Factors Associated with Presence of Human Papillomavirus Infection among Women: Findings from New Cervical Cancer Screening in Kelantan, Malaysia

@#Introduction: Human papillomavirus (HPV) infection is known to cause cervical cancer worldwide. Recently, Malaysia introduced HPV DNA detection testing for cervical cancer screening program. However, knowledge regarding factors for HPV infection among women still limited. Thus, this study aimed to determine the prevalence and factors associated with HPV infection among women in Kelantan, a north-eastern state of Malaysia. Methods: This study used secondary data extracted from HPV DNA test registry book and HPV DNA laboratory request forms. Data on all Malaysian women aged 30 to 49 years old in 2019 reported in registry book were included. Simple random sampling was applied. All information from book and forms were collected using proforma and analysed using SPSS. The outcomes were categorised into HPV infection and non-HPV infection. The parameters related to factors associated with HPV infection were determined using multivariable logistic analysis. Results: The prevalence of HPV infection among women attending the new cervical screening was 8.4% (95% CI 6.4%, 10.3%). Those aged between 30 and 39 years old (AdjOR 2.09; 95% CI 1.16, 3.78, p=0.014), had 5 or more parities (AdjOR 2.82; 95% CI 1.58, 5.06, p<0.001) and hormonal contraception users (AdjOR 7.48; 95% CI 4.07, 13.76, p<0.001) were significantly associated with HPV infection. Conclusion: Overall, the prevalence of HPV infection from this study is comparable to the local and international studies. Age, number of parities and hormonal contraception users influence the HPV infection. This finding could help in designing more targeted screening for cervical cancer.

Clinical significance of high-risk HPV-DNA detection combined with TCT in screening and follow-up of cervical lesions / 上海预防医学

ObjectiveTo explore the application value of high-risk HPV-DNA detection combined with TCT in cervical lesion screening and follow-up. MethodsThis study was conducted from February 2019 to February 2021. During this period， 241 subjects who were the patients referred from the primary community hospitals to the center for re-examination of cervical lesions. Of which 80 were patients with cervical intraepithelial neoplasia. Liquid-based cytology （TCT） technology was used to examine the cervical cytological morphology. The second-generation high-throughput sequencing technology and time-of-flight mass spectrometry technology， independently developed by BGI， were used to screen for HPV-DNA typing. At the same time， biopsy sampling was carried out， and the final pathological diagnosis was made. TCT detection and combined HPV-DNA detection were performed on 80 patients to compare the relationship between TCT alone and TCT/HPV-DNA combined test for the diagnosis and prognosis of CIN Ⅱ and CIN Ⅲ. Follow-up was conducted， and the HPV infection and TCT were re-tested. ResultsAmong the 80 cases of cervical intraepithelial neoplasia， 41 cases （51.25%） were between 35 and 44 years old， higher than the other age groups （P<0.001）. Compared with either TCT or HPV-DNA， TCT combined with HPV-DNA had obvious advantages in sensitivity， specificity， positive predictive value， and negative predictive value （P<0.05）. The recurrence rate in CIN Ⅱ and CIN Ⅲ groups was 9.52% and 16.67% respectively after 18 months of the follow-up. ConclusionTCT detection plays a positive role in cervical pre-cancer screening. By combining high-risk HPV-DNA typing and TCT detection， the detection values of sensitivity and specificity are significantly higher， which can improve the accuracy of cervical lesion screening and is of great significance for the follow-up work.

Detection of HPV DNA in vaginal samples self-collected by women living with HIV treated through the Brazilian public health system: Prevalence and analysis of risk factors

ABSTRACT Background: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. Methods: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. Results: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). Conclusions: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.

Analysis of cervical liquid-based cytology results in Eskişehir, Turkey: correlation of cytology results with histology, immunocytocemical HPV Ab and HPV DNA results of 18404 women

Background: To analyze retrospectively the results of HPV DNA, immunocytochemical HPV antibody staining of gynecologic smear samples evaluated in a public hospital and to observe their compatibility with histologic diagnosis. At the same time, the contribution of ICC HPV Ab staining experience results to the morphological evaluation is discussed in this paper.Methods: In this study, liquid-based cytology test results of patients who applied to the gynecology between 2014 and 2017 were analyzed. The Ultravision Quanto Detection System was modified for immunocytochemical staining. HPV DNA tests were performed with the Qiagen Hybrid Capture test.Results: The 18404 test result was included in the research. The percentage of smear that epithelial cell atypia is seen was 3.4%, the rate of ASC/SIL was 1.89%. Compared to the first 3 years of the study, the increase in the rate of LSIL is seen with a partial decrease in ASCUS rate in year 2017 (p<0.05). The atypical positive test rate with histologic confirmation was 73.61%. Among 138 HPV Ab results, 58.7% of them were negative and 41.3% of them were positive. Sensitivity and specificity rates were determined 76.19% and 52.17% for SIL. Among 53 HPV DNA results (53% negative and 46.3% positive); sensitivity and specificity rates were determined 92.86% and 50% for SIL.Conclusions: İmmunocytochemical HPV Ab staining provided statistically significant contribution to LSIL (p<0.05). It is thought that it also will provide additional evidence for morphological findings while cytological evaluation and may help the clinician in managing the conditions for disease.

Comparison of screening performance between primary high-risk HPV screening and high-risk HPV screening plus liquid-based cytology cotesting in diagnosis of cervical precancerous or cancerous lesions / 中华预防医学杂志

Objective@#To evaluate and compare the screening performance of primary high-risk HPV(HR-HPV) screening and HR-HPV screening plus liquid-based cytology (LBC) cotesting in diagnosis of cervical cancer and precancerous lesions (CIN2+).@*Methods@#We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. After obtaining informed consent, all women received liquid-based cytology(LBC)testing, HR-HPV DNA testing. Totally 28 777 women with complete LBC, HPV and biopsy results were included in the final analysis. Screening performance of primary HR-HPV DNA screening and HPV screening plus LBC co-testing in diagnosis of CIN2+ were calculated and compared among different age groups.@*Results@#Among the whole population, the detection rates of primary HR-HPV screening and HR-HPV screening plus LBC co-testing are 3.05% (879 CIN2+) and 3.13%(900 CIN2+), respectively. The sensitivity were 96.4% and 98.7% (χ2=19.00, P<0.001), and the specificity were 86.2% and 78.8% (χ2=2 067.00, P<0.001), respectively. Areas under the receiver operating characteristic (ROC) curve (AUC) showed that the primary HR-HPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z=6.16, P<0.001). Compared with primary HR-HPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ2=132.00, P<0.001) and the number of colposcopy examination for detecting per CIN2+ (5.4 and 7.6, respectively).In the group aged 25-29, the colposcopy referral rates was 8.7 (10.9%(199 cases) vs 1.3%(23 cases)) times as much as the detection rate of primary HR-HPV screening in diagnosis of CIN2+, and was 12.5 (15.7%(288 cases) vs 1.3%(23 cases)) times as much as the detection rate of HR-HPV screening plus cytology contesting.@*Conclusion@#Compared with primary HR-HPV screening, HR-HPV screening plus cytology co-testing does not show better results in the screening performance for CIN2+ detection, and the cost-effectiveness is not good enough, especially in younger age group.

Detection of High-Risk Human Papillomavirus in Cervix Sample in an 11. 3-year Follow-Up after Vaccination against HPV 16/18 / Detecção de papilomavírus humano de alto risco em amostras de colo uterino em 11. 3 anos de acompanhamento após vacinação contra HPV 16/18

Abstract Purpose the aim of this study was to evaluate the pattern of human papillomavirus (HPV) detection in an 11.3-year post-vaccination period in a cohort of adolescent and young women vaccinated or not against HPV 16/18. Methods a subset of 91 women from a single center participating in a randomized clinical trial (2001-2010, NCT00689741/00120848/00518336) with HPV 16/18 AS04- adjuvanted vaccine was evaluated. All women received three doses of the HPV vaccine (n = 48) or a placebo (n = 43), and cervical samples were collected at 6-month intervals. Only in this center, one additional evaluation was performed in 2012. Up to 1,492 cervical samples were tested for HPV-DNA and genotyped with polymerase chain reaction (PCR). The vaccine group characteristics were compared by Chi-square or Fisher exact or Mann-Whitney test. The high-risk (HR)-HPV 6-month-persistent infection rate was calculated. The cumulative infection by HPV group was evaluated by the Kaplan-Meier method and the log-rank test. Results the cumulative infection with any type of HPV in an 11.3-year period was 67% in the HPV vaccine group and 72% in the placebo group (p = 0.408). The longitudinal analysis showed an increase of 4% per year at risk for detection of HR-HPV (non-HPV 16/ 18) over time (p = 0.015), unrelated to vaccination. The cumulative infection with HPV 16/18 was 4% for the HPV vaccine group and 29% for the placebo group (p = 0.003). There were 43 episodes of HR-HPV 6-month persistent infection, unrelated to vaccination. Conclusions this study showed themaintenance of viral detection rate accumulating HR-HPV (non-HPV-16-18) positive tests during a long period post-vaccination, regardless of prior vaccination. This signalizes that the high number of HPV-positive testsmay be maintained after vaccination.

Resumo Objetivos avaliar o padrão de detecção do papilomavírus humano (HPV) em um período de 11.3 anos após a vacinação em uma coorte de adolescentes e mulheres jovens vacinadas ou não contra HPV 16/18. Métodos avaliou-se um subgrupo de 91 mulheres de um único centro, participantes de ensaio clínico randomizado (2001-2010, NCT00689741/00120848/00518336) com a vacina contra HPV 16/18 com adjuvante AS04. Todas as mulheres receberam três doses de vacina contra HPV (n = 48) ou placebo (n = 43), e tiveram amostras cervicais coletadas em intervalos de 6 meses. Somente neste centro, uma avaliação adicional foi realizada em 2012. Um total de 1.492 amostras cervicais foram testadas para DNA-HPV e genotipadas com reação em cadeia da polimerase (RCP). As características dos grupos de vacina contra HPV ou placebo foram comparadas pelo teste de Qui-quadrado ou teste exato de Fisher ou teste de Mann-Whitney. A infecção persistente por 6meses pelo HPV de alto risco (AR) foi calculada. A infecção cumulativa por grupo foi avaliada pelo método de Kaplan-Meier e pelo teste log-rank. Resultados a infecção cumulativa com qualquer tipo de HPV em11.3 anos foi de 67% no grupo vacina contra HPV e de 72% no grupo placebo (p = 0,408). A análise longitudinal mostrou um aumento de 4% ao ano no risco de detecção de HR-HPV (não-HPV 16/18) ao longo do tempo (p = 0,015), não relacionado com a vacinação. A infecção cumulativa com HPV 16/18 foi de 4% para o grupo vacina contra HPV e 29% para o grupo placebo (p = 0,003). Houve 43 episódios de infecção persistente por 6 meses por HR-HPV, não relacionados com a vacinação. Conclusões este estudo mostrou a manutenção da taxa de detecção viral, acumulando testes positivos de HR-HPV (não HPV-16-18) durante longo período pósvacinação, independentemente da vacinação prévia. Isto sinaliza que a alta positividade dos testes de HPV pode ser mantida após a vacinação.

Value of combined application of high risk human papillomavirus DNAdetection and thinprep cytologic test for cervical cancer screening / 中国生化药物杂志

Objective To evaluate the diagnostic value of thinprep cytologic test (TCT) combined with high-risk human papillomavirus (HR-HPV) DNA for cervical cancer (CC). Methods 141 cases of patients with abnormal cervical lesions were abnormal examined by TCT and were graded by the results of TCT and cervical biopsy, the HR-HPV-DNA was detected by surface plasmon resonance (SPR). Results The cervical biopsy positive rate 65.2% (92/141) was significantly higher than the positive rate of TCT 39.0% (55/141) (χ2=19.45, P < 0.05). The positive rate of HR-HPV-DNA was 66.0% (93/141) was significantly higher than the positive rate of TCT 39.0% (55/141), (χ2=20.53, P < 0.05). Conclusion TCT, HR-HPV-DNA and cervical biopsy are important clinical diagnostic methods for cervical lesions, combine detection of TCT and HR-HPV-DNA can improve the detection rate of cervical lesions.

Cervical cancer screening: from Pap smear to future strategies / Triagem de câncer do colo uterino: do teste de Papanicolaou a estratégias futuras

ABSTRACT Previously, the screening for detection of cervical cancer was performed by simple cervicovaginal sample collected by the physician whenever the patient attended the medical consultation, and soon it was established as the annual"Pap smear". Since then, an elementary test has evolved into a complex process with multiple algorithms for the identification of invasive disease. The detection of human papillomavirus (HPV) has become part of the new screening recommendations, resulting in major changes in the guidelines. This review intends to emphasize the most important topics that are part of cervical cancer screening, including cervical cytology and HPV detection, and to discuss particular aspects of cervical cancer in Brazil. Despite the great benefits achieved by the cervical cancer screening programs with cytology and HPV test, there are still important issues to be discussed and improved in defining future strategies, including simplicity and possible application in different socioeconomic contexts, definition of the best test or tests to be applied and recommended interval, minimizing possible harms. After the establishment of screening algorithms well defined by leading organizations, management protocols should be disseminated among physicians and patients by education programs.

RESUMO Inicialmente, a triagem para detecção do câncer de colo uterino era feita por meio de uma simples amostra cervicovaginal colhida pelo médico, sempre que o paciente comparecia à consulta médica; logo se estabeleceu como"exame de Papanicolaou" anual. Desde então, um teste elementar evoluiu para um processo complexo, com múltiplos algoritmos para identificação de doença invasiva. A detecção do papilomavírus humano (HPV) tornou-se parte das novas recomendações de triagem, resultando em grandes mudanças nas diretrizes. Esta revisão pretende enfatizar os tópicos mais importantes que fazem parte do rastreamento do câncer de colo do útero, incluindo citologia cervical e detecção do HPV, bem como discutir aspectos particulares do câncer de colo do útero no Brasil. Apesar dos grandes benefícios alcançados pelos programas de rastreamento do câncer de colo uterino por meio do uso da citologia e do teste de HPV, existem ainda pontos importantes a serem discutidos e melhorados na definição de estratégias futuras, como simplicidade e possível aplicação em diferentes contextos socioeconômicos, definição do melhor teste ou testes a serem aplicados e intervalo recomendável, minimizando possíveis danos. Após o estabelecimento de algoritmos de rastreamento bem definidos pelas principais organizações, protocolos de manejo devem ser divulgados entre médicos e pacientes por programas de educação.

Incidence of Cervical Human Papillomavirus and Cervical Intraepithelial Neoplasia in Women with Positive and Negative HIV Status / Incidência de infecção cervical pelo vírus papiloma humano e neoplasia intraepitelial cervical em mulheres com sorologia positiva e negativa para o HIV

Abstract Objectives To evaluate the incidence and factors associated with cervical intraepithelial neoplasia (CIN) and cervical infection by human papillomavirus (HPV) among HIV-positive and HIV-negative women. Methods A cohort of 103 HIV positive and 113 HIV negative women were monitored between October 2008 and February 2012, for at least one year. Procedures included cervical cytology, DNA/HPV detection by polymerase chain reaction, colposcopy with biopsy if necessary, followed by an interview for exposure characteristics data. CIN was based on the histopathological results. Results The incidence of CIN was of 8.8 and 4.6 cases/100 women-years in HIVpositive and HIV-negative women, respectively. HIV-positive women presented a hazard ratio (HR) of 2.8 for CIN and developed lesions earlier (0.86 year) than HIVnegative women (2 years) (p = 0.01). The risk of developing CIN decreased with age (HR = 0.9) and marital status (HR = 0.4). HPV patients presented a higher incidence of CIN when compared HIV-positive and HIV-negative women (p = 0.01). The incidence of HPV cervical infection was 18.1 and 11.4 cases/100 women-years in HIV-positive and HIV-negative women, respectively. Those HIV-positive presented earlier HPV infection (p = 0.002). The risk of developing HPV infection decreased with age and was higher among HIV-positive women. HPV 16 was the most common type in HIV-positive women, and also the type most closely associated with CIN in HIV-negative women. Conclusions HIV-positive women had a greater incidence of HPV and CIN, and in a shorter time interval. More rigorous and timely clinical control is required for this group.

Resumo Objetivos Avaliar a incidência e fatores associados com neoplasia intraepitelial cervical (NIC) e infecção cervical pelo Papiloma Vírus Humano (HPV) entre mulheres HIV positivas e negativas. Métodos Coorte de 103 mulheres positivas para o HIV e 113 negativas, que foram acompanhadas entre outubro de 2008 a fevereiro de 2012, com seguimento mínimo de um ano. Os procedimentos realizados foram coleta de material cervical para citologia oncótica e detecção do DNA/HPV pela reação em cadeia da polimerase, colposcopia seguida de biópsia, se necessário, e entrevista para obter dados e características de exposição. O diagnóstico de NIC foi baseado no resultado histopatológico das biópsias. Resultados A incidência pessoas-tempo de NIC foi de 8,8 e 4,6 casos/100 mulheresano para as mulheres HIV-positivas e HIV-negativas, respectivamente. As HIV-positivas apresentaram uma razão de risco (HR) de 2,8 para NIC e desenvolveram lesões mais precocemente (0,86 ano) do que as negativas (2 anos) (p = 0,01). O risco de desenvolver NIC diminuiu com a idade (HR = 0,9) e o estado civil (HR = 0,4). Pacientes com HPV apresentaram maior incidência de NIC, quando comparadas as mulheres HIVpositivas e as negativas (47,6 10,5%) (p = 0,01). A incidência de infecção cervical pelo HPV, por pessoa/tempo, foi de 18,1 e 11,4 casos/100 mulheres-ano, respectivamente para mulheres HIV-positivas e negativas. As HIV-positivas apresentaram HPV mais precocemente (p = 0,002). O risco de apresentar HPV diminuiu com a idade e foi maior entre as HIV-positivas. O HPV 16 foi o tipo mais comum entre as mulheres HIVpositivas. Conclusões As mulheres HIV-positivas tiveram maior incidência de HPV e NIC, e um menor intervalo de tempo. Controle clínico mais rigoroso e oportuno é requerido para este grupo.

HPV detection in floor of mouth squamous cell carcinoma by PCR amplification / Detecção do HPV em carcinoma espinocelular de assoalho de boca por amplificação da PCR

ABSTRACT Introduction: Studies conducted during the last years, using new technologies for viral detection, permit to consider human papillomavirus (HPV) an etiologic factor for cervical cancer. Besides the relation to genital regions, other anatomic sites have been associated with HPV, including head and neck regions. Objectives: To investigate the prevalence of HPV infection in 35 samples from paraffin-embedded tissues using polymerase chain reaction (PCR)-deoxyribonucleic acid (DNA) amplification, and correlate it with demographic, clinical, and morphological factors and prognosis. Materials and methods: All samples were first amplified with human β-globin gene primers. Samples with positive amplification were subjected to HPV-DNA detection with general GP5 and GP6 primers. Results Only 30 samples were amplified for the β-globin gene. No floor of mouth squamous cell carcinoma cases showed amplification of HPV DNA. Discussion: The absence of HPV-DNA amplification does not suggest that this virus is absent from the process of oral carcinogenesis, since the selected sample is not in the risk group for the development of oral cancer associated with HPV infection. Conclusions: No correlation was found between HPV infection and floor of mouth carcinogenesis, however further studies are necessary.

RESUMO Introdução: Estudos realizados durante os últimos anos permitem considerar a infecção pelopapilomavírus humano (HPV) um fator etiológico para o câncer cervical. Apesar da íntima relação desse vírus com as regiões genitais, outras localizações anatômicas têm sido associadas a tal infecção, inclusive as regiões de cabeça e pescoço. Objetivos: Investigar a prevalência da infecção pelo HPV em 35 amostras parafinadas de carcinoma espinocelular de assoalho de boca, utilizando a amplificação da reação em cadeia dapolimerase (PCR) como método de detecção do ácido desoxirribonucleico (DNA) viral, bem como correlacionar aspectos demográficos, clínicos e morfológicos com o prognóstico da doença. Materiais e métodos: Todas as amostras foram inicialmente amplificadas com o primerpara detecção do gene da β-globina humana. As que tiveram amplificação positiva para o gene da β-globina foram então submetidas à detecção do DNA viral com os primers GP5 e GP6. Resultados: Apenas 30 amostras foram amplificadas para o gene β-globin. Nenhuma das amostras de carcinoma de assoalho de boca demonstrou resultado positivo para amplificação do DNA viral. Discussão: Apesar de a influência do vírus na carcinogênese oral não ter sido comprovada devido à ausência de DNA viral nas amostras, a relação não pode ser descartada, uma vez que as amostras selecionadas não se encontravam em grupo de risco para o desenvolvimento de carcinoma espinocelular de boca associado à infecção pelo HPV. Conclusão: Não foi detectada relação entre a infecção pelo HPV e o carcinoma de assoalho de boca, no entanto mais estudos são necessários sobre o tema.

The clinical value of HPV E6/E7 mRNA and HPV DNA in early screening of cervical cancer / 天津医药

Objective To analyze the differences of positive detection rate and copy number of human papillomavirus (HPV) DNA and E6/E7 mRNA between different grades of cervical lesions, and evaluate their clinical values in early screen?ing of cervical cancer. Methods The cervical exfoliated cell samples from 154 women undergoing biopsy examination and 32 objects undergoing hysterectomy (control group) were collected in Tianjin Central Hospital of Gynecology Obstetrics in 2014. According to the pathological results of cervical biopsy, 154 samples were divided into low-grade squamous intraepi?thelial lesion group (LSIL, n=51), high-grade squamous intraepithelial lesion group (HSIL, n=71), and squamous cell carci?noma group (SCC, n=32). HPV DNA was tested with hybrid capture technology, and E6/E7 mRNA was detected with fluores?cence quantitative hybridization. Immunohistochemistry was performed by detecting E6/E7 protein in all patients after sur?gery or cervical biopsy. Results Combined results of HPV DNA and E6/E7 mRNA demonstrated that the positive detection rate was significantly lower in control group than that of all levels of lesion groups (P 10 000 E6/E7 were significantly increased in high-grade squamous intraepithelial lesion group. Immunohistochemical results showed that the positive detection rate of E6/E7 was significantly lower in control group than that of all levels of lesion groups (P<0.05). The positive rate of E6/E7 was significantly higher in the high-grade squa?mous intraepithelial lesion group than that of low-grade group (P<0.05). Conclusion HPV infection is closely related to cervical abnormalities, which is one of effective measures for early screening of cervical cancer. The negative result of HPV DNA is very helpful to exclude the cervical abnormality, whereas the positive detection of mRNA has great value in predict?ing the disease. Combined results of positive detection and copy number make a comprehensive evaluation for the risk of cer?vical lesions.

Focal epithelial hyperplasia arising after delivery of metal-ceramic fixed dental prosthesis

Focal epithelial hyperplasia (FEH) is a human papillomavirus (HPV)-induced alteration of the oral mucosa that presents with a clinically distinct appearance. While other HPV-infected lesions such as squamous papilloma, verruca vulgaris, and condyloma acuminatum involve the skin, oral mucosa, and genital mucosa, FEH occurs only in the oral mucosa. The affected oral mucosa exhibits multiple papules and nodules with each papule/nodule being flat-topped or sessile. The affected region resembles the normal color of oral mucosa rather than appearing as a white color since the epithelial surface is not hyperkeratinized. Almost all cases present with multiple sites of occurrence. This rare, benign epithelial proliferation is related to low-risk HPV, especially HPV-13 and -32, and is not transformed into carcinoma. We report a case of FEH that arose on the attached gingiva of an East Asian male adult related to prosthesis without detection of any HPV subtype in HPV DNA chip and sequencing.

Comparative Evaluation of the HPV28 Detection and HPV DNA Chip Test for Detecting and Genotyping Human Papillomaviruses

BACKGROUND: The HPV28 Detection test (Seegene) is a real-time polymerase chain reaction assay that is designed for testing a total of 28 human papillomavirus (HPV) genotypes and estimating the approximate HPV viral load. The aim of this study was to evaluate the clinical applicability of the HPV28 Detection test with regard to the prevalence of HPV infection and distribution of HPV genotypes by using the HPV28 Detection and HPV DNA Chip tests (Biomedlab). METHODS: HPV DNA Chip and HPV28 Detection tests were performed for 500 cervical swab specimens. HPV genotype results were confirmed by sequencing analysis of the specimens that showed discordant results in the 2 test methods. RESULTS: The positive rate of HPV detection determined by using HPV28 Detection and HPV DNA Chip tests were 43.8% and 40.6%, respectively. The sequencing results in 64 discordant specimens that showed single HPV infection in the 2 test methods were in complete agreement with the test results obtained with the HPV28 Detection test. The genotyping results of the HPV28 Detection test were 100% concordant in repeated experiments with HPV-infected specimens that have 12 different HPV genotypes, i.e., types 16, 31, 33, 39, 42, 51, 52, 53, 58, 66, 68, and 70. The HPV28 Detection test was 100-fold more sensitive than the HPV DNA Chip test with serially diluted HPV DNAs. CONCLUSIONS: The HPV28 Detection test can be applied in the clinical field as an HPV genotyping test can accurately identify various HPV genotypes with high specificity and low detection limit.

Application of two methods of high-risk HPV detection in early screening of uterine cervical cancer / 中国肿瘤临床

Objective:This study aims to select the more suitable testing method for early screening of uterine cervical cancer to protect susceptible populations. Application value was compared between the two methods of high-risk HPV detection in early screening of uterine cervical cancer. Methods:The two methods, namely, fluorescence quantitation polymerase chain reaction(PCR) and HC2-HPV-DNA, were used to detect the infection status of 13 high-risk HPV types during women's health examination. The examined women were divided into four groups according to age (23 to 29 years old, 30 to 39 years old, 40 to 49 years old, and 50 to 58 years old). Statistical methods were applied to analyze the results. Results:The detected positive rates by fluorescence quantitation PCR and HC2-HPV-DNA were 15.93%(140/879) and 11.83%(104/879), respectively, among the 879 examined women. The common positive and negative rates were 9.56%(84/879) and 81.80%(719/879), respectively. The results of the two methods showed that the infection positive rate was obviously higher in the 40 to 49 year old and 50 to 58 year old groups. Statistical difference was observed between fluorescence quantitation PCR and HC2-HPV-DNA in detecting high-risk HPV types (P40 years old who are at high risk of HPV, to prevent uterine cervical cancer efficiently.

Avaliação de métodos diagnósticos, morfológicos e biomoleculares em mulheres encaminhadas com citologia alterada / The diagnostic efficacy of morphologic and molecular methods in women with abnormal citology

Introdução: o câncer do colo uterino é a neoplasia mais frequente em mulheres de países em desenvolvimento. Doença causada pela infecção persistente com diferentes tipos de papilomavírus humano (HPV) classificados em baixo e alto risco, de acordo com o potencial oncogênico. Objetivo: em mulheres com diagnóstico citopatológico anormal por ocasião de exame de rastreamento do câncer cervical, encaminhadas por diferentes postos de atendimento do Sistema Único de Saúde para serviço universitário de referência e com diagnóstico definitivo de lesão intraepitelial de alto grau ou câncer cervical, avaliara eficácia diagnóstica de métodos morfológicos e biomoleculares utilizados de maneira isolada ou em associação; e a prevalência, estratificada em duasfaixas etárias, abaixo de 30 e igual ou superior a 30 anos, do HPV tipos 16, 18 e 45. Métodos: estudaram-se 167 mulheres encaminhadas ao Ambulatório de Patologia Cervical e Colposcopia do Hospital Universitário da Universidade Federal de Juiz de Fora, no período de novembro de 2002 e dezembro de 2003,com colo uterino íntegro, não grávidas e sem história de câncer no trato genital inferior. Coletaram-se, de todas as mulheres, amostras para estudo citológico,convencional e em meio líquido, e para os testes de DNA-HPV. Considerou-se como diagnóstico histopatológico final a avaliação mais grave dentre ospossíveis espécimes, biópsia, conização ou peça cirúrgica, que a paciente pudesse ter. Resultados: não há qualquer diferença no tocante à sensibilidade,ao valor preditivo positivo e negativo e à acurácia dentre os métodos diagnósticos estudados, porém a associação da citologia com o teste DNA-HPV tem menor especificidade que o exame citológico isolado, quer convencional ou em meio líquido. A prevalência do HPV 16, 18 e 45 cai de 88,9% para 50,0%nas mulheres com 30 anos ou mais (p = 0,02). Conclusão: nas mulheres encaminhadas ao ambulatório de PTGIC do HU-UFJF com colpocitologia alteradanão se justifica a realização de qualquer exame confirmatório, devendo realizar-se imediatamente a colposcopia para se ter o desfecho diagnóstico.

Introduction: cervical cancer is the most frequent neoplasia among the women of countries in development. Great part of these cases is caused by persistent infection with different types of human papilomavirus (HPV) classified as low and high risk, according to the risk of cervical cancer development. Objectives:based on women with abnormal cytology when screening for cervical cancer who were led from different units of the Public Health System to the reference university service and with a definite diagnosis of high cervical intraepithelial neoplasia or cancer, was to evaluate the diagnostic efficacy of morphologicand molecular methods used alone or together and the prevalence of HPV types 16, 18, 45, stratified into two age brackets. Methods: 167 women went to the Cervical Pathology and colposcopy clinic of the University Hospital of the Universidade Federal de Juiz de Fora, during the period from November 2002 to December 2003, with intact uterine cervix, not pregnant and without previous chemical and/or radiotherapy treatment for the inferior genital tract.Samples for cytology study were collected from all women, with conventional and liquid-based preparations, for CH2 for high risk virus, for DNA PAP andfor Probe Pack test. The worst histologic diagnosis among the possible histologic studies through biopsy, conization or cirurgic pieces was considered as "gold standard". Results: there is no difference regarding sensibility, positive predict value and negative predict value for all methods studied, However, the DNA PAP method has less specificities than the citology exam, either with conventional or based-liquid preparation. The prevalence of HPV 16, 18, 45 decreases from 88,9% to 50% in women of 30 years old or more, being this decrease statistically significant. Conclusion: in those women led to the PTGIC of the HUUFJF with abnormal cytology it is not necessary to repeat any tests, just colposcopy in order to reach the final diagnosis.

Demographic characteristics, risk factors and immunocytochemistry of p16INK4a, Ki-67, MCM5, and survivin as predictors for the progress of cervical precancer lesion.

Aim To identify the predictive factors and biomarkers in the progression of cervical precancer lesion or Cervical Intraepithelial Neoplasia (CIN). Methods The study was conducted from August 2007 to September 2008. Design of the study was case-control with stratifications of test dose response. The cases were patients with CIN. Control patients were non CIN patients. Bivariate analysis followed by multivariate analysis was conducted. Results There were 130 patients, consisting of 124 CIN patients divided into CIN 1, CIN 2 and CIN 3, with the following numbers of patients: 30, 41, and 33, respectively and 26 patients without CIN (non CIN). Bivariate analysis showed that age < 41 years, education ≥ 13 years, sexual partner ≥ 2, first sexual relationship at age < 22 years, smoking, the presence of sexuallly transmitted infections, positive HPV DNA, high p16INK4a, Ki-67, MCM5 and Survivin expression constituted independent variables for the occurrence of CIN with P value of < 0.05. However, on multivariate analysis, independent variables that emerged were age, education ≥ 13 years, sexual partner ≥ 2 persons, positive HPV DNA, and over expression of p16INK4a, Ki-67 and Survivin that showed a P value of < 0.005. Conclusion Younger ages, education age ≥ 13 years, sexual partner ≥ 2 persons, positive HPV DNA, high p16INK4a, Ki-67 and Survivin expression constituted the risk factors for the occurrence of the progress of CIN, and was used in the equation to predict the progress of cervical precancer lesion.

Detection of human papillomavirus type 16 and 18 by PCR in patients with cervical neoplasia / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to evaluate the detection rate of human papillomavirus (HPV) DNA Test (type 16 and 18) and to investigate the clinical significance of HPV DNA test in patients with cervical neoplasia. METHODS: Of the 708 patients aged 21~83 years who had undergone both conventional Papanicolaou cervical cytologic test and HPV DNA test by polymerase chain reaction, 383 cases underwent histologic diagnoses. RESULTS: Of the 708 cytologic diagnoses, there were 11 positive HPV DNA test diagnoses in squamous cell carcinoma (SCC), 41 in high-grade squamous intraepithelial lesion (HSIL), 20 in low-grade squamous intraepithelial lesion (LSIL), 41 in atypical squamous cells (ASC), and 86 in negative cytology. Of the 383 histologic diagnoses, there were 24 positive HPV DNA test diagnoses in SCC, 42 in cervical intraepithelial neoplasia (CIN) 3, 12 in CIN 2, 12 in CIN 1, 7 in atypical change, and 45 in negative histology. Of the 239 patients with negative HPV DNA test, 28.5% cases showed histologic diagnoses of CIN 1 or worse lesion. Of the 46 patients with negative cytology and positive HPV DNA test, 50.0% cases showed histologic dianoses of CIN 1 or worse lesion. Pap cytology revealed sensitivity of 72.5%, specificity of 66.4%, and false negative rate of 27.5%, whereas HPV DNA test showed 57.5%, 76.7%, and 42.5%, respectively. CONCLUSION: This study confirmed that the primary standard Pap cytology and HPV DNA test were adjunctive. Also this study showed that physicians always should not overrate Pap cytology or HPV DNA test in managing the patient with cervical neoplasia. Combined test was a very effective diagnostic method for detecting cervical neoplasia.

Human papillomavirus infection (HPV) & screening strategies for cervical cancer.

The incidence of cervical cancer is declining slowly necessitating concerted and organized control measures. Control through primary prevention has become a distinct reality though a prophylactic vaccine, which may take quite some time for its widespread use. Thus control of cervical cancer through secondary preventive measures is the only viable solution now. While high quality cytology screening may not be feasible for widescale implementation in developing countries because of lack of necessary infrastructure, quality control and poor sensitivity of cytology, alternative screening modalities such as visual screening techniques and HPV-DNA can be explored. Some technical and feasibility aspects of these three modalities are discussed.

Promoter methylation of APC genes in cervical cancer: correlation with clinicopathologic characteristics / 中国癌症杂志

Background and purpose: The Writ cell-signaling pathway is the key cellular developmental pathway. Dysregulation of this pathway has been implicated in the initiation and progression of cancer. Adenomatous polyposis coli (APC) is an important tumor suppressor gene of the Writ signaling pathway. The methylation of APC promoter and the accompanying loss of the APC transcript have been shown to occur in a significant proportion of cancers. However, there are few reports on the relationship between cervical cancer and methylation of APC. This study was aimed to investigate the promoter methylation status of the APC genes in cervical cancer and its correlation between clinicopathologic characteristics and the infection of high-risk HPV DNA. Methods: Promoter methylation was evaluated using a MSP (methylation-specific polymerase chain reaction) in 95 cervical cancer tissue specimens and 20 normal controls. The relationship between clinicopathologic parameters and the methylation status was evaluated. Results: The frequencies of promoter methylation of APC in cervical cancer were 56.8%. Cervical cancer had significant higher methylation frequencies than that of the controls (10%, P<0.01). The result showed that the methylation analysis of APC promoter and high-risk HPV DNA testing had good consistency (Kappa=0.348, P<0.001). The promoter methylation of APC was significantly higher in adenocarcinoma (AC) than in squamous cell carcinoma (SCC) (74.1% vs 50.0%, respectively, P<0.05). The larger tumor size, positive lymph node metastasis and positive HPV DNA exhibited an increased promoter methylation frequency for APC (P<0.05). There were no significant associations between the methylation frequencies for APC gene to age, invasion depth, FIGO stage and histological grade. Conclusion: Our results suggested that the promoter methyiation of APC and high-risk HPV DNA testing had good consistency. APC gene promoter methylation was a frequent epigenetic event in cervical carcinoma and had a significant correlation with cancer pathological types.

Detection of HPV Genotypes in Non-genital SeborrheicKeratosis by HPV DNA Chip Analysis / 대한피부과학회지

BACKGROUND: The precise etiology of seborrheic keratosis (SK) is unknown. Genetics, sun exposure and infection have all been implicated as possible factors. Because of its clinical and histopathological similarities to verrucae vulgaris and condyloma acuminatum, human papillomavirus (HPV) has been suggested as a possible causative agent. In the previous studies, HPV were frequently detected in the genital lesions or hair follicles of immunocompromised hosts. OBJECTIVE: A newly introduced HPV detection technique, the HPV DNA Chip analysis, contains 24 HPV probes and it has the advantage of being able to detect 24 types of HPV at once. The purpose of this study was to evaluate the presence of HPV DNA in the nongenital SK of immunocompetant individuals. METHODS: We analyzed 31 biopsy specimens that were taken from patients with nongenital SK, and these specimens were compared with genital warts (the positive control) and distilled water in place of DNA (the negative control) with using HPV DNA Chip analysis and a polymerase chain reaction-based DNA microarray system as the HPV genotyping method. RESULTS: By polymerase chain reaction (PCR), HPV DNA was detected in 2 of the 31 nongenital SK biopsies (6.5%). HPV DNA Chip analysis revealed that 3 of 31 nongenital SKs (9.7%) contained HPV DNA. Two distinct HPV genotypes were detected: HPV type 16 (n=2) and HPV type 42 (n=1). The duration of SK in the HPV positive group was longer than that of the SK in the negative group. The mean age of the patients in the HPV positive group was also older than the mean age of the negative group. There were no different histopathologic findings between the HPV positive and negative SK. CONCLUSION: This study did not provide any concrete evidence that HPV infection might directly play a part in the pathogenesis of nongenital SK. However, two distinct HPV DNA types were identified as types that have never been reported before. Further studies with a larger number of cases of SK are needed to confirm the presence of HPV DNA in nongenital SK and also to determine the role of HPV in the origin of nongenital SK.