Performance of three colposcopic images for the identification of squamous and glandular cervical precursor neoplasias.

PURPOSE: To evaluate prevalence and diagnostic performance of three colposcopic images to diagnose squamous and glandular cervical precursor neoplasias. METHODS: Cross-sectional study, conducted through analysis of stored digital colposcopic images. To evaluate the diagnostic performance of three images, herein named grouped glands, aceto-white villi, and atypical vessels, for detection of adenocarcinoma in situ (AIS) and cervical squamous intraepithelial neoplasias (CIN) grades 2 and 3, calculations of sensitivity, specificity, accuracy, positive likelihood ratio, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were made, with their respective 95% confidence intervals. RESULTS: Grouped glands, aceto-white villi, and atypical vessels images had: prevalence of 21.3, 53.8, and 33.8% in patients with AIS, and 16.2, 19.5, and 9.3% in those with CIN 2 and 3; for the diagnosis of AIS, sensitivity of 21.3, 53.8, and 33.8%, specificity of 89.8, 95.2, and 94.9%, accuracy of 76.6, 87.2, and 83.1%, positive likelihood ratio of 2.1, 11.2, and 6.6, and AUC of 0.55, 0.74, and 0.64; for the diagnosis of CIN 2 and 3, sensitivity of 16.2, 19.5, and 9.3%, specificity of 89.8, 95.2, and 94.9%, accuracy of 39.4, 43.4, and 36.3%, positive likelihood ratio of 1.6, 4.1, and 1, 8, and AUC of 0.53, 0.57, and 0.52, respectively. CONCLUSION: Prevalence and accuracy of the three images were higher for the diagnosis of glandular than squamous cervical precursor neoplasias. Sensitivity, specificity, positive likelihood, and AUC of aceto-white villi and atypical vessels images were higher for the diagnosis of glandular than squamous cervical precursor neoplasias.

Detection of Human papillomavirus and the role of p16INK4a in colorectal carcinomas.

INTRODUCTION: Human papillomavirus (HPV) infection is associated with the development of anogenital and head and neck cancers. In recent years a potential role of HPV in colorectal cancer (CRC) has been suggested. OBJECTIVE: To investigate the presence of HPV in colorectal carcinomas and to study the role of p16INK4a as a marker of transcriptionally active HPV infection. In addition, to investigate the correlation between these findings and the CRC prognostic factors. METHODS: Case control study with 92 cases of colorectal cancers, 75 controls of normal tissue adjacent to the tumor, and 30 controls of precursor lesions, including polyps and colorectal adenomas. Paraffinized samples were used, HPV detection and genotyping were performed by PCR and reverse hybridization by using the INNO LIPA kit, with SPF10 plus primers. The expression of the p16INK4a protein was investigated using immunohistochemistry. Data analysis was performed using descriptive, univariate statistics and survival curves were calculated by using the Kaplan Meier and log-rank method. RESULTS: HPV was detected in 13% of the cases and the most prevalent genotype was HPV 16. HPV DNA was not detected in either control groups. The high expression of p16INK4a was observed in 30% of the cases, but it was not associated to the presence of HPV. The overall survival was 53.3% and was influenced by prognostic factors such as later stage, lymph node and distant metastasis. CONCLUSIONS: Based on these results, HPV is unlikely to be involved in colorectal carcinogenesis and p16INK4a expression is not a relevant marker of transcriptionally active HPV infection in CRC.

Human papillomavirus and Chlamydia trachomatis infections in adolescents and young women: Prevalence and risk factors.

BACKGROUND: The objective of this study was to estimate the prevalence of Human papillomavirus (HPV) genotypes and Chlamydia trachomatis (CT) infections among adolescents and young adult women and to identify the risk factors associated. METHODS: This study included 276 sexually active participants, classified as adolescents (15-19 years) and young adult women (20-24 years) that realized conventional cytology and were tested for 27 HPV genotypes and for CT. Bivariate and multivariate analyses were performed to evaluate the factors associated with both infections. RESULTS: The prevalence of HPV infection was 50.7% in adolescents and 43.0% in young adult women. The HPV-16 was the most prevalent (27.7%), followed by HPV-68 (6.9%), HPV-52 (6.2%), HPV-39 (4.6%), and HPV-73 (4.6%). The prevalence of CT infection was 11.5% among adolescents and 6.2% among young adult women. Cytological abnormalities were found in 14.2% among adolescents, of which 80.9% were positive for HPV and 10% of young adult women of which 84.6% were positive for HPV infection. HPV16 and HPV 68 were detected in 35.7% and 32.1% of cases with cytological abnormalities. Factors independently associated with HPV infection obtained by multivariate analysis were unmarried or divorced marital status and the presence of cytological abnormalities. The same variables were analyzed for the association with CT infection, and the association with cytological abnormalities remained significant. CONCLUSION: HPV and CT infections are very prevalent in adolescent and young adult women; these findings reinforce the need of early vaccination, prior to the onset of sexual activity, and justify implementation of molecular screening tests.

Performance of Conventional Cytology and Colposcopy for the Diagnosis of Cervical Squamous and Glandular Neoplasias.

OBJECTIVE: To estimate the cytological and colposcopic performances for the diagnosis of cervical neoplasias. METHODS: Cross-sectional retrospective study with data from patients' charts. The participants underwent colposcopy, guided biopsies, and excision when needed. The cytological and colposcopic categorization followed the Bethesda System and the international colposcopic terminologies. The cytology and colposcopy performances were evaluated by sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) analyses with 95% confidence interval (95% CI). RESULTS: From 1,571 participants, a total of 1,154 (73.4%) were diagnosed with cervical squamous intraepithelial neoplasia grade 2 or worse (CIN 2+), 114 (7.2%) with adenocarcinoma in situ or worse (AIS+), 615 (39.2%) presented atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion or worse (ASC-H+) cytology, and 934 (59.4%) presented major or suspicious for invasion colposcopic abnormalities. The SE, SP, PPV, and NPV of ASC-H+ for diagnoses of CIN 2+ and AIS+ were, respectively: 44% (95% CI: 41-47) and 72% (95% CI: 67-76), 79% (95% CI: 77-81) and 79% (95% CI: 75-83), 88% (95% CI: 87-90) and 55% (95% CI: 50-60), and 28% (95% CI: 26-31) and 88% (95% CI: 85-91). The SE, SP, PPV, and NPV of major or suspicious for invasion colposcopic abnormalities for diagnoses of CIN 2+ and AIS+ were, respectively: 62% (95% CI: 60-65) and 86% (95% CI: 83-89), 59% (95% CI: 57-62) and 59% (95% CI: 55-64), 85% (95% CI: 83-87) and 44% (95% CI: 40-49), and 29% (95% CI: 27-32) and 92% (95% CI: 89-94). CONCLUSION: The SE analyses results of ASC-H+ and major or suspicious for invasion colposcopic abnormalities were higher for diagnoses of glandular neoplasias. These results confirm the role of cytology in identifying women at risk who will have their final diagnoses settled by colposcopy and histology.

OBJETIVO: Estimar o desempenho da citologia e colposcopia no diagnóstico das neoplasias cervicais. MéTODOS: Estudo retrospectivo de corte transversal com dados coletados em prontuários. Foram incluídas participantes que foram submetidas a colposcopia, biópsia e excisão quando necessário. A categorização da citologia e da colposcopia seguiram a terminologia de Bethesda e a classificação colposcópica internacional. Os desempenhos da citologia e colposcopia foram avaliados por análises de sensibilidade (S), especificidade (E), valor preditivo positivo (VPP) e valor preditivo negativo (VPN), com intervalos de confiança de 95% (IC 95%). RESULTADOS: Das 1.571 participantes, um total de 1.154 (73,4%) foram diagnosticadas com neoplasia intraepitelial escamosa cervical de grau 2 ou mais grave (NIC 2+), 114 (7,2%) com adenocarcinoma in situ ou mais grave (AIS+), 615 (39,2%) apresentaram células escamosas atípicas de significado indeterminado, quando não se pode excluir lesão intraepitelial de alto grau ou mais grave (ASC-H+) e 934 (59,4%) tiveram achados colposcópicos maiores ou suspeitos de invasão. Os valores de S, E, VPP e VPN das ASC-H+ para o diagnóstico de NIC 2+ e AIS+ foram, respectivamente: 44% (IC 95%: 41­47) e 72% (IC 95%: 67­76), 79% (IC 95%: 77­81) e 79% (IC 95%: 75­83), 88% (IC 95%: 87­90) e 55% (IC 95%: 50­60) e 28% (IC 95%: 26­31) e 88% (IC 95%: 85­91). Os valores de S, E, VPP e VPN dos achados colposcópicos maiores ou suspeitos de invasão para o diagnóstico de NIC 2+ e AIS+ foram, respectivamente: 62% (IC 95%: 60­65) e 86% (IC 95%: 83­89), 59% (IC 95%: 57­62) e 59% (IC 95%: 55­64), 85% (IC 95%: 83­87) e 44% (IC 95%: 40­49) e 29% (IC 95%: 27­32) e 92% (IC 95%: 89­94). CONCLUSãO: Os resultados das análises de S de ASC-H+ e achados colposcópicos maiores ou suspeitos de invasão foram mais elevados para o diagnóstico das neoplasias glandulares. Esses resultados confirmam o papel da citologia na identificação de mulheres em risco que terão seus diagnósticos definidos por colposcopia e histologia.

Performance of conventional cytology and colposcopy for the diagnosis of cervical squamous and glandular neoplasias / Desempenho da citologia convencional e da colposcopia para o diagnóstico de neoplasias cervicais escamosas e glandulares

Abstract Objective To estimate the cytological and colposcopic performances for the diagnosis of cervical neoplasias. Methods Cross-sectional retrospective study with data from patients' charts. The participants underwent colposcopy, guided biopsies, and excision when needed. The cytological and colposcopic categorization followed the Bethesda System and the international colposcopic terminologies. The cytology and colposcopy performances were evaluated by sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) analyses with 95% confidence interval (95% CI). Results From 1,571 participants, a total of 1,154 (73.4%) were diagnosed with cervical squamous intraepithelial neoplasia grade 2 or worse (CIN 2+), 114 (7.2%) with adenocarcinoma in situ or worse (AIS+), 615 (39.2%) presented atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion or worse (ASC-H+) cytology, and 934 (59.4%) presented major or suspicious for invasion colposcopic abnormalities. The SE, SP, PPV, and NPV of ASC-H+ for diagnoses of CIN 2+ and AIS+ were, respectively: 44% (95% CI: 41-47) and 72% (95% CI: 67-76), 79% (95% CI: 77-81) and 79% (95% CI: 75-83), 88% (95% CI: 87-90) and 55% (95% CI: 50-60), and 28% (95% CI: 26-31) and 88% (95% CI: 85-91). The SE, SP, PPV, and NPV of major or suspicious for invasion colposcopic abnormalities for diagnoses of CIN 2+ and AIS+were, respectively: 62% (95% CI: 60-65) and 86% (95% CI: 83-89), 59% (95% CI: 57-62) and 59% (95% CI: 55-64), 85% (95% CI: 83-87) and 44% (95% CI: 40-49), and 29% (95% CI: 27-32) and 92% (95% CI: 89-94). Conclusion The SE analyses results of ASC-H+ and major or suspicious for invasion colposcopic abnormalities were higher for diagnoses of glandular neoplasias. These results confirm the role of cytology in identifying women at risk who will have their final diagnoses settled by colposcopy and histology.

Resumo Objetivo Estimar o desempenho da citologia e colposcopia no diagnóstico das neoplasias cervicais. Métodos Estudo retrospectivo de corte transversal com dados coletados em prontuários. Foram incluídas participantes que foram submetidas a colposcopia, biópsia e excisão quando necessário. A categorização da citologia e da colposcopia seguiram a terminologia de Bethesda e a classificação colposcópica internacional. Os desempenhos da citologia e colposcopia foram avaliados por análises de sensibilidade (S), especificidade (E), valor preditivo positivo (VPP) e valor preditivo negativo (VPN), com intervalos de confiança de 95% (IC 95%). Resultados Das 1.571 participantes, um total de 1.154 (73,4%) foram diagnosticadas com neoplasia intraepitelial escamosa cervical de grau 2 ou mais grave (NIC 2+), 114 (7,2%) com adenocarcinoma in situ ou mais grave (AIS+), 615 (39,2%) apresentaram células escamosas atípicas de significado indeterminado, quando não se pode excluir lesão intraepitelial de alto grau ou mais grave (ASC-H+) e 934 (59,4%) tiveram achados colposcópicos maiores ou suspeitos de invasão. Os valores de S, E, VPP e VPN das ASCH + para o diagnóstico de NIC 2+ e AIS+ foram, respectivamente: 44% (IC 95%: 41-47) e 72% (IC 95%: 67-76), 79% (IC 95%: 77-81) e 79% (IC 95%: 75-83), 88% (IC 95%: 87-90) e 55% (IC 95%: 50-60) e 28% (IC 95%: 26-31) e 88% (IC 95%: 85-91). Os valores de S, E, VPP e VPN dos achados colposcópicos maiores ou suspeitos de invasão para o diagnóstico de NIC 2+ e AIS+ foram, respectivamente: 62% (IC 95%: 60-65) e 86% (IC 95%: 83-89), 59% (IC 95%: 57-62) e 59% (IC 95%: 55-64), 85% (IC 95%: 83-87) e 44% (IC 95%: 40-49) e 29% (IC 95%: 27-32) e 92% (IC 95%: 89-94). Conclusão Os resultados das análises de S de ASC-H+ e achados colposcópicos maiores ou suspeitos de invasão foram mais elevados para o diagnóstico das neoplasias glandulares. Esses resultados confirmam o papel da citologia na identificação de mulheres em risco que terão seus diagnósticos definidos por colposcopia e histologia.

Association between the human papillomavirus, bacterial vaginosis and cervicitis and the detection of abnormalities in cervical smears from teenage girls and young women.

BACKGROUND: Human papillomavirus (HPV) infection, bacterial vaginosis (BV), and cervicitis may play a role in the presence of cytological abnormalities in female adolescents and young women. This study aimed to estimate the prevalence of HPV, BV and cervicitis in female adolescents and young women and evaluate whether these conditions are associated with a finding of cytological abnormalities in cervical smears. METHODS: Cervical smears were screened using the conventional method and HPV-DNA detection was performed by PGMY-PCR. BV was defined as ≥20% clue cells in cervical smears. Cervicitis was assessed by counting leukocytes in five non-adjacent microscopic fields at 1000× magnification. Odds ratios and 95% confidence intervals were calculated. RESULTS: The study analyzed 251 samples, with cytological abnormalities being found in 9.5% (24/251). Atypical squamous cells of undetermined significance (50.0%) and low-grade squamous intraepithelial lesions (29.1%) were the most common findings. HPV, BV and cervicitis were found in 44.2% (111/251), 41.0% (103/251) and 83.2% (209/251) of cases, respectively. Of the variables investigated, BV and an abnormal cytological diagnosis were independently associated with HPV positivity. Cytological abnormalities were significantly associated with a finding of HPV and BV in the same woman, and also with a simultaneous finding of HPV, BV and cervicitis; however, the independent association of these combined variables did not remain significant in the multivariate analysis. CONCLUSIONS: BV and cytological abnormalities were independently associated with HPV infection in female adolescents and young women.

Prevalência da infecção pelo HPV em cânceres não anogenitais: uma revisão sistemática / Prevalence of HPV infection in non-anogenital cancers: a systematic review

O papilomavírus humano (HPV), uma das infecções sexualmente transmissíveis mais comuns no mundo, tem um papel estabelecido na patogênese de cânceres genitais, bem como no câncer anal. Essa infecção também foi implicada na oncogênese de outros cânceres, como os de cabeça e pescoço. Existem evidências do aumento de incidência dos cânceres de orofaringe associados à infecção pelo HPV. Além disso, parece haver melhor prognóstico desses cânceres associados ao HPV, comparados aos não associados. Por outro lado, existem também alusões na literatura à associação da infecção pelo HPV a outros tipos de cânceres, como os cânceres de esôfago, de bexiga, de pulmão e de mama. Essas informações têm aplicação potencial para eventuais programas de triagem em subgrupos de risco. Atualmente, a vacinação contra o HPV, aprovada para a prevenção do câncer do colo uterino, poderia ter papel potencial na prevenção de outros cânceres associados a essa infecção. Além disso, há interesse no desenvolvimento de tratamentos especificamente dirigidos ao subgrupo de cânceres associados ao HPV. Nesta revisão, foi discutido o possível papel da infecção pelo HPV em cânceres não anogenitais.(AU)

Human papillomavirus (HPV), one of the most common sexually infection transmitted worldwide, has an established role in the pathogenesis of genital and anal malignancies. The HPV has also been implicated in the oncogenesis of other cancers, including head and neck malignancies. There are evidences that the increase of oropharyngeal cancer?s incidence is associated with HPV infection. Besides, these cancers, which are associated to HPV, show improved outcomes compared of those not associated with HPV infection. On the other hand, there are also references regarding the association of HPV infection with other cancers, as the esophagus, bladder, lung and breast cancers. This information has potential implications for the eventual screening of high-risk groups. While HPV vaccination is currently approved for the prevention of cervical cancers, it also has potential in the prevention of all HPV-associated malignancies. Moreover, there is interest in designing treatments specifically for this HPV-positive subgroup. In this review, the role of HPV in non-anogenital cancers was discussed.(AU)

A portrait of single and multiple HPV type infections in Brazilian women of different age strata with squamous or glandular cervical lesions.

BACKGROUND: Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Our objective was to assess the relationships between single- (ST) and multiple-type (MT) HPV infections with patients' age and lesion pathological status. METHODS: 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across histological types and age strata. RESULTS: 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59. CONCLUSIONS: Our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18.

Prevalence, genotype profile and risk factors for multiple human papillomavirus cervical infection in unimmunized female adolescents in Goiânia, Brazil: a community-based study.

BACKGROUND: The epidemiology of infection with multiple human papillomavirus (HPV) types in female adolescents is poorly understood. The purpose of this study was to explore the epidemiology of infection with multiple HPV types in adolescents and its association with demographic, behavioral and biological variables, as well as with cytological abnormalities. METHODS: This community-based study included 432 sexually active females between 15 and 19 years of age. Genotyping for 30 HPV types was performed using a reverse blot strip assay/restriction fragment length polymorphism. Unconditional multivariate logistic regression was performed to identify factors significantly associated with HPV infection. The association between HPV infection and cytological abnormalities was calculated using a prevalence ratio. RESULTS: The most common HPV types detected were 16, 51, 31, 52 and 18. Of the 121 HPV-positive women, 54 (44.6%) were infected with multiple HPV types. Having more than one lifetime sexual partner was associated with infection with any HPV infection, single HPV infection, and infection with multiple HPV types. The presence of cytological abnormalities was associated with infection with multiple HPV types. CONCLUSIONS: Co-infecting HPV genotypes occur in a high proportion of sexually active adolescents. Socio-demographic or sexual behavior factors associated with single HPV infection were similar to those associated with multiple HPV types. The higher risk of cytological abnormalities conferred by infection with multiple HPV types suggests a potential role of co-infection in the natural history of HPV infection.

Association between HPV types and species groups and cervical neoplasia from a high-risk area for cervical cancer, Goiânia, Brazil.

This study was designed to evaluate the effect of single or multiple-human papillomavirus (HPV) infection and phylogenetic groups on the prevalence and severity of cervical intraepithelial neoplasia (CIN) in women undergoing colposcopy after an abnormal cervical smear. Colposcopy was performed in 198 cases and biopsy was performed in 193 patients. All specimens were tested for 27 HPV genotypes using the Roche polymerase chain reaction reverse line blot assay. The overall prevalence of HPV infection in women with an abnormal cervical smear was 86% (171 of 198). The prevalence of HPV 16 in high-grade CIN (2/3) was 52% (40 of 76), being detected in 88.8% of cases (8 of 9) of invasive carcinoma. The prevalence of HPV types 31 and 35 in high-grade CIN was 10.5% (8 of 76) and 6.6% (5 of 76), respectively. Single or multiple-type infection involving HPV 16 were significantly associated with a diagnosis of high-grade neoplasia (≥ CIN 2) [odds ratio (OR) 6.49; 95% confidence interval (CI): 1.88-23.44 and OR: 3.65; 95% CI: 1.13-12.15] even after adjustment for HPV-DNA. A statistically significant association was also found between HPV 16 and the other HPV types belonging to species α 9 and a diagnosis of high-grade neoplasia (OR: 7.62; 95% CI: 1.28-51.58); however, no association was found between HPV 16 and the other HPV types belonging to species α 7. HPV 16 is the most important predictor of high-grade cervical neoplasia. Multiple-type infections are predictors of high-grade cervical neoplasia when type 16 is present.