Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Extension study of the safety and efficacy of CLS-TA for treatment of macular oedema associated with non-infectious uveitis (MAGNOLIA).

PURPOSE: To assess the extended efficacy and safety of suprachoroidal triamcinolone acetonide injectable suspension (CLS-TA) among patients with macular oedema (ME) secondary to non-infectious uveitis (NIU). METHODS: Patients with uveitic ME were treated with suprachoroidal CLS-TA at baseline and week 12 of the Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial (PEACHTREE) study. Time to rescue was evaluated over 24 additional weeks for MAGNOLIA. Safety data, visual acuity and retinal central subfield thickness (CST) reduction were also evaluated. Of the 53 eligible patients (46 CLS-TA and 7 control), 33 patients were enrolled (28 CLS-TA and 5 control). RESULTS: Over the entire 48-week period for PEACHTREE and MAGNOLIA, the median time to rescue therapy was 257 days versus 55.5 days for the CLS-TA and sham-control arms, respectively. Of 28 CLS-TA treated patients who participated in MAGNOLIA, 14 (50%) did not require rescue therapy through approximately 9 months after the second treatment. Among CLS-TA patients not requiring rescue, there was a mean gain of 12.1 letters and mean CST reduction of 174.5 µm at week 48. No serious adverse events related to study treatment were observed. CONCLUSION: Approximately 50% of patients did not require additional treatment for up to 9 months following the last CLS-TA administration.

Association of genetic variants in RAB23 and ANXA11 with uveitis in sarcoidosis.

Purpose: Uveitis occurs in a subset of patients with sarcoidosis. The purpose of this study was to determine whether genetic variants that have been associated previously with overall sarcoidosis are associated with increased risk of developing uveitis. Methods: Seventy-seven subjects were enrolled, including 45 patients diagnosed with sarcoidosis-related uveitis as cases and 32 patients with systemic sarcoidosis without ocular involvement as controls. Thirty-eight single nucleotide polymorphisms (SNPs) previously associated with sarcoidosis, sarcoidosis severity, or other organ-specific sarcoidosis involvement were identified. Allele frequencies in ocular sarcoidosis cases versus controls were compared using the chi-square test, and p values were corrected for multiple hypotheses testing using permutation. All analyses were conducted with PLINK. Results: SNPs rs1040461 and rs61860052, in ras-related protein RAS23 (RAB23) and annexin A11 (ANXA11) genes, respectively, were associated with sarcoidosis-associated uveitis. The T allele of rs1040461 and the A allele of rs61860052 were found to be more prevalent in ocular sarcoidosis cases. These associations remained after correction for the multiple hypotheses tested (p=0.01 and p=0.02). In a subanalysis of Caucasian Americans only, two additional variants within the major histocompatibility complex (MHC) genes on chromosome 6, in HLA-DRB5 and HLA-DRB1, were associated with uveitis as well (p=0.009 and p=0.04). Conclusions: Genetic variants in RAB23 and ANXA11 genes were associated with an increased risk of sarcoidosis-associated uveitis. These loci have previously been associated with overall sarcoidosis risk.

Pre-papillary vitreous opacities associated with Behçet's disease: a case series and review of the literature.

PURPOSE: To present pre-papillary vitreous opacity as an uncommon manifestation of inflammation in Behçet's disease that may be specific to this uveitic entity. METHODS: We retrospectively reviewed the charts of 67 patients with Behçet's disease examined at our clinic between 2005 and 2016. Behçet's disease was diagnosed based on established clinical criteria of inflammation involving the eyes, mucocutaneous junctions, and skin. Patients with Behçet's disease who presented with papillitis and a pre-papillary vitreous opacity were identified. Response to anti-inflammatory treatment on examination and optical coherence tomography imaging were evaluated. PubMed searches were performed for (1) other cases with pre-papillary vitreous opacities in uveitic entities and (2) reports of optic nerve involvement specifically in Behçet's disease. RESULTS: We identified three patients with Behçet's disease who presented with unilateral papillitis and a pre-papillary vitreous opacity. The pre-papillary vitreous opacity had a funnel-shaped appearance on optical coherence tomography. All patients were initially treated with steroids, which led to resolution of the opacity clinically and on imaging. We identified one previous report of such a pre-papillary opacity in a patient with Behçet's disease, and no reports of this finding in other uveitic entities. CONCLUSION: This study expands the number of Behçet's disease cases presenting with a pre-papillary vitreous opacity and demonstrates novel optical coherence imaging of this finding. This finding may be specific to Behçet's disease as it was not identified in other uveitic entities in a review of the existing literature.

Accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as a research tool for identification of patients with uveitis and scleritis.

PURPOSE: To report on the accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for identifying patients with polymyalgia rheumatica (PMR) and concurrent noninfectious inflammatory ocular conditions in a large healthcare organization database. METHODS: Queries for patients with PMR and uveitis or scleritis were executed in two general teaching hospitals' databases. Patients with ocular infections or other rheumatologic conditions were excluded. Patients with PMR and ocular inflammation were identified, and medical records were reviewed to confirm accuracy. RESULTS: The query identified 10,697 patients with the ICD-9-CM code for PMR and 4154 patients with the codes for noninfectious inflammatory ocular conditions. The number of patients with both PMR and noninfectious uveitis or scleritis by ICD-9-CM codes was 66. On detailed review of the charts of these 66 patients, 31 (47%) had a clinical diagnosis of PMR, 43 (65%) had noninfectious uveitis or scleritis, and only 20 (30%) had PMR with concurrent noninfectious uveitis or scleritis confirmed based on clinical notes. CONCLUSIONS: While the use of ICD-9-CM codes has been validated for medical research of common diseases, our results suggest that ICD-9-CM codes may be of limited value for epidemiological investigations of diseases which can be more difficult to diagnose. The ICD-9-CM codes for rarer diseases (PMR, uveitis and scleritis) did not reflect the true clinical problem in a large proportion of our patients. This is particularly true when coding is performed by physicians outside the area of specialty of the diagnosis.

Side-effects of anti-inflammatory therapy in uveitis.

Uveitis is a group of inflammatory ocular conditions that cause significant visual morbidity around the world. Many of the cases of blindness secondary to uveitis can be avoided with adequate and aggressive management of the intraocular inflammation. Steroids have been utilized in the treatment of noninfectious uveitis for more than 60 years, but their chronic use is associated with severe ocular and systemic side-effects. Ophthalmologists are often not familiar with the systemic steroid-sparing agents available for the management of ocular inflammation and depend primarily on the use of corticosteroids. In this article, we review the most common agents utilized in the treatment of uveitis and their side-effect profiles.

Disruption and destabilization of meibomian lipid films caused by increasing amounts of ceramides and cholesterol.

PURPOSE: We evaluated quantitatively direct effects of ceramide (Cer) and free cholesterol (FC) on meibomian lipid films (MLF) using a Langmuir trough (LT) and a Brewster angle microscope (BAM). METHODS: Meibum was obtained from healthy volunteers. A series of mixtures of meibum with Cer or FC (mixed MLF) taken in different ratios were tested. Standard rheologic parameters, such as elasticity and hysteresis of MLF, were computed. BAM was used to study the morphology of MLF. RESULTS: Pure MLF were capable of withstanding multiple compression/expansion cycles with little hysteresis observed (1.9 J/G meibum). The films made of either pure CER or pure FC were clearly collapsible, and had much higher rigidity and hysteresis than pure meibum. Adding progressively higher amounts of CER or FC to meibum had a strong impact on the rigidity, stability, and morphology of the mixed MLF: their hysteresis increased many fold compared to pure meibum. A concomitant increase in the rigidity and collapsibility of the mixed MLF was observed. CONCLUSIONS: Cer and FC changed the surface properties of mixed MLF in a way that implied their destabilization and/or disruption. One of the mechanisms that might lead to these effects is strong aggregation of meibum lipids with FC or Cer that leads to the formation of smaller particles of meibum surrounded by a thinner layer of FC or Cer. As Cer and FC can be elevated in meibum and the tear film because of certain pathologic processes, or can be of exogenous nature, our results can explain (partially) a less stable tear film in those subjects.

Pilot, prospective, randomized, double-masked, placebo-controlled clinical trial of an omega-3 supplement for dry eye.

PURPOSE: To investigate the potential effect of dietary supplementation with omega-3 fatty acid on lipid composition of meibum, aqueous tear evaporation, and tear volume in patients with dry eye. METHODS: In a pilot, prospective, randomized, double-masked study, patients with dry eye received a daily dose of fish oil, containing 450 mg of eicosapentaenoic acid, 300 mg of docosahexaenoic acid, and 1000 mg of flaxseed oil (TheraTears Nutrition; Advanced Vision Research, Woburn, MA) for 90 days. There were 2 patient visits: baseline and final. At these visits, patients completed the ocular surface disease index to score subjective symptoms, and slit-lamp examinations, breakup time, corneal staining, Schirmer type I, fluorophotometry, evaporometry, and collection of meibomian gland secretion samples for lipid composition analysis were performed. RESULTS: A total of 36 patients with dry eye completed the study. At the end of the study, 70% of the patients became asymptomatic, whereas for the placebo group, 37% [corrected] of the symptomatic patients became asymptomatic. Schirmer testing and fluorophotometry suggested that the omega-3 supplement increased tear secretion. The lipid composition of the samples collected from the omega-3 group was found to be very similar to that from the placebo group. No trends between groups were seen for other objective parameters. CONCLUSIONS: Dietary supplementation with omega-3 fatty acids in dry eye showed no significant effect in meibum lipid composition or aqueous tear evaporation rate. On the other hand, the average tear production and tear volume was increased in the omega-3 group as indicated by both Schirmer testing and fluorophotometry.

Impact on ocular surface evaporation of an artificial tear solution containing hydroxypropyl guar.

OBJECTIVE: To determine whether any acute effects on evaporative parameters are produced when using a solution containing Hydroxypropyl (HP) (Systane) versus normal saline solution in the eyes of patients with Keratoconjunctivis Sicca at 30 and 60 minutes postinstillation. METHODS: Randomized double-blinded placebo-control 2-period cross-over clinical trial. Twelve patients with a clinical diagnosis of Keratoconjunctivis Sicca were enrolled in this study. Aqueous tear evaporation was measured at baseline, i.e., before the application of drops on the eye, and at 30 and 60 minutes after instillation of one 40 microL drop of either the HP-Guar containing drop or normal saline on two separate days. Statistical analysis included descriptive data analysis and paired t test. RESULTS: Hydroxypropyl-Guar resulted in a decrease in aqueous tear evaporation at 30 minutes postinstillation under 25% to 35% relative humidity (RH) (13.2% reduction, P=0.044) and 35% to 45% RH (10% reduction, P=0.028) conditions. The effect of HP-Guar at 60 minutes postinstillation also decreased aqueous tear evaporation but to a lesser degree. Normal saline solution produced no statistically significant increases and decreases of evaporation. CONCLUSIONS: Aqueous tear evaporation contributes significantly to aqueous tear loss and is humidity dependent. An HP-guar containing solution decreased aqueous tear evaporation 30 and 60 minutes after application. The use of topical medication with known antievaporative effect may be beneficial in dry eye therapy. This effect may also be achieved in normal eyes or sub-clinical dry eyes when in low RH environments.

Lipids of human meibum: mass-spectrometric analysis and structural elucidation.

The purpose of this study was to structurally characterize the major lipid species present in human meibomian gland secretions (MGS) of individual subjects by means of ion trap atmospheric pressure ionization mass spectrometry analysis (API MS(n)). The samples of MGS and authentic lipid standards were analyzed in direct infusion and high-pressure liquid chromatography (HPLC) experiments with API MS(n) detection of the analytes (HPLC API MS(n)). The major precursor ions were isolated and subjected to further sequential fragmentation in MS(n) experiments, and their fragmentation patterns were compared with those of authentic lipid standards. Multiple precursor ions were observed in the positive-ion mode. Among those, previously identified cholesterol (Chl; m/z 369; [M - H(2)O + H](+)) and oleic acid (OA; m/z 283; [M + H](+)) were found. The other major compounds of the general molecular formula C(n)H(2n-2)O(2) were consistent with wax esters (WEs), with OA as fatty acyl component. Accompanying them were two homologous series of compounds that fit the molecular formulas C(n)H(2n-4)O(2) and C(n)H(2n)O(2). Subset 2 was found to be a homolog series of linoleic acid-based WEs, whereas subset 3 was, apparently, a mixture of stearic acid-based WEs. HPLC API MS(n) analysis revealed the presence of large quantities of cholesteryl esters (Chl-Es) in all of the tested samples. Less than 0.1% (w/w) of oleamide was detected in human MGS. In the negative-ion mode, three major compounds with m/z values of 729, 757, and 785 that were apparently related to anionogenic lipids of the diacylglyceryl family were found in all of the samples. Common phospholipids and ceramides (Cers) were not present among the major MGS lipids. Phosphocholine-based lipids were found in MGS in quantities less than 0.01% (w/w), if at all. This ratio is two orders of magnitude lower than reported previously. These observations suggest that MGS are a major source of nonpolar lipids of the WE and Chl-E families for the tear film lipid layer, but not of its previously reported (phospho)lipid, Cer, and fatty acid amide components.

Increased evaporative rates in laboratory testing conditions simulating airplane cabin relative humidity: an important factor for dry eye syndrome.

PURPOSE: To quantitatively explore the relationship between low relative humidity conditions, as experienced in airplane cabins during flight, and increases in aqueous tear evaporation as a potential explanation for increased dry eye symptoms noted by people when in low humidity environmental conditions. METHODS: Prospective experimental laboratory study. Evaporative rates under two different ranges of increasing relative humidity, from 20% to 25% (similar to the relative humidity in airplane cabins or arid regions) and from 40% to 45% (similar to the relative humidity in nonarid regions), were obtained from 18 patients with dry eye and 11 healthy subjects. RESULTS: Statistically significant differences were found within all groups: patients with dry eye (divided into keratoconjunctivitis sicca [P=0.001] and meibomian gland dysfunction [P=0.007]) and healthy subjects (P

Pattern of vital staining and its correlation with aqueous tear deficiency and meibomian gland dropout.

PURPOSE: To assess the relationship between the degree and anatomic location of ocular surface vital staining and the degree of aqueous tear deficiency in patients with dry eye, as measured by the Schirmer test, and the presence of meibomian gland dropout. METHODS: Twenty-two patients with dry eye (nine men and 13 women; mean age, 60 years) were prospectively enrolled in the study. Eleven subjects with no ocular disease were considered control subjects. Lissamine green vital staining, Schirmer test, and meibomian gland dropout were evaluated. RESULTS: Patients were stratified based on their vital staining pattern (presence or absence of corneal staining). A progressive decrease in the Schirmer test result was found when the vital staining score increased (r = -0.655; P<0.0001). Patients with dry eye showed an increase in meibomian gland dropout when compared to control subjects (P

Liquid chromatography-mass spectrometric analysis of lipids present in human meibomian gland secretions.

The purpose of the study was to qualitatively characterize the major lipid species present in human meibomian gland secretions (MGS) by means of high-performance liquid chromatography with atmospheric pressure ionization mass spectrometric detection of the analytes (NP HPLC-MS). Two different NP HPLC-MS methods have been developed to analyze lipid species that were expected to be present in MGS. The first method was optimized for the analysis of relatively nonpolar lipids [wax esters (WE), di- and triacyl glycerols (DAG and TAG), cholesterol (Chl) and its esters (Chl-E), and ceramides (Cer)], while the second method was designed to separate and detect phospholipids. The major lipid species in MGS were found to be WE, Chl-E, and TAG. A minor amount of free Chl (less then 0.5% of the Chl-E fraction) was detected in MGS. No appreciable amounts of DAG and Cer were found in MGS. The second NP HPLC-MS method, capable of analyzing model mixtures of authentic phospholipids (e.g. phosphatidylglycerol, phosphatidylethanolamine, phosphatidic acid, phosphatidylinositol, phosphatidylserine, phosphatidylcholine, and sphingomyelin) in submicrogram/mL concentrations, showed little or no presence of these species in the MGS samples. These observations suggest that MGS are a major source of the nonpolar lipids of the WE and Chl-E families for the tear film lipid layer (TFLL), but not of the previously reported phospholipid components of the TFLL.

Correlations in a change in aqueous tear evaporation with a change in relative humidity and the impact.

PURPOSE: To establish scientific relationship between relative humidity (RH) and aqueous tear evaporation to elucidate possible significance of this relationship in normals and aqueous tear deficiency patients. DESIGN: Prospective experimental laboratory study. METHODS: Ocular surface evaporation was determined using evaporometry and calculated for two ranges of RH, 25% to 35%, and 35% to 45% in a randomized clinical patient population. RESULTS: Average evaporative rate in the higher humidity range was between 0.029 +/- 0.009 through 0.043 +/- 0.016 microl/cm2/min. At lower humidity, range was between 0.044 +/- 0.013 through 0.058 +/- 0.018 microl/cm2/min. Differences in the corresponding evaporative rates were statistically significant (between P < .003 through P < .043) for each analysis. CONCLUSIONS: A decrease of 10% RH resulted in an average difference of between 28.33% to 59.42% increase in evaporation. The increase in evaporation at lower humidity has significant clinical implications for patients with aqueous deficient dry eyes, and possibly those undergoing laser-assisted in situ keratomileusis (LASIK).

Impact of evaporation on aqueous tear loss.

PURPOSE: To determine the impact of evaporation on preocular aqueous tear (AT) loss in normal subjects (controls) and patients with keratoconjunctivitis sicca (KCS). METHODS: Eighteen patients (32 eyes) with KCS with or without associated meibomian gland dysfunction (MGD) and 11 sex-matched controls had AT evaporation determined between relative humidity (RH) of 20% and 45% using an evaporometer. AT volume, flow, and turnover were determined with a fluorophotometer. RESULTS: Evaporative rates increased significantly when the RH was changed from 40%-45% to 20%-25% (P < .001). This change was similar in all groups and on average accounted for a 99.43% increase. There were no statistically significant differences in evaporative rate between controls, the KCS alone group, and the KCS/MGD group. Dry eye patients exhibited a decreased tear turnover when compared to controls. Evaporative contribution to tear loss at 40%-45% RH was 23.47% for controls, 30.99% for "classic" KCS patients, and 25.44% for KCS/MGD patients. At 20%-25% RH, the evaporative contribution was 41.66% for controls, 57.67% for classic KCS patients, and 50.28% for KCS/MGD patients. CONCLUSIONS: RH significantly impacts evaporation regardless of the presence of dry eye disease and probably accounts for the increased dry eye symptoms in people (controls and dry eye patients) in conditions of low RH (eg, deserts, airplane cabins, cold dry seasons). Contribution of evaporation to tear loss tends to be higher than previously described. The percent contribution is dependent on environmental conditions such as RH. There was a trend toward increased contribution to AT loss in dry eye patients vs controls, but statistical significance was not reached.

Factores de riesgo en cáncer de cuello uterino / Risk factors in uterine cervical cancer

Objetivo: Identificar los factores de riesgo del cáncer de cuello uterino. Diseño: Se realizó un estudio retrospectivo descriptivo de enero de 1995 a marzo de 1996, de pacientes que consultaron al Departamento de Ginecología-Obstetricia del Hospital Regional Docente "Las Mercedes" de Chiclayo. Se revisó las fichas de Registro de Cáncer Ginecológico, incluyéndose 110 pacientes con diagnóstico de cáncer de cuello uterino. La patología fue confirmada con estudio histológico de biopsia de cuello uterino en el 95 por ciento de los casos. Resultados: El promedio de edad fue de 47 años. El 38,2 por ciento fue conviviente. El 41 por ciento procedió de Chiclayo y distritos. 68 mujeres nunca tuvieron Papanicolaou previo. El promedio de edad de inicio de relaciones sexuales fue de 18,4 años. 21 por ciento tuvo más de un compañero sexual. El promedio de hijos por paciente fue de 6,4. 77,3 por ciento fueron cáncer avanzado (II, III y IV). El inicio de las relaciones sexuales a temprana edad y el número elevado de hijos son los factores de riesgo encontrados. El número de compañeros sexuales en ambos sexos debe ser evaluado. Conclusiones: Esta neoplasia es un problema de salud pública: el 77,3 por ciento son estadíos avanzados, sólo el 41 por ciento procede de Chiclayo y 61,8 por ciento nunca tuvo Papanicolaou previo. Este estudio servirá de base para proyectos posteriores de otro diseño. Palabras clave: Factores de riesgo, cáncer de cuello uterino, Papanicolaou.