[Clinicopathological characteristics of HPV(+) oropharyngeal squamous cell carcinoma].

Objective: To observe the clinicopathologic features of oropharyngeal squamous cell carcinoma associated with human papilloma virus (OPSCC-HPV) and discuss the role and value of different in situ hybridization (ISH) detection methods for HPV in pathologic diagnosis. Methods: Fifteen cases of OPSCC-HPV were collected from Department of Pathology, Beijing Tongren Hospital, Capital Medical University from January 2016 to August 2018. These cases were diagnosed in accordance with the WHO classification of head and neck tumors. The histopathologic features and the clinicopathologic data were retrospectively analyzed. Immunohistochemistry (two-step EnVision method) was done to evaluate the expression of p16, Ki-67 and p53. ISH was used to detect HPV DNA (6/11 and 16/18). RNAscope technology was used to evaluate the presence of HPV mRNAs (16 and 18). Results: The mean age for the 15 patients (8 males, 7 females) was 47 years (range from 30 to 69 years). OPSCC-HPV typically presentedat an advanced clinical stage, six patients had cervical lymphadenopathy (large and cystic), seven had tonsillar swelling, one had tumor at base of tongue, and one had odynophagia. Microscopically the tumors exhibited distinctive non-keratinizing squamous cell carcinoma morphology. Cervical nodal metastases were large and cystic, with thickening of lymph node capsules. OPSCC-HPV raised from crypt epithelium and extended beneath the tonsillar surface epithelial lining as nests and lobules, often with central necrosis. Tumor cells displayed a high N: C ratio, and high mitotic and apoptotic rates. Tumor nests are often embedded within lymphoid stroma, and may be infiltrated by lymphoid cells.Fifteen cases (15/15) were strongly positive for p16; Ki-67 index were 60%-90%; they were focally positive or negative for p53. Ten cases (10/10) were negative for HPV 6/11 DNA, and one case(1/10) was focally positive for HPV16/18 DNA. Eleven cases (11/11) were strongly positive for HPV16 mRNA, one case was focally positive for HPV18 mRNA. Conclusions: OPSCC-HPV is a pathologically and clinically distinct form of head and neck squamous cell carcinoma. OPSCC-HPV is associated with high-risk HPV (type 16) in all cases. Detection of high-risk HPV16 mRNA by RNAscope is of great significance in the final diagnosis and pathogen identification.

Clinicopathological characteristics of HPV+ oropharyngeal squamous cell carcinoma / 中华病理学杂志

Objective@#To observe the clinicopathologic features of oropharyngeal squamous cell carcinoma associated with human papilloma virus (OPSCC-HPV) and discuss the role and value of different in situ hybridization (ISH) detection methods for HPV in pathologic diagnosis.@*Methods@#Fifteen cases of OPSCC-HPV were collected from Department of Pathology, Beijing Tongren Hospital, Capital Medical University from January 2016 to August 2018. These cases were diagnosed in accordance with the WHO classification of head and neck tumors. The histopathologic features and the clinicopathologic data were retrospectively analyzed. Immunohistochemistry (two-step EnVision method) was done to evaluate the expression of p16, Ki-67 and p53. ISH was used to detect HPV DNA (6/11 and 16/18). RNAscope technology was used to evaluate the presence of HPV mRNAs (16 and 18).@*Results@#The mean age for the 15 patients (8 males, 7 females) was 47 years (range from 30 to 69 years). OPSCC-HPV typically presentedat an advanced clinical stage, six patients had cervical lymphadenopathy (large and cystic), seven had tonsillar swelling, one had tumor at base of tongue, and one had odynophagia. Microscopically the tumors exhibited distinctive non-keratinizing squamous cell carcinoma morphology. Cervical nodal metastases were large and cystic, with thickening of lymph node capsules. OPSCC-HPV raised from crypt epithelium and extended beneath the tonsillar surface epithelial lining as nests and lobules, often with central necrosis. Tumor cells displayed a high N: C ratio, and high mitotic and apoptotic rates. Tumor nests are often embedded within lymphoid stroma, and may be infiltrated by lymphoid cells.Fifteen cases (15/15) were strongly positive for p16; Ki-67 index were 60%-90%; they were focally positive or negative for p53. Ten cases (10/10) were negative for HPV 6/11 DNA, and one case(1/10) was focally positive for HPV16/18 DNA. Eleven cases (11/11) were strongly positive for HPV16 mRNA, one case was focally positive for HPV18 mRNA.@*Conclusions@#OPSCC-HPV is a pathologically and clinically distinct form of head and neck squamous cell carcinoma. OPSCC-HPV is associated with high-risk HPV (type 16) in all cases. Detection of high-risk HPV16 mRNA by RNAscope is of great significance in the final diagnosis and pathogen identification.

Use of HPV testing in cervical cancer screening services in Mexico, 2008-2018: a nationwide database study / Uso de la prueba de VPH para la detección de cáncer cervical en México, 2008-2018: estudio de una base de datos nacional

Abstract: Objective: To describe the methods of a study aimed at evaluating high risk-HPV (hrHPV)-based screening and cervical cytology as triage compared to conventional cervical cytology as primary screening in the detection of grade 2+ cervical intraepithelial neoplasia in the National Cancer Screening Program (NCSP) of Mexico. Materials and methods: We will use information originated from the Womens Cancer Information System of Mexico regarding cervical cancer from 2008 to 2018. The database includes cytology results, diagnostic confirmation by histopathology and/or treatment colposcopy. We will then carry out statistical analyses on approximately 15 million hrHPV. Results: We will evaluate the overall performance of hrHPV-based screening as part of the NCSP and compare hrHPV-based to cytology-based screening under real-life conditions. To guarantee an unbiased comparison between hrHPV with cytology triage and conventional cytology we will use propensity score matching. Conclusion: Decision makers may use our results to identify areas of opportunity for improvement in NCSP processes.

Resumen: Objetivo: Describir los métodos de un estudio que busca comparar el beneficio de la introducción de la prueba de VPH de alto riesgo como prueba primaria frente a la citología convencional para la detección de la neoplasia intraepitelial cervical grado 2 o mayor, dentro del Programa de Prevención y Control del Cáncer de la Mujer, para el periodo de 2008 a 2018. Material y métodos: Se utilizarán los registros del Sistema de Información de Cáncer de la Mujer, se realizarán los análisis estadísticos con aproximadamente 15 millones de resultados de VPH-alto riesgo, además se utilizarán los resultados de citología, colposcopia, histología y los casos referenciados al centro oncológico para tratamiento. Para comparar ambos grupos usaremos "propensity score matching". Resultados: Se evaluará el desempeño general de la prueba de VPH-alto riesgo, en condiciones reales dentro del Programa Nacional de Prevención y Control de la Mujer y su tendencia en el tiempo. Conclusiones: Los resultados de estudio ayudarán a los tomadores de decisiones a identificar áreas de oportunidad para mejorar el programa en México.

High-risk mucosal HPV types associated with squamous cell carcinoma on the nose tip in an immunocompetent young man

Abstract: The oncogenic role of high-risk HPV in anogenital, head and neck, and cervical cancer is well recognized, but not in skin cancer in the general population. Some authors have demonstrated their appearance mainly on the hands and feet, particularly in the area of the nail bed, which could be due to contamination with HPV types from anogenital regions. Here, we describe a case of genital HPV associated with SCC on the nose tip in an immunocompetent young man, which was confirmed by histopathological findings and in situ hybridization. The importance of this report is to highlight the potential role of HPV in the etiology of skin cancer in an immunocompetent individual.

[Significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma of the larynx].

Objective: To study the significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma (BSCC) of the larynx. Methods: Twenty-nine cases of laryngeal BSCC from Beijing Tongren Hospital from January 2005 to December 2011 were reviewed. HPV typing by polymerase chain reaction-reverse dot blot (PCR-RDB) and p53, Ki-67, p16, p21 and cyclin D1 expression by immunohistochemistry were performed. The relationship between these indicators, various pathologic parameters (TNM, tumor size, tumor site and lymph node metastasis) and HPV status was analyzed. Results: There were 27 male and 2 female patients. The median age was 62 years. Lymph node metastasis and supraglottic tumor location were slightly higher than that of "usual" SCC, but not statistically significant (P>0.05). HPV DNA was detected in 27.6% (8/29) of the laryngeal BSCC, and all were HPV16. The expression of HPV was not related to age, alcohol consumption, tumor stage and tumor size. p53 was expressed in 31.0%(9/29) of laryngeal BSCC, and these cases were more likely supraglottic and had lymph node metastases (P<0.05). p16 staining was seen in 24.1% (7/29) of laryngeal BSCC, and these cases showed slightly higher rate of lymph node metastasis compared to p16 negative cases. The expression rates of p21 and cyclinD1 were 27.6% (8/29) and 69.0%(20/29), respectively, which were not related to age, tumor size, stage, lymph node metastasis, smoking and drinking. There were only 3 p16+ /HPV+ cases, which showed higher p21 and Ki-67 index compared to the HPV negative group (P<0.05). Conclusion: Some laryngeal BSCC expresses HPV DNA, possibly indicating an association with HPV; but p16 expression is not a reliable indicator for HPV infection.

Significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma of the larynx / 中华病理学杂志

Objective@#To study the significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma (BSCC) of the larynx.@*Methods@#Twenty-nine cases of laryngeal BSCC from Beijing Tongren Hospital from January 2005 to December 2011 were reviewed. HPV typing by polymerase chain reaction-reverse dot blot (PCR-RDB) and p53, Ki-67, p16, p21 and cyclin D1 expression by immunohistochemistry were performed. The relationship between these indicators, various pathologic parameters (TNM, tumor size, tumor site and lymph node metastasis) and HPV status was analyzed.@*Results@#There were 27 male and 2 female patients. The median age was 62 years. Lymph node metastasis and supraglottic tumor location were slightly higher than that of "usual" SCC, but not statistically significant (P>0.05). HPV DNA was detected in 27.6% (8/29) of the laryngeal BSCC, and all were HPV16. The expression of HPV was not related to age, alcohol consumption, tumor stage and tumor size. p53 was expressed in 31.0%(9/29) of laryngeal BSCC, and these cases were more likely supraglottic and had lymph node metastases (P<0.05). p16 staining was seen in 24.1% (7/29) of laryngeal BSCC, and these cases showed slightly higher rate of lymph node metastasis compared to p16 negative cases. The expression rates of p21 and cyclinD1 were 27.6% (8/29) and 69.0%(20/29), respectively, which were not related to age, tumor size, stage, lymph node metastasis, smoking and drinking. There were only 3 p16+ /HPV+ cases, which showed higher p21 and Ki-67 index compared to the HPV negative group (P<0.05).@*Conclusion@#Some laryngeal BSCC expresses HPV DNA, possibly indicating an association with HPV; but p16 expression is not a reliable indicator for HPV infection.

Achados citológicos em pacientes com captura híbrida positiva para papilomavírus humano em um laboratório de patologia de Criciúma / Citologic findings in patients with positive hybrid capture for human papillomavirus in a pathology laboratory in Criciúma

A infecção pelo HPV é a infecção sexualmente transmissível mais comum no mundo e está intimamente relacionada ao câncer de colo uterino. Acomete mulheres jovens sexualmente ativas com incidência de aproximadamente 25 a 45%. O objetivo do trabalho é conhecer os achados citológicos em pacientes com captura híbrida positiva para Papilomavírus humano em um laboratório de patologia de Criciúma, no período de junho de 2010 a maio de 2013. Foi realizado um estudo censitário, descritivo, observacional, transversal e quantitativo. A amostra foi composta por 75 mulheres com captura híbrida positiva para Papilomavírus humano e idade mediana de 27,0 anos (23,0 ­ 32,0). Observou-se que 96,0% (n=72) dos exames citopatológicos do colo uterino apresentaram resultado normal, enquanto 4,0% (n=3) demonstraram lesão cervical de baixo grau. Em relação ao resultado do teste de captura híbrida, notou-se infecção pelo subtipo viral de alto risco oncogênico em 66,6% (n=50) das pacientes. Não houve significância estatística (p=0,253) entre as variáveis idade e os subtipos virais de HPV encontrados na captura híbrida. Pode-se identificar a concordância com a literatura no que se refere à idade de maior prevalência de infecção pelo HPV, a maior proporção de exames citopatológicos normais dentre os infectados e o maior número de infecções por HPV de alto risco oncogênico. Nossos achados podem contribuir para futuros estudos visando avaliar o benefício custo-efetivo do teste de captura híbrida como método de rastreamento populacional do câncer de colo uterino.

The HPV infection is the most common sexually transmitted infection in the world and is closely related to cervical cancer. It affects young women who are sexually active with incidence of approximately 25-45 %. The objective is discover the cytological findings in patients with positive hybrid capture for human papillomavirus in a pathology laboratory in Criciuma, from the time period of June 2010 to May 2013. A census-based study, descriptive, observational, cross-sectional and quantitative. The sample consisted of 75 women with positive HPV hybrid capture and who are around the age of 27, 0 years old (23.0 to 32.0). It was observed that 96.0% (n = 72) of cervical screening showed normal results, while the other 4.0%(n = 3) demonstrated low-grade cervical lesion. In relation to the results of the hybrid capture test, it was noticed that infection by high- risk viral subtype HPV in 66.6% (n =50) of patients. There was no statistically breadth of significance (p = 0.253) between the variable age and subtypes of HPV found in the hybrid capture. You can identify the agreement with the literature as regards to the age of highest prevalence of HPV infection, the largest proportion of normal Pap smears from the infected and the largest number of infections by high oncogênico risk HPV. Our findings may contribute to future studies to evaluate the benefits of costeffective hybrid capture test as a method of populational screening of cervical cancer.

[Influence of Age in the Prevalence of High-Risk Human Papiloma Virus in Women with Pre-Neoplasic Cervical Lesions in Navarra, Spain]. / Influencia de la edad en la prevalencia de virus de papiloma humano de alto riesgo en mujeres con lesiones precursoras de cáncer de cuello uterino en la Comunidad Navarra.

OBJECTIVE: Cervical carcinoma (CC) is the second cause of death among women aged 15 and 44 in Spain. CC is linked to hig-risk human papillomavirus (HR-HPV) infection and its prevalence varies according age and geographical region. The awereness of the latter is essential for public health prevention efforts. The aim was to study the age related in HR-HPV genotypes in cytologies with squamous intraepithelial lesion (SIL). METHODS: From a total of 67,935 ginecologic cytologies over a four-year period, we selected cytologic specimens with SIL. We used the Cervista® test to detect HR-HPV DNA. Women were classified into two groups under 35 and over 35 years old. Proportions were estimated with confidence intervals at 95% (95% CI). RESULTS: HR-HPV prevalence was 59,7%; 64,6% in women under 35 years old. HR-HPV species alpha 9 type 16 (HR-HPV 16) and alpha 5 type 51 (HR-HPV 51) were the most prevalent (60,9% and 51,7%). High-grade squamous intraepithelial lesions (H-SIL) were twice as high in women under 35 years (6,5 vs. 3,7%). 88,8% of H-SIL was associated HR-HPV 16, which increases the probability of H-SIL against Low-grade squamous intraepithelial lesions (L-SIL) regardless of age. CONCLUSIONS: In our population HR-HPV 16 was associated to H-SIL whereas HR-HPV specie alpha 7 type 18 and HR-HPV 51 to L-SIL regardless of age. The high prevalence of HR-HPV 51 in Navrra´s population (51,7%), suggests that local vaccination programs be re-assessed.

El cáncer de cuello uterino (CCU)es la segunda causa de muerte en España en mujeres entre 15 y 44 años. Esta ligado íntimamente a la infección por el virus del papiloma humano de alto riesgo (VPH-AR). La prevalencia del VPH-AR incrementa según la gravedad de la lesión, grupo etario y región geográfica cuyo conocimiento es esencial para el desarrollo de estrategias de prevención. El objetivo fue determinar la influencia de la edad de las mujeres (menores o mayores de 35 años) en relación con la especie de VPH-AR presente y la lesión escamosa intraepitelial (LEI).

Examen de detección de virus papiloma humano en el tamizaje de cáncer cervicouterino en un Servicio de Salud de Santiago, Chile / Human papillomavirus testing in cervical cancer screening at a public health service of Santiago, Chile

Background: Molecular techniques for human papillomavirus (HPV) detection have a good performance as screening tests and could be included in cervical cancer early detection programs. We conducted a population-based trial comparing HPV detection and Papanicolaou as primary screening tests, in a public health service in Santiago, Chile. Aim: To describe the experience of implementing this new molecular test and present the main results of the study. Material and Methods: Women aged 25 to 64 enrolled in three public health centers were invited to participate. In all women, samples were collected for Papanicolaou and HPV DNA testing, and naked-eye visual inspection of the cervix with acetic acid was performed. Women with any positive screening test were referred to the local area hospital for diagnostic confirmation with colposcopy and biopsy of suspicious lesions. Results: Screening results were obtained for 8265 women, of whom 931 (11.3%) were positive to any test. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6) respectively. Conclusion: This experience showed that the implementation of a molecular test for cervical cancer screening is not a major challenge in Chile: it was well accepted by both the health team and the participants, and it may improve the effectiveness of the screening program.

Elucidating Molecular Interactions of Natural Inhibitors with HPV-16 E6 Oncoprotein through Docking Analysis.

Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The life-threatening infection caused by HPV demands the need for designing anticancerous drugs. In the recent years, different compounds from natural origins, such as carrageenan, curcumin, epigallocatechin gallate, indole-3-carbinol, jaceosidin, and withaferin, have been used as a hopeful source of anticancer therapy. These compounds have been shown to suppress HPV infection by different researchers. In the present study, we explored these natural inhibitors against E6 oncoprotein of high-risk HPV-16, which is known to inactivate the p53 tumor suppressor protein. A robust homology model of HPV-16 E6 was built to anticipate the interaction mechanism of E6 oncoprotein with natural inhibitory molecules using a structure-based drug designing approach. Docking analysis showed the interaction of these natural compounds with the p53-binding site of E6 protein residues 113-122 (CQKPLCPEEK) and helped the restoration of p53 functioning. Docking analysis, besides helping in silico validation of natural compounds, also helps understand molecular mechanisms of protein-ligand interactions.

Detection of Salivary Human Papilloma Viruses 16 and 18 (HPV) in Smoker Men in an Iranian Population by PCR: A Pilot Study.

BACKGROUND: Human papilloma virus (HPV) infection of the oropharynx is acquired through a variety of sexual and social forms of transmission. Recent epidemiologic evidence has suggested that HPV may be an independent risk factor for oropharyngeal cancers, but risk factors for persistent HPV infection in the oropharynx are unknown. More evidence is needed regarding the prevalence of oral high-risk HPV among healthy smoker and nonsmoker adults. OBJECTIVES: The aim of this study was to compare salivary infection with human papilloma virus types 16 and 18 between smokers and nonsmokers. PATIENTS AND METHODS: A hundred healthy adult subjects were selected from Zahedan dental school for this pilot study. DNA was isolated from saliva samples and screened for high-risk HPV strains of HPV 16 and 18. Then, further processed using Real Time PCR for quantification and confirmation of sensitivity and specificity of the test. Data was analyzed by t-test. RESULTS: There were no high-risk types of virus in patients and no significant differences between the groups (P = 1). CONCLUSIONS: It seems that smoking cannot increase the prevalence of high risk HPV 16, 18 in saliva samples.

Elucidating Molecular Interactions of Natural Inhibitors with HPV-16 E6 Oncoprotein through Docking Analysis

Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The life-threatening infection caused by HPV demands the need for designing anticancerous drugs. In the recent years, different compounds from natural origins, such as carrageenan, curcumin, epigallocatechin gallate, indole-3-carbinol, jaceosidin, and withaferin, have been used as a hopeful source of anticancer therapy. These compounds have been shown to suppress HPV infection by different researchers. In the present study, we explored these natural inhibitors against E6 oncoprotein of high-risk HPV-16, which is known to inactivate the p53 tumor suppressor protein. A robust homology model of HPV-16 E6 was built to anticipate the interaction mechanism of E6 oncoprotein with natural inhibitory molecules using a structure-based drug designing approach. Docking analysis showed the interaction of these natural compounds with the p53-binding site of E6 protein residues 113-122 (CQKPLCPEEK) and helped the restoration of p53 functioning. Docking analysis, besides helping in silico validation of natural compounds, also helps understand molecular mechanisms of protein-ligand interactions.

Epidermodysplasia verruciformis in a young man with HIV since birth - case report / Epidermodisplasia verruciforme em um jovem com HIV desde o nascimento - relato de caso

Epidermodysplasia Verruciformis is a genodermatosis characterized by susceptibility to infection by specific HPV types (HPV 3/10 and beta-HPVs). It is considered to be the first model in human carcinogenesis induced by HPV. In this report we present a rare case of Epidermodysplasia Verruciformis associated with vertical transmission of HIV. Although most patients with HIV present infections by HPV virus, the frequency of Epidermodysplasia Verruciformis is no greater in patients with HIV because in EV there is a deficiency of specific cellular immunity to infection by some types of HPV, called HPV-related Epidermodysplasia Verruciformis.

A Epidermodisplasia Verruciforme é uma genodermatose que se caracteriza pela susceptibilidade à infecção por tipos específicos de HPV (HPVs 3 e 10 e os beta-HPVs) e é considerada o primeiro modelo no homem de carcinogênese induzida pelo HPV. Neste artigo apresenta-se um caso raro de Epidermodisplasia Verruciforme em um paciente com HIV desde o nascimento. Apesar dos doentes com HIV apresentarem mais infecções pelos vírus HPVs, existem poucos relatos na literatura de Epidermodisplasia Verruciforme no doente com HIV. Isso se explica, pois a Epidermodisplasia Verruciforme é consequência de uma deficiência celular específica à infecção por alguns tipos distintos de HPVs, ditos HPVs relacionados a Epidermodisplasia Verruciforme.

Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16(INK4a) Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma.

BACKGROUND: Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site. METHODS: We compared histologic findings, p16(INK4a) expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract. RESULTS: All five SCCs of cervical origin showed strong expression of p16(INK4a), whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA. CONCLUSIONS: Although a thorough histological examination is important, immunonegativity for p16(INK4a) and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract.

Effect of high risk human papillomavirus test in screening of the patients with ASCUS / 中国基层医药

Objective To explore the clinical value of high risk human papillomavirus(HR-HPV) test in shunting monitoring of atypical squamous cell of undetermined significance (ASCUS) and to seek the best treatment for patients with ASCUS.Methods 470 patients with ASCUS tested by TCT were given HR-HPV testing and biopsy under colposcopy.The clinical characteristics were analyzed.Results 470 cases of ASCUS contained a variety of cervical lesions:inflammation/acuminate accounted for 69.15％ (325/470),cervical intraepithelial neoplasia (CIN)accounted for 29.57％ (139/470),and invasive carcinoma accounted for 1.28％ (6/470).The positive rate of cervical pathological examination was 30.85％ (≥ CIN Ⅰ,145/470).The positive rate of HR-HPV was 50.43％(237/470).The detection rate of ≥CIN Ⅰ in HR-HPV positive group and negative group was 55.27％ (131/237)and 6.01％ (14/233),while the detection rate of ≥ CIN Ⅱ in HR-HPV positive group and negative group was 36.71％ (87/237) and 1.29％ (3/233).The differences were statistically significant(P ＜ 0.01).Incidence of ≥ CIN Ⅰ and invasive carcinoma in HR-HPV positive group was about 19.332 fold of that in HR-HPV negative group(95％ CI =10.632 ～ 35.152),while the incidence of ≥CIN Ⅱ and invasive carcinoma was about 44.467 fold of HR-HPV negative group (95％ CI =13.812 ～ 143.152).The detection sensitivity,specificity,positive predictive value,negative predictive value(NPV) of HR-HPV in the≥ CIN Ⅰ patients were 90.34％,67.38％,61.60％,93.99％.Those of ≥ CIN Ⅱ patients were 96.67％,60.53％,36.71％,98.71％.Conclusion ASCUS included partial CIN of high grades and cervical cancer,and the proportion of HPV infection is large,detection of high risk HPV-DNA is an effective shunting management method of ASCUS.

Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16INK4a Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma

BACKGROUND: Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site. METHODS: We compared histologic findings, p16INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract. RESULTS: All five SCCs of cervical origin showed strong expression of p16INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA. CONCLUSIONS: Although a thorough histological examination is important, immunonegativity for p16INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract.

Expression of CHOP in squamous tumor of the uterine cervix.

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection and abnormal p53 expression are closely involved in carcinogenesis of squamous cell carcinoma (SqCC) of uterine cervix. Recent studies have suggested that virus-induced endoplasmic reticulum (ER) stress modulates various cell survival and cell death signaling pathways. The C/EBP homologous protein (CHOP) is associated with ER stress-mediated apoptosis and is also involved in carcinogenesis of several human cancers. We hypothesized that CHOP is involved in the carcinogenesis of uterine cervical cancer in association with HR-HPV and/or p53. METHODS: Immunohistochemistry was used to analyze CHOP and p53 protein expression of tissue sections from 191 patients with invasive cancer or preinvasive lesions of the uterine cervix (61 cases of SqCC, 66 cases of cervical intraepithelial neoplasia [CIN] III, and 64 cases of CIN I). RESULTS: CHOP was expressed in 59.4% of CIN I, 48.5% of CIN III, and 70.5% of SqCC cases. It was also significantly more frequent in invasive SqCC than in preinvasive lesions (p=0.042). Moreover, CHOP expression significantly correlated with HR-HPV infection and p53 expression (p=0.009 and p=0.038, respectively). CONCLUSIONS: Our results suggest that CHOP is involved in the carcinogenesis of the uterine cervix SqCC via association with HR-HPV and p53.

Prevalence and risk factors for cervical intraepithelial neoplasia among HIV-infected women

OBJECTIVES: To evaluate the prevalence and the risk factors for cervical intraepithelial neoplasia (CIN) among HIV-infected women. METHODS: Cross-sectional study of 494 HIV-infected women in Brazil, between 1998 and 2008. Gynecologic exam was performed, and samples were collected for cervical cytology and for HPV DNA detection. Cervical biopsy was carried out when indicated. HPV infection, CD4 T-lymphocyte count and HIV viral load were compared with cervical histopathology. Univariate and multivariate statistical analyses were performed to evaluate the statistical association of several risk factors. RESULTS: CIN prevalence detected by histopathology was 23.4% (6% of CIN2/3 and 17.4% cases of CIN1). Multivariate analysis confirmed an independent association of CIN with CD4 T-lymphocyte count below 200 cells/mm³ (OR 5.0, 95% CI 2.5-10.1), with a positive detection of HPV DNA (OR 2.0, 95% CI 1.2-3.5), and with age < 34 years old (OR 1.5, 95% CI 1.0-2.4). HIV viral load and antiretroviral use were not independent risk factors for CIN. CONCLUSIONS: Severity of immunosupression, presence of HPV infection and younger age are strong predictors of CIN among HIV-infected women.

Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests / Métodos de triagem colposcópica para detecção de neoplasia intraepitelial cervical grau 3 após diagnóstico citopatológico de lesão intraepitelial escamosa de baixo grau: uma revisão sistemática de testes diagnósticos

CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6 percent to 12 percent. The HPV-DNA positivity rate ranged from 64 percent to 83 percent; sensitivity for CIN3 detection ranged from 95.2 percent to 100 percent; and specificity was available in two studies (27 percent and 52 percent). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33 percent and 90.8 percent); and specificity was available in one study (53 percent). CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.

CONTEXTO E OBJETIVO: O desempenho do teste de DNA-HPV (ácido desoxirribonucleico-papilomavírus humano) oncogênico estratificado por idade para triagem de lesão intraepitelial escamosa de baixo grau (LSIL) demanda investigação. O objetivo do estudo foi avaliar e comparar o desempenho, para detecção de neoplasia intraepitelial cervical (NIC3), do teste de DNA-HPV oncogênico e da citologia de repetição estratificados por idade (ponto de corte 35 anos), para triagem de LSIL. TIPO DE ESTUDO E LOCAL: Revisão sistemática da literatura. Foram identificados estudos em nove bases de dados eletrônicas e listas de referências dos artigos recuperados. MÉTODOS: Critérios de elegibilidade: citologia inicial LSIL, realização do teste de DNA-HPV oncogênico e da citologia de repetição e detecção de NIC3. A diretriz QUADAS (Quality Assessment of Diagnostic Accuracy Studies) foi utilizada para avaliação da qualidade. As informações foram sintetizadas qualitativamente. RESULTADOS: Dentre 7.776 estudos, 284 eram pertinentes ao tema e três atenderam aos critérios de elegibilidade. A prevalência de NIC3 apresentou variação entre 6 por cento e 12 por cento. A taxa de positividade do teste de DNA-HPV apresentou variação entre 64 por cento e 83 por cento; a sensibilidade para NIC3 apresentou variação entre 95,2 por cento e 100 por cento; a especificidade estava disponível em dois estudos (27 por cento e 52 por cento). A sensibilidade da citologia de repetição (ponto de corte ASCUS - células escamosas atípicas de significado indeterminado) estava disponível em dois estudos (33 por cento e 90,8 por cento); a especificidade estava disponível em um estudo (53 por cento). CONCLUSÕES: Não existem, atualmente, evidências científicas disponíveis para comprovar que, em mulheres com 35 anos ou mais e citologia LSIL, a triagem colposcópica com teste de DNA-HPV oncogênico apresenta melhor desempenho para detecção de NIC3 do que a repetição citológica.

Expression of CHOP in Squamous Tumor of the Uterine Cervix

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection and abnormal p53 expression are closely involved in carcinogenesis of squamous cell carcinoma (SqCC) of uterine cervix. Recent studies have suggested that virus-induced endoplasmic reticulum (ER) stress modulates various cell survival and cell death signaling pathways. The C/EBP homologous protein (CHOP) is associated with ER stress-mediated apoptosis and is also involved in carcinogenesis of several human cancers. We hypothesized that CHOP is involved in the carcinogenesis of uterine cervical cancer in association with HR-HPV and/or p53. METHODS: Immunohistochemistry was used to analyze CHOP and p53 protein expression of tissue sections from 191 patients with invasive cancer or preinvasive lesions of the uterine cervix (61 cases of SqCC, 66 cases of cervical intraepithelial neoplasia [CIN] III, and 64 cases of CIN I). RESULTS: CHOP was expressed in 59.4% of CIN I, 48.5% of CIN III, and 70.5% of SqCC cases. It was also significantly more frequent in invasive SqCC than in preinvasive lesions (p=0.042). Moreover, CHOP expression significantly correlated with HR-HPV infection and p53 expression (p=0.009 and p=0.038, respectively). CONCLUSIONS: Our results suggest that CHOP is involved in the carcinogenesis of the uterine cervix SqCC via association with HR-HPV and p53.