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BACKGROUND AND OBJECTIVES: The 9-valent human papillomavirus (9vHPV) vaccine Phase III immunogenicity study in 9- to 15-year-old boys and girls was extended to assess immunogenicity and effectiveness through 10 years after the last vaccine dose (NCT00943722). METHODS: Boys (n = 301) and girls (n = 971) who received three 9vHPV vaccine doses in the base study (day 1, months 2 and 6) enrolled in the extension. Serum was collected through month 126 for antibody assessments by competitive Luminex immunoassay and immunoglobulin G-Luminex immunoassay. For effectiveness analysis starting at age 16 years, genital swabs were collected (to assess HPV DNA by polymerase chain reaction) and external genital examinations conducted every 6 months. Primary analyses were conducted in per-protocol populations. RESULTS: Geometric mean antibody titers peaked around month 7, decreased sharply between months 7 and 12, then gradually through month 126. Seropositivity rates remained ≥81% by competitive Luminex immunoassay and ≥95% by immunoglobin G-Luminex immunoassay at month 126 for each 9vHPV vaccine type. After up to 11.0 (median 10.0) years of follow-up postdose 3, there were no cases of HPV6/11/16/18/31/33/45/52/58-related high-grade intraepithelial neoplasia or condyloma in males or females. Incidence rates of HPV6/11/16/18/31/33/45/52/58-related 6-month persistent infection in males and females were low (54.6 and 52.4 per 10000 person-years, respectively) and within ranges expected in vaccinated cohorts, based on previous human papillomavirus vaccine efficacy trials. CONCLUSIONS: The 9vHPV vaccine demonstrated sustained immunogenicity and effectiveness through â¼10 years post 3 doses of 9vHPV vaccination of boys and girls aged 9 to 15 years.
RESUMEN
OBJECTIVES: To describe the expression of vascular endothelial growth factor (VEGF), proto-oncogene macrophage colony-stimulating factor receptor (c-fms) and cyclooxygenase-2 (COX-2) in cervical carcinogenesis and to analyze the correlation of VEGF with c-fms and COX-2 expression. METHODS: In this study, 26 cases of benign cervix, 28 low-grade cervical intraepithelial neoplasia (CIN; CIN 1), 30 high-grade CIN (CIN 2/3) and 28 squamous cervical carcinomas (SCC) were examined by immunohistochemistry (IHC) and analysis was performed separately for epithelium and stroma. RESULTS: Positive epithelial expressions in normal cervix, low-grade CIN, high-grade CIN and SCC were, respectively: VEGF - 11.5%, 39.3%, 53.3% and 75% (P<0.001); c-fms - 0%, 10.7%, 40% and 67.9% (P<0.001); COX-2 - 7.7%, 39.3%, 80% and 100% (P<0.001). Stromal VEGF expression was higher than epithelial expression in all CIN grades and was also associated with the lesion grade, while c-fms and COX-2 stromal expression was weak. VEGF expression was statistically correlated to c-fms and COX-2 expression in high-grade CIN (P=0.020 and P=0.027, respectively) and SCC (P=0.015 and P=0.005, respectively). CONCLUSIONS: On the basis of our findings, these factors may participate in the development and progression of CIN lesions, with possible interaction of c-fms and COX-2 on VEGF expression, and may be potential molecular targets for studies of cervical cancer prevention and treatment.
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Carcinoma de Células Escamosas/metabolismo , Ciclooxigenasa 2/biosíntesis , Receptor de Factor Estimulante de Colonias de Macrófagos/biosíntesis , Displasia del Cuello del Útero/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Ciclooxigenasa 2/genética , Femenino , Humanos , Inmunohistoquímica , Invasividad Neoplásica , Estadificación de Neoplasias , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Proto-Oncogenes Mas , Receptor de Factor Estimulante de Colonias de Macrófagos/genética , Regulación hacia Arriba , Neoplasias del Cuello Uterino/irrigación sanguínea , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Factor A de Crecimiento Endotelial Vascular/genética , Displasia del Cuello del Útero/irrigación sanguínea , Displasia del Cuello del Útero/genética , Displasia del Cuello del Útero/patologíaRESUMEN
OBJECTIVE: To evaluate the colposcopic accuracy according to the International Federation for Cervical Pathology and Colposcopy (IFCPC) 2002 terminology. MATERIALS AND METHODS: A series of 3,040 women derived from a general population were screened by means of Pap smear, unaided visual inspection, and high-risk human papillomavirus testing. All colposcopic examination results with abnormal findings and with biopsy confirmation (n = 468) were recorded, reviewed by 2 blinded colposcopists according to the IFCPC nomenclature, and included in this analysis. RESULTS: The IFCPC terminology was easily reproduced by the 2 observers with excellent interobserver agreement (kappa =.843). Colposcopy had a sensitivity of 86% and a specificity of 30.3% in distinguishing healthy cervix from that with cervical intraepithelial neoplasia (CIN)/carcinoma. In distinguishing healthy cervix/low-grade lesions (CIN 1) from that with high-grade lesions (CIN 2/3)/carcinoma, colposcopy had a sensitivity of 61.1% and a specificity of 94.4%. Colposcopic findings graded as major changes had the highest positive predictive value for detecting high-grade lesion/carcinoma. The colposcopic abnormalities within the transformation zone and large lesions were more closely related to high-grade lesion/carcinoma, whereas a sharp outer border, multiple colposcopic abnormalities, and iodine negativity were not statistically related to severe lesions. CONCLUSIONS: Colposcopy using the new IFCPC classification is a potentially effective screening method; when used for diagnosis, a histological sampling is necessary. The categorization of major changes and minor changes is appropriate. It is important to describe the lesion localization in relation to the transformation zone and the lesion size because these characteristics are related to high-grade lesions.
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Colposcopía , Terminología como Asunto , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Colposcopía/clasificación , Femenino , Humanos , Persona de Mediana Edad , Variaciones Dependientes del Observador , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/clasificación , Displasia del Cuello del Útero/clasificaciónRESUMEN
OBJECTIVE: To evaluate the population of macrophages during the cervical malignant transformation and its influence in CIN outcome. METHODS: Biopsies from 26 normal cervix, 28 low-grade (LSIL), 30 high grade squamous intraepithelial lesions (HSIL) and 28 squamous cell carcinomas (SCC) were stained by H&E to assess inflammation and by immunohistochemistry with anti-CD68 to detect macrophages. The macrophage count was corrected for the epithelial and stromal compartments using appropriate software. Clinical and prospective follow-up data were also available. RESULTS: We identified that macrophage count increased linearly with disease progression (median count per case at x200 magnification: normal, 5.1; LSIL, 5.5; HSIL, 9.9; SCC, 14.5; P<0.001), that inflammation also increased (moderate-intense inflammation present in 25%, 46.1%, 58.4% and 89.3% of normal, LSIL, HSIL and SCC, respectively; P<0.001) and that macrophage count was independently associated with the lesion grade (P<0.001). Moreover, macrophages showed an increasing migration into the epithelium along with the progression of CIN to invasive cancer. Of the 24 LSIL cases with information available, followed-up for 805+/-140 days, 16 regressed, 6 persisted and 2 progressed. Age, high-risk HPV or inflammation were not risk factors for persistent/progressed LSIL in our cohort. However, LSIL that persisted or progressed showed a higher macrophage count (median of 10.8) than lesions that regressed (7; P=0.031). CONCLUSIONS: The study on macrophages offers a potential approach for cervical cancer treatment, since macrophages are closely related to progression of CIN, and can be used as an applicable marker of such a risk.
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Carcinoma de Células Escamosas/patología , Transformación Celular Neoplásica/patología , Macrófagos/patología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Antígenos CD/química , Antígenos de Diferenciación Mielomonocítica/química , Carcinoma de Células Escamosas/inmunología , Transformación Celular Neoplásica/inmunología , Femenino , Humanos , Inmunohistoquímica , Inflamación/inmunología , Inflamación/patología , Macrófagos/inmunología , Factores de Riesgo , Neoplasias del Cuello Uterino/inmunología , Displasia del Cuello del Útero/inmunologíaRESUMEN
OBJECTIVE: To compare the expulsion rates of intrauterine devices (IUDs) inserted in the immediate postpartum after vaginal birth and cesarean section. METHODS: Nineteen patients who had a vaginal birth and 19 patients who had a cesarean section at Hospital de Clínicas de Porto Alegre, Brazil, were selected for copper T 380A IUD insertion. With the aim of detecting clinically unnoticed dislodged devices, ultrasound examinations were performed at 1 month and between 3 and 12 months after delivery. The IUDs were considered completely expelled when found outside the endometrial cavity (e.g., in the cervical canal) or outside the uterus (in the vagina). RESULTS: Expulsion rates were statistically different between the two groups: after a vaginal birth, 50% (ultrasound only) + 27.8% (clinical examination); and post-cesarean section, 0% (p < .001; OR 5.75, 95% CI 2.36-14.01). CONCLUSION: Considering that the contraceptive efficacy of IUDs is associated with their intrauterine location, the high expulsion rates seen when they are inserted immediately after vaginal delivery contraindicate their use in this setting. The use of IUDs immediately after a cesarean section is still a reasonable alternative because its expulsion rate was zero. Ultrasound assessment of IUD positioning performed better than clinical examination, which failed to detect expulsion after postpartum insertion in 75% of the cases (9 from 12 cases).