Controversia en el tratamiento de la lesión intraepitelial escamosa de alto grado (NIC II) / Controversy in the treatment of high-grade squamous intraepithelial lesion (CIN II)

Contexto: el cono LLETZ actualmente es el tratamiento de las NIC de alto grado. La resistencia al procedimiento es argumentada por los efectos del sobretratamiento (estenosis e insuficiencia cervical), sobre todo cuando se utilizan métodos ablativos destructivos en lugar de la resección quirúrgica ambulatoria (LLETZ). Objetivo: analizar el diagnóstico y tratamiento del NIC II mediante cono y legrado en pacientes que acuden al servicio de Patología del tracto genital inferior del Hospital Oncológico SOLCA-Quito Ecuador. Sujetos y métodos: en este estudio epidemiológico descriptivo observacional de corte transversal se analizaron expediente clínicos de 820 pacientes con diagnóstico histopatológico por biopsia de NIC II; mujeres entre 17 a 82 años que acudieron al servicio de patología del tracto genital inferior sujetas a control, en estas pacientes se realizó 530 legrados. El estudio fue realizado en el Hospital Oncológico SOLCA de Quito Ecuador, de los años 2004 a 2013. Resultados: la histopatología de los conos libres de neoplasia representa el 98,66% (n=809); existen 11 casos de neoplasias residuales (1,34%). El 53,7% de casos presenta una lesión igual o mayor que en biopsia, lo que justifica el cono. Conclusión: el procedimiento de cono LLETZ tiene gran utilidad diagnóstica, terapéutica y pronóstica en mujeres que presentan NIC II y otras patologías similares. (AU)

Background: the LLETZ cone is currently the treatment of high grade NICs. The resistance to the procedure is argued by the effects of overtreatment (stenosis and cervical insufficiency), especially when destructive ablative methods are used instead of ambulatory surgical resection (LLETZ). Objective: to analyze the diagnosis and treatment of CIN II by means of cone and curettage in patients attending the pathology department of the lower genital tract of the SOLCA-Quito Ecuador Oncology Hospital. Subjects and methods: in this cross-sectional descriptive epidemiological observational study, we analyzed clinical records of 820 patients with histopathological diagnosis by CIN II biopsy; women between 17 and 82 years old who visited the pathology service of the lower genital tract subject to control, in these patients 530 catheters were performed. The study was conducted at the SOLCA Oncology Hospital of Quito, Ecuador, from 2004 to 2013. Results: the histopathology of neoplasm-free cones represents 98.66% (n = 809); there are 11 cases of residual neoplasms (1.34%). 53.7% of cases present a lesion equal to or greater than in biopsy, which justifies the cone.(AU)

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

BACKGROUND: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

Role of Human Papillomavirus in Penile Carcinomas Worldwide.

BACKGROUND: Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. OBJECTIVE: To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. DESIGN, SETTING, AND PARTICIPANTS: After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: HPV DNA prevalence and type distributions were estimated. RESULTS AND LIMITATIONS: HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. CONCLUSIONS: About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions. PATIENT SUMMARY: About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions.

Prevalence of human papillomavirus types in cervical cancerous and precancerous lesions of Ecuadorian women.

Human Papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of uterine cancer. In Ecuador there is limited information about HPV types (and variants) in cancerous lesions; however, identifying the type-specific HPV prevalence in cervical lesions of women living in Ecuador is important to better predict the impact of HPV prophylactic vaccination in this country. We studied the prevalence of HPV types in cervical cancerous or precancerous lesions from 164 Ecuadorian women and found that 86.0% were HPV positive. The most common types were HPV16 (41.8%) and HPV58 (30.5%). Interestingly, HPV18 was detected only in 2.8% of the HPV-positive samples. Fifteen DNA sequences (genes E6 and L1) from 16 samples positive for HPV16 belonged to the European lineage, considered one of the least carcinogenic lineages, and 1 (6.25%) to the Asian-American lineage. Similar analysis in 12 HPV58 positive samples showed that 10 (83.3%) sequences grouped in sublineage A2, which belongs to the oldest HPV58 lineage, 1 belonged to A3 and 1 to lineage C. This study suggests that the currently used HPV vaccines (bivalent and tetravalent) may have lower effectiveness in Ecuador than in other geographic locations where HPV18 is more prevalent.

Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide.

Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16(INK4a) expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1-91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16(INK4a) overexpression was found in 95% of HPV DNA-positive anal cancers. In view of the results of HPV DNA and high proportion of p16(INK4a) overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.

Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva.

BACKGROUND: Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. METHODS: Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). RESULTS: Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). CONCLUSION: Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.

Quiste epidérmico de inclusión en vulva, presentación de un caso / Epidermal inclusion cyst in vulva, presentation of a case

Nosotros presentamos un quiste epidérmico de inclusión diagnóstico clínico, confirmado por histopatología y resuelto quirúrgicamente, paciente de 50 años de edad, con masa inguinal izquierda de doce centímetros de diámetro, se realizo resección y se confirmó por histopatología de lesión de vulva que reportó quiste de inclusión epidérmico de vulva. Se describe la fisiopatología, la morbilidad y mortalidad, evolución clínica, etiología, exámenes complementarios y el tratamiento de estas lesiones.

Tumor neuroendocrinó de vulva: presentación de caso clínico / Neuroendocrine tumor vulva: clinical case presentation

La tasa estandarizada del tumor de vulva más elevada esta en Australia 4,9 por cien mil habitantes, la tasa cruda nacional de Ecuador (2005) es de 0.8 y la tasa estandarizada es 0,8 por cien mil habitantes; el carcinoma neuroendocrino es una entidad rara menor al 0,5% (0,3% FIGO), con pocos casos reportados, el 70% se localizan en los labios mayores o menores. Este tumor se presenta como uno o varios nódulos intradémicos con eritema en la piel circundante, con afectación ganglionar, linfovascular y diseminación hematógena, recurrencia tumoral posterior y sobrevida menor de 35% a 5 años, aunque en tumores con resección total sin compromiso linfático la sobrevida es mayor, o se conoce completamente el comportamiento biológico e historia natural de estos tumores. El tumor de células de Merkel clínicamente es muy agresivo con metástasis en ganglios regionales generalmente luego de un año del diagnóstico. Histológicamente la lesión se encuentra localizada en la derrnis y tejido celular subcutáneo usualmente no presenta conexión con la epidermis. Es necesario el análisis por inmunohistoquimica para definir claramente el diagnóstico.

Diagnóstico de lesiones intracervicales escamosas / Diagnosis of escamosas intracervical injuries

Las lesiones intraepiteliales constituyen los cambios iniciales que se producen a nivel intraepitelial cervical y que pueden evolucionar a un carcinoma. Definitivamente, es en esta etapa donde debe hacerse el mayor énfasis para su detección y manejo, para lo cual la colposcopía constituye la forma correcta de evaluarlas. Con el presente trabajo se revisan los casos de lesiones intraepiteliales que se presentaron durante un año, manejados por el servicio de patología cervical los cuales indican que el 56 por ciento de lesiones se presentan en mujeres > de 35 añso, el 78 por ciento presentan LIE de alto grado, el 82 por ciento presenta una correlación positiva de biopsias e histopatología.

Legrado endocervical en mujeres menopáusicas con colposcopia insatisfactoria

El presente es un estudio prospectivo realizado en 32 mujeres que asistieron a consulta de especialidad en el Instituto del CANCER (SOLCA) de la ciudad de Quito durante Mayo de 1991 a Mayo de 1992 y presentaron colposcopia insatisfactoria. Se considera colposcopia insatisfactoria cuando no se observa la unión escamo-columnar en un cervix atrófico sobretodo en mujeres menopáusicas o que han sido sometidas a tratamientos destructivos como electrocauterización de exocervix. Se observó que el 46.87 por ciento de estos pacientes Ca. invasor; el 25 por ciento presentaron NIC III; el 9.37 por ciento presentaron NIC II y el 18,75 por ciento presentaron Cervicitis Crónica. Posteriormente estas pacientes se sometieron a tratamientos realizándose en el 18,75 por ciento histerectomia radical e incluso un 18.75 por ciento radioterapia. Podemos concluir que este método es de gran utilidad para completar el diagnóstico de la patología cervical uterina y para la estrategia del tratamiento en pacientes post menopáusicas.