Correlação entre a infecção genital pelo vírus do papiloma humano, a resposta imune e os achados colpocitológicos em mulheres grávidas e não grávidas

The genital HPV infection is very common between men and women worldwide, affecting particularly young women, constituting a serious public health problem in less developed regions, favored by the poor living conditions of population. The cytology and colposcopy have notorious importance in the diagnosis of precursor lesions of cervical cancer and therefore its prevention. However, even with such diagnostic tools, the number of women who develop cervical cancer is still high. This study aims to assess the prevalence of genital tract infection by HPV in pregnant and nonpregnant women, evaluating the profile of the immune response presented by the women of these two groups in order to establish correlations among profile of immune response, presence of virus and occurrence of lesions of the uterine cervix. We analyzed specimens obtained from the cervix of 221 patients, 91 pregnant and 130 non-pregnant, aged 14-72 years. The women were subjected to colposcopic and cytologic evaluation detect possible changes in the cervix and then samples were collected in order to perform HPV detection by PCR and real-time PCR for detection of mRNA of pro-inflammatory and anti-inflammatory cytokines. In the present study, the overall prevalence of HPV genital infection was 28.1%; of which 31.9% were pregnant patients and 25.4% in non-pregnant women. Young women under 30 years and those with low educational level education showed a higher risk of HPV infection. Colposcopy showed better correlation with detection of HPV DNA by PCR, when compared to cytology. Generally, HPV infected patients, pregnant or not, exhibited reduced mRNA expression of both pro-inflammatory (IFN-γ, TNF-α) and anti-inflammatory (IL -10) cytokines, when compared to patients not infected by HPV. Nonpregnant patients infected presented increase mRNA expression of IL-17 in patients without injury, whereas those with lesion showed higher mRNA expression of TGF-β. Pregnant women without injury infected exhibited increased mRNA expression of TGF-β. There was no difference in HPV prevalence between pregnant and nonpregnant women. There was a reduction of pro-inflammatory cytokines, except IL-17, in all women infected by HPV. Moreover, we observed an increase of TGF-β in HPV-infected women who are pregnant or not. The results suggest that, in women in this study, HPV infection promoted changes in the profile of cytokines necessary for activation of effective immune response, possibly favoring viral persistence

Cigarette smoking and high-risk HPV DNA as predisposing factors for high-grade cervical intraepithelial neoplasia (CIN) in young Brazilian women

Background. This cross-sectional study was designed to evaluate the role of cigarette smoking and high-risk HPV types as risk factors of CIN 2 and 3 in young, sexually active Brazilian women. Materials and method. A series of 100 consecutive women with abnormal Pap smears were recruited, subjected to colposcopy, punch biopsy, and questionnaire for their social, sexual and reproductive factors. Of these, 77 women between 20 and 35 years of age (median 26.5 years) with biopsy-confirmed CIN 1 or CIN 2 and 3, were enrolled in this study. Representative samples from the exocervix and endocervix were obtained for HPV testing with the Hybrid Capture HPV-DNA assay, including the probes for the oncogenic HPV types (16, 18, 31, 33, 35, 45, 51, 52 and 56). Results. The overall rate of CIN 2 and 3 was 23/77 (29.8%). The women with CIN 1, 2 and 3 did not differ from each other with regard to their age, race, schooling, marital status, life-time number of sexual partners, age at first intercourse, use of oral contraceptives, or parity. However, current cigarette smoking was strongly associated with CIN 2 and 3 (p < 0,001), and among smokers, the risk of high-grade CIN increased in parallel with the time of exposure (years of smoking) p = 0.07), HPV-DNA of the oncogenic types was detected in 43 (56%) women, the risk of being HPV DNA-positive was significantly higher in CIN 2 and 3 as compared with CIN 1 (p = 0.037). Importantly, the prevalence of high-risk HPV types was significantly higher in cigarette smokers than in non-smokers (p = 0.046). Conclusions. The results indicate that the severity of CIN lesions was clearly related to two fundamental risk factors: 1) high-risk HPV types, and 2) current cigarette smoking. These two risk factors were closely interrelated in that the high-risk HPV types were significantly more frequent in current smokers than in non-smokers, suggesting the possibility of a synergistic action between these two risk factors in cervical carcinogenesis.

Prevalência de papiloma vírus (HPV) perianal assintomático em pacientes portadores de HPV genital tratados no Hospital das Clínicas da Faculdade de Medicina de Botucatu

Introduction: Human Papillomavirus (HPV) infection is one of the Sexually Transmitted Diseases (STD) of greatest incidence and prevalence worldwide, and it is presently considered to be a pre-neoplastic lesion. Human Papillomavirus infection has totaled 23.4% of the sexually transmitted diseases reported to the Department of Health, and it is currently the most common in our country. Many patients are asymptomatic carriers. Methods: Twenty patients who had been previously treated for HPV due to genital lesions were referred for the conduction of anuscopy and colposcopy of the perianal region. Results: Males (80%) prevailed over females (20%). Of the total number of patients, only 2 showed lesions as examined by anuscopy (10%). However, 3 other patients showed lesions by means of colposcopy, thus increasing to 5 (25%) the total number of asymptomatic patients who presented perianal lesions. Of the total number of patients with lesions, 4 were males and 1 was a female. Conclusion: The presence of perianal lesions was observed in 10% of the patients with genital lesions by means of simple anal inspection. This figure increased to 25% when anal colposcopy was associated, thus showing the importance of conducting such examination on all patients with increased risk factors for HPV infection in the anal region.

Estudo citocolposcópico anorretal em pacientes com lesões cervicais intraepiteliais de alto grau

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

A eletrocoagulação na terapêutica das lesões intra-epiteliais escamosas de alto grau do colo uterino

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Neoplasia intra-epitelial cervical em mulheres soro-positivas para o vírus da imunodeficiência humana

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Perfil de citocinas no soro e na secreção cervical de mulheres com lesão intraepitelial de baixo grau, lesão intraepitelial de alto grau e carcinoma epidermóide invasor

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Atipias de significado indeterminado em células escamosas cervicais e diagnósticos histológicos na Secretaria de Estado de Saúde do Distrito Federal

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Estudo da frequência das neoplasias intra-epiteliais cervicais em mulheres portadoras do vírus da imunodeficiência humana

Dentre as manifestações ginecológicas mais importantes nas mulheres soropositivas para o HIV, estão o câncer do colo uterino e as neoplasias intra-epiteliais cervicais que lhe são as lesões precurssoras. Neste estudo foram analisadas 36 mulheres soropositivas para o vírus da imunodeficiência humana e 54 soro negativas, com a finalidade de analisar a freqüência de lesões precursoras do câncer uterino cervical. Todas as pacientes foram submetidas ao exame clínico ginecológico, colheita de colpocitologia cérvico-vaginal, colposcopia e à biópsia genital quando o exame colposcópico revelava achados anormais. Nas pacientes soropositivas foram quantificados os linfócitos com receptores CD4 e verificado a aderência ao esquema antiretroviral. Os resultados demonstraram que a freqüência das neoplasias intra-epiteliais cervicais foi semelhante nos dois grupos estudados. Observamos ainda que a maioria das pacientes soropositivas apresentavam contagem de CD4 acima de 200 células / mm3, ou seja eram consideradas imunocompetentes. E que trinta e três pacientes das trinta e seis estudadas eram aderentes ao esquema antiretroviral. Concluímos que as mulheres HIV soropositivas consideradas imunocompetentes e em uso de antiretrovirais apresentaram freqüência de neoplasias intraepiteliais cervico-uterinas semelhantes às mulheres soro negativas incluídas neste estudo. Observamos, ainda, que o HPV é importante cofator no desenvolvimento das neoplasias intra-epiteliais cervicais.

Association between concurrent genital bleeding and cervical cancer: a cross-sectional study

Genital bleeding may be a common symptom among women with cervical cancer. Cross-sectional study evaluating whether the prevalence of cervical smear results is different in women with and without clinical information about concurrent genital bleeding. The sample consisted of 2 324 836 smears; of these, 0.4% had clinical information on genital bleeding. When stratified by age group, women with genital bleeding had a higher chance of a cytological result of a high-grade squamous intraepithelial lesion [30-49 years odds ratio (OR) 2.38; 95% confidence interval (CI) 1.60-3.53 and ≥50 years OR 6.30; 95%CI 3.72-10.67), of squamous cell carcinoma (SCC) (30-49 years OR 24.70; 95%CI 11.96-51.03 and ≥50 years OR 48.91; 95%CI 31.28-76.47) and of atypical glandular cells (30-49 years OR 5.72; 95%CI 3.30-9.93 and ≥50 years OR 11.56; 95%CI 5.96-22.45); there was also a higher chance of adenocarcinoma for women ≥50 years (OR 53.13; 95%CI 28.08-100.51). The sensitivity of genital bleeding for women aged 18-29 years was 0.4% for high-grade squamous intraepithelial lesion (HSIL); for women 30-49 years old the rate was 0.9% for HSIL, 8.6% for SCC and 2.1% for atypical glandular cells of undetermined significance (AGUS), while for women aged from 50 years or more the rates were 2.0% for HSIL, 13.7% for SCC, 3.6% for AGUS and 14.7% for adenocarcinoma. Women ≥30 years old with genital bleeding should be referred for colposcopy to rule out the possibility of cervical cancer.

Valutazione dell’impiego dei test per la genotipizzazione di HPV e l’espressione degli oncogeni virali nel follow-up di donne conizzate per lesioni cervicali di alto grado nello screening del cervico-carcinoma della Regione Emilia-Romagna

Obiettivi: Valutare la prevalenza dei diversi genotipi di HPV in pazienti con diagnosi di CIN2/3 nella Regione Emilia-Romagna, la persistenza genotipo-specifica di HPV e l’espressione degli oncogeni virali E6/E7 nel follow-up post-trattamento come fattori di rischio di recidiva/persistenza o progressione di malattia; verificare l’applicabilità di nuovi test diagnostici biomolecolari nello screening del cervicocarcinoma. Metodi: Sono state incluse pazienti con citologia di screening anormale, sottoposte a trattamento escissionale (T0) per diagnosi di CIN2/3 su biopsia mirata. Al T0 e durante il follow-up a 6, 12, 18 e 24 mesi, oltre al Pap test e alla colposcopia, sono state effettuate la ricerca e la genotipizzazione dell'HPV DNA di 28 genotipi. In caso di positività al DNA dei 5 genotipi 16, 18, 31, 33 e/o 45, si è proceduto alla ricerca dell'HPV mRNA di E6/E7. Risultati preliminari: Il 95.8% delle 168 pazienti selezionate è risultato HPV DNA positivo al T0. Nel 60.9% dei casi le infezioni erano singole (prevalentemente da HPV 16 e 31), nel 39.1% erano multiple. L'HPV 16 è stato il genotipo maggiormente rilevato (57%). Il 94.3% (117/124) delle pazienti positive per i 5 genotipi di HPV DNA sono risultate mRNA positive. Abbiamo avuto un drop-out di 38/168 pazienti. A 18 mesi (95% delle pazienti) la persistenza dell'HPV DNA di qualsiasi genotipo era del 46%, quella dell'HPV DNA dei 5 genotipi era del 39%, con espressione di mRNA nel 21%. Abbiamo avuto recidiva di malattia (CIN2+) nel 10.8% (14/130) a 18 mesi. Il pap test era negativo in 4/14 casi, l'HPV DNA test era positivo in tutti i casi, l'mRNA test in 11/12 casi. Conclusioni: L'HR-HPV DNA test è più sensibile della citologia, l'mRNA test è più specifico nell'individuare una recidiva. I dati definitivi saranno disponibili al termine del follow-up programmato.

Outcome of treated anogenital intraepithelial neoplasia among human immunodeficiency virus-infected women

OBJECTIVE: To determine characteristics and clinical course of high-grade anogenital intraepithelial neoplasia (AIN) in human immunodeficiency virus (HIV)-infected women. STUDY DESIGN: HIV-positive women with biopsy-proven high-grade (II and III) vulvar (VIN), vaginal (VAIN) or perianal intraepithelial neoplasia (PAIN) were identified in the electronic databases of 2 colposcopy clinics. RESULTS: A total of 31 patients were identified from 1992 to 2007, of which 30 had a mean follow-up of 47.7 months (SD = 46.0; range, 2.6-166.2). Of the patients, 77.4% had VIN, 12.9% VAIN and 9.7% PAIN at first diagnosis. Age at diagnosis of IN was 36.2 years (SD +/- 5.2; range, 23.5-47.0). Ninety percent of patients received antiretroviral therapy at first diagnosis of IN; 65% (13 of 20) of patients with a follow-up of > 2 years required a second treatment, and 2 developed invasive vulvar cancer (10%). CONCLUSION: AIN among HIV-positive women shows a high relapse rate despite treatment modality used and a substantial invasive potential.

Correction of erosion after suburethral sling insertion for stress incontinence: results and related sexual function

BACKGROUND: Suburethral slings are commonly used for the surgical treatment of female stress incontinence; occasionally they can cause erosion and dyspareunia. OBJECTIVES: The primary aim of this study is to determine the outcome after reclosure of the vaginal epithelium for suburethral sling erosion. Sexual function was assessed before and after intervention using the Female Sexual Function Index (FSFI) questionnaire. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective case-controlled study in which, between December 2005 and December 2007, we included patients who were referred to the Department of Urogynaecology because of vaginal erosion after suburethral sling insertion for urinary stress incontinence. For evaluation of sexual function, all patients filled in an FSFI questionnaire before intervention and at follow-up. All patients underwent gynaecological examination including colposcopy, and the site and size of the defect were noted. INTERVENTION: The edge of the vaginal epithelium was trimmed, mobilized, and closed with interrupted vertical Vicryl mattress sutures in a single layer. MEASUREMENTS: FSFI questionnaire and clinical findings. RESULTS AND LIMITATIONS: Twenty-one patients were included in the study. Eighteen patients with larger defects were operated on, and three defects healed after topical application of estrogen cream. In 16 patients, the defect had healed at follow-up; two patients with persisting defects were brought back to surgery and the procedure was repeated, paying particular attention to tension-free adaptation of vaginal tissue. In one patient, partial sling removal was performed after the second failed intervention. The domains of desire (p<0.0001), arousal (p<0.0003), lubrication (p<0.0001), satisfaction (p<0.0130), and pain (p<0.0001) improved significantly. Orgasm remained unchanged (p=0.4130; all two-tailed t-test). CONCLUSION: Suburethral erosion can be treated effectively by resuturing. Sexual function is improved in regard to desire, arousal, lubrication, satisfaction, and pain, but not orgasm. In septic patients and patients with a history of radiation, grossly infected tissue, or severe pain, excision of the mesh needs to be considered.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

OBJECTIVE The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.