to invasive carcinoma, the procedures of choice for the diagnosis and treatment in the target population are essential for the prevention of cervix cancer. Objective: To determine the prevalence of CIN II/III among patients seen in Cervical Pathology Clinic of Gynecology Department at the University Hospital Antonio Pedro from May 1996 to May 2013, relating toage in which this diagnosis was made. Method: It was selected patients referred to the Cervical Pathology Clinic for altered cytology and diagnosed through biopsy guided by colposcopy with CIN II / III. They were segmented into the following age groups: 15 to 24, 25 to 34, 35 to 44, 45 to 54, 55 to 64, 65 to 74, 75 to 84 and 85 to 94 years old. Results: Between 25 and 64 years of age, there were 36.5% of patients in these age groups with CIN II/III. However, it was found that 19% of patients younger than 25 years and 14.2% at 64 years also had such a diagnosis. Conclusion: The target population according to Brazilian Ministry of Health would let 16.2% of women with high-grade lesions withouta diagnosis, which corresponds to 11.3% of all high-grade cervical lesions.

A população alvo de infecções pelo HPV tem como pico adultos jovens, porém estudos apontam para um novo pico mais tardio, provavelmente por alterações do comportamento sexual, diminuição da imunidade ou reativação da infecção latente. Considerando que as lesões intraepiteliais escamosas de alto grau do colo uterino, sobretudo a neoplasia intraepitelial cervical grau III (NIC III) tem potencial significativo de progressão para carcinoma invasor,os procedimentos de escolha para diagnóstico e tratamento na população alvo são essenciais para a prevenção do câncer de colo uterino. Objetivo: Verificara prevalência de NIC II/III dentre as pacientes atendidas no Ambulatório de Patologia Cervical do Serviço de Ginecologia do Hospital Universitário Antônio Pedro no período de maio de 1996 a maio de 2013, relacionando com a faixa etária em que este diagnóstico foi realizado. Método: Selecionou-se as pacientes encaminhadas ao Ambulatório de Patologia Cervical por citologia oncótica alterada e diagnosticadas, por meio de biópsia dirigida pela colposcopia, comNIC II/III. Foram segmentadas nas seguintes faixas etárias: 15 a 24, 25 a 34, 35 a 44, 45 a 54, 55 a 64, 65 a 74, 75 a 84 e 85 a 94 anos. Resultados: Entre 25e 64 anos de idade, houve 36,5% de pacientes nestas faixas etárias com NIC II/III. Entretanto, verificou-se que 19% de pacientes com menos de 25 anos e14,2% com mais de 64 anos também apresentavam tal diagnóstico. Conclusão: A população-alvo preconizada pelo Ministério da Saúde deixaria 16,2% dasmulheres com lesões de alto grau à margem de um diagnóstico, o que corresponde a 11,3% de todas as lesões de alto grau do colo uterino.

Conhecimento e atitude de usuários do SUS sobre o HPV e as vacinas disponíveis no Brasil / SUS users? knowledge of and attitude to HPV virus and vaccines available in Brazil / SUS users? knowledge of and attitude to HPV virus and vaccines available in Brazil

OBJETIVO : Analisar o conhecimento de homens e mulheres acerca do HPV e das vacinas e sua intenção de serem vacinados e de vacinarem seus filhos adolescentes. MÉTODOS : Estudo descritivo, de corte transversal, com 286 mulheres (18 a 49 anos) e 252 homens (18 a 60 anos), usuários de cinco unidades básicas de saúde e duas policlínicas do Sistema Único de Saúde, em Campinas, SP, em 2011. Foi realizada entrevista estruturada. Realizou-se análise bivariada e regressão de Poisson para identificar variáveis associadas ao conhecimento sobre HPV e vacinas e à intenção de vacinação. RESULTADOS : Quase 40,0% dos entrevistados referiram ter ouvido falar do HPV e 28,9% mencionaram informações adequadas; a principal fonte de informação foi a mídia (41,7%); 8,6% tinham ouvido falar das vacinas. Depois de informados da existência das vacinas, cerca de 94,0% dos participantes disseram que se vacinariam e/ou vacinariam filhos adolescentes se as vacinas estivessem disponíveis na rede pública de saúde. Escolaridade > 8 anos e ser do sexo feminino estiveram independentemente associados a ter ouvido falar do HPV e das vacinas e a ter conhecimento adequado sobre o vírus. Maior idade associou-se a ter ouvido falar das vacinas. Não houve variáveis associadas à intenção de vacinação. CONCLUSÕES : Os resultados reforçam a necessidade de haver intervenções educativas na população para prover informação adequada sobre o HPV e sobre medidas de prevenção. .

Objetivo : Analizar el conocimiento de hombres y mujeres sobre el VPH y de las vacunas y su intención de ser vacunados y de vacunar sus hijos adolescentes. Métodos : Estudio descriptivo, de corte transversal, con 286 mujeres (18 a 49 años) y 252 hombres (18 a 60 años), usuarios de cinco unidades básicas de salud y dos policlínicas del Sistema Único de Salud, en Campinas, SP – Brasil, en 2011. Se realizó entrevista estructurada. Se utilizó el análisis bivariado y regresión de Poisson para identificar variables asociadas al conocimiento sobre VPH y vacunas y la intención de vacunación. Resultados : Casi el 40,0% de los entrevistados mencionaron haber oído hablar del VPH y 28,9% relataron informaciones adecuadas; la principal fuente de información fueron los medios de comunicación (41,7%); 8,6% habían oído hablar de las vacunas. Después de informados de la existencia de las vacunas, cerca de 94,0% de los participantes dijeron que se vacunarían y/o vacunarían hijos adolescentes si las vacunas estaban disponibles en la red pública de salud. Escolaridad > 8 años y ser del sexo femenino estuvieron independientemente asociados al haber oído hablar del VPH y de las vacunas y tener conocimiento adecuado sobre el virus Mayor edad se asoció al haber oído hablar de vacunas. No hubo variables asociadas a la intención de vacunación. Conclusiones : Los resultados refuerzan la necesidad de haber intenciones educativas en la población para proveer información adecuada sobre el VPH y sobre medidas de prevención .

OBJECTIVE : To investigate knowledge of HPV and HPV vaccines in men and women, users of the Brazilian Unified Health System, and the intention to get themselves and their teenage children vaccinated. METHODS : A descriptive, cross-sectional study with 286 women (18-49 years old) and 252 men (18-60 years old), users of five primary health units and two polyclinics in Campinas, SP, Southeastern Brazil, was carried out. Participants were interviewed in 2011 using a structured questionnaire. Bivariate and Poisson regression analysis were performed to identify variables associated with knowledge of HPV and HPV vaccines, and participants vaccination intentions. RESULTS : Almost 40.0% of the participants reported having heard of HPV and 28.9% mentioned adequate information. The main information source was the media (41.7%). Only 8.6% of the participants had heard of the HPV vaccines. Once the participants were informed of the existence of HPV vaccines about 94% of them said they would get vaccinated and/or vaccinate their teenage children, if the vaccines were available in the public health system. Schooling of over 8 years and being female were the variables independently associated with having heard of HPV, the vaccines and having adequate knowledge of the virus. Advanced age was associated with having heard of HPV vaccines. There were no variables associated with the vaccination intentions. CONCLUSIONS : These results reinforce the need for educational activities that provide the population with adequate information on HPV and preventive measures. .

Expression and clinical significance of HPV16/18, p16, Her-2 in squamous cell cervical carcinoma / 肿瘤研究与临床

Objective To study the expression of HPV、p16 and Her-2 in the squamous cell cervical carcinoma and its chnical significance. Methods Expression of HPV16/18、p16, and C-erbB-2 and the amplification of Her-2 gene were examined using situ hybridization technique,SP immunohistochemistry,and FISH imaging analysis system in 60 cases of cervical cancer, 61 cases of CIN, and 21 cases of normal cervical tissue,respectively.Results The positive rates of HPV16/18 and p16 in the normal tissue,CIN Ⅰ -Ⅱ,CINⅢ and the squamous cell cervical carcinoma were gradually increased, they wereo (0/21),9.68 ％ (3/31),46.67 ％ (14/30),71.67 ％ (43/60);0 (0/21),19.35 ％ (6/31),93.33 ％ (28/30),96.67 ％ (58/60),respectively,and there were significant differences among the groups (P＜0.05),but no significant difference was found between the normal tissue and the CIN Ⅰ - Ⅱ. The positive rates of Her-2 and Her-2 in the CIN Ⅲ and the carcinoma were 13.33 ％ (4/30),31.67 ％ (19/60),3.33 ％ (1/30),21.67 ％ (13/60),respectively,but in the normal group and the CIN Ⅰ - Ⅱ wereo,and the differences between the carcinoma group and the CIN group,the carcinoma group and the normal group were significant(P＜0.05).The expression of Her-2 and the amplification of Her-2 were closely related to the stage, degree of differentiation and metastasis of lymph node in the squamous cell cervical carcinoma (P＜0.05). Conclusion The infection of HPV is one of thetriggers for the squamous cell cervical carcinoma.The expression of p16 and the amplification of Her-2 may be closely correlated with tumor development and high expression of p16 and Her-2 indicates poor prognosis.

Primary study on the signal transduction concerned human papillomavirus 18 E6 oncoprotein / 中华微生物学和免疫学杂志

Objective To explore the relationship of signal transduction among human papillomavirus 18 E6 oncoprotein (HPV18E6), signal transducers and activators of transcription 1 (STAT1), protein kinase R( PKR )/α subunit of eukaryotic initiation factor 2 ( eIF2α ), nuclear factor-kappa Bp65 ( NF-κBp65 ), mitogen-activated protein kinase( MAPK)/c-Jun N-terminal kinase(JNK) ,and possible molecular mechanism. Methods Construct two lentiviral vectors which contain shRNA interfering sequence aiming at the targets of HPV18E6 oncogene and NC sequence( HPV18E6-RNAi-LV, NC-GFP-LV), based on the transduction with HPV18E6-RNAi-LV and NC-GFP-LV into HeLa cell to interfere the expression of HPV18E6 oncogene and NC sequence,the expressions of mRNA and protein( including phosphating patem)of HPV18E6, STATI, PKR, eIF2α, NF-κBp65, MAPK, JNK are measured with RT-PCR and Western blot, the difference of proliferation and sensitivity to carboplatin of HeLa cell are determined with Transwell cell methods and MTT among every groups. Results The expression of HPV18E6 oncogene can affect the expression level of mRNA and protein of NF-κBp65 and PKR genes, also affect phosphating levels of phosphating protein p-STAT1, p-PKR and p-eIF2α;the restraining rates of proliferation and sensitivity to carboplatin of HeLa cell are higher in HPV18E6-RNAi-LV group than the other groups( P＜0. 05 or P＜0.01 ). Conclusion HPV18E6 oncoprotein not only reduces the expression of PKR but dephosphorylates p-STAT1, pPKR and p-eIF2α to restrain activation of PKR/eIF2α signal transduction passage, maintain the proliferation and invading ability of HeLa cell and restrain apoptosis. The signal transduction among HPV18E6, MAPK/JNK are not clear.

Is human papillomavirus genotype an influencing factor on radiotherapy outcome? Ambiguity caused by an association of HPV 18 genotype and adenocarcinoma histology / 부인종양

OBJECTIVE: To evaluate whether human papillomavirus (HPV) genotype is associated with poor prognosis of uterine cervical cancer treated primarily with radiotherapy. METHODS: HPV genotyping was performed in 181 radiotherapy patients using SPF10 polymerase chain reaction and HPV reverse hybridization line probe assay. Univariate and multivariate Cox regression analysis was performed to explore the prognostic factors. Bivariate analysis was performed to investigate any association between HPV genotype and the rest of the prognostic factors. RESULTS: HPV type 18 was associated with poor disease-free survival on univariate analysis but the statistical significance was abolished when multivariate analysis was applied. Bivariate analysis was performed to examine the possible confounding factors influencing the effect of HPV 18 on prognosis. As a result, adeno/adenosquamous carcinoma histology reduced the prognostic importance of HPV 18 by 66% (2.4 to 1.6), and was the only factor which reduced the hazard ratio of HPV 18. When compared to non-18 squamous cell carcinoma, type 18 increased the risk of recurrence up to 4-fold in adeno/adenosquamous/HPV 18 and 3.7 in adeno/adenosquamous/non-18, and to 2-fold in squamous carcinoma/HPV 18, respectively. CONCLUSION: Our data suggest that the prognostic significance of HPV 18 genotype is substantial on radiotherapy outcome, but can be underestimated because of the close association of the HPV 18 and adenocarcinoma/adenosquamous carcinoma histology. Both HPV 18 and histologic type should be regarded as strong prognostic factors in considering the treatment outcome of the uterine cervical cancer.

Recent research advances between HPV and cervical cancer / 国际肿瘤学杂志

Human papillomavirus is a DNA virus that can induce uterine cervical neoplasms, especially the high-risk and mixed infection. In this review, the progress on HPV feature and carcinogenic mechanisms,molecular detection on uterine cervical neoplasms and papillomavirus vaccines is discussed.

Phylogenetic classification of human papillomavirus genotypes in high-grade cervical intraepithelial neoplasia in women from a densely populated Brazilian urban region / Classificação filogenética dos genótipos de papilomavírus humano em neoplasia intraepitelial cervical de alto grau em mulheres de uma região urbana brasileira densamente povoada

CONTEXT AND OBJECTIVE: Differences in human papillomavirus (HPV) types may correlate with the biological potential and invasion risk of high-grade cervical intraepithelial neoplasia (CIN 2 and CIN 3). The objective of this study was to determine the relationship between different combinations of HPV types and CIN severity. DESIGN AND SETTING: Cross-sectional study, at Universidade Estadual de Campinas (Unicamp). METHODS: Cervical samples from 106 women treated due to CIN 2 (18) or CIN 3 (88) were examined for specific HPV genotypes using Roche Linear Array® (LA-HPV). The proportions of CIN 2 and CIN 3 in groups of women infected with the HPV phylogenetic groups A7 and A9 were compared. Three groups were formed: women with single infections; multiple infections; and the whole sample. RESULTS: Multiple infections were detected in 68 samples (64.7 percent). The most frequent high-risk genotypes detected (single/multiple) were HPV 16 (57.1 percent), HPV 58 (24.7 percent), HPV 33 (15.2 percent), HPV 52 (13.3 percent), HPV 31 (10.4 percent), HPV 51 (7.6 percent) and HPV 18 (6.6 percent). Women without infection with HPV species Alpha 9 were less likely to have CIN 3 than were their Alpha 9 HPV-infected counterparts. HPV 16 and/or HPV 18, with or without associations with other viral types, were more frequently found in women with CIN 3 than in those with CIN 2. CONCLUSIONS: The severity of high-grade CIN may be aggravated by the presence of HPV types included in the Alpha 9 phylogenetic classification and by infections including HPV 16 and 18, singly or in combination with other HPV genotypes.

CONTEXTO E OBJETIVO: Diferentes tipos de papilomavírus humano (human papillomavirus, HPV) podem ser correlacionados com a capacidade biológica e risco de invasão das neoplasias intra-epitelial de alto grau cervical (NIC 2 e NIC 3). O objetivo deste estudo foi determinar a relação de diferentes tipos de HPV com a gravidade da NIC. TIPO DE ESTUDO E LOCAL: Estudo transversal na Universidade Estadual de Campinas (Unicamp). MÉTODOS: Foram avaliados os genótipos específicos de HPV da amostra cervical de 106 mulheres com NIC 2 (18) ou NIC 3 (88), utilizando Roche Linear Array® (LA) HPV genotyping assay. Foram comparadas as proporções de NIC 2 e NIC 3 em grupos de mulheres infectadas com tipos de HPV dos grupos filogenéticos A7 e A9. Três grupos foram formados: mulheres com infecção simples; infecção múltipla; e infecção simples e múltipla. RESULTADOS: Infecções múltiplas foram detectadas em 68 (64,7 por cento) das amostras. Os genótipos de alto risco mais frequentemente detectados em infecção simples ou múltipla foram HPV 16 (57,1 por cento), HPV 58 (24,7 por cento), HPV 33 (15,2 por cento), HPV 52 (13,3 por cento), HPV 31 (10,4 por cento), HPV 51 (7,6 por cento) e HPV 18 (6,6 por cento). A probabilidade de mulheres com NIC 3 serem infectadas com HPV que não da espécie Alfa 9 era menor do que com os tipos de HPV da espécie Alfa 9. HPV 16 e ou 18, associado ou não com outros tipos virais eram mais frequentemente encontrados nas mulheres com NIC 3 do que naquelas com NIC 2. CONCLUSÃO: A gravidade da NIC de alto grau pode ser aumentada pela presença de tipos de HPV incluídos na classificação filogenética Alfa 9 e por infecções que incluem HPV 16 e 18 combinados ou não com outros genótipos de HPV.