Sophie Françoise Mauricette Derchain

Prevalência do HPV em mulheres rastreadas para o câncer cervical

OBJECTIVE To assess the prevalence of high-risk genital human papillomavirus (HPV) infection by age group and risk factors associated. METHODS Cross-sectional study in a sample of 2,300 women (15-65 years old) who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. An epidemiological questionnaire was applied and cervical specimens were obtained for cytology and hybrid capture II test (HCII) for HPV detection. Statistical analysis included Pearson Chi-square and unconditional multiple logistic regression model (forward likelihood ratio). RESULTS High-risk genital HPV infection prevalence in this sample was 17.8% and age distribution was as follows: 27.1% (<25 years), 21.3% (25-34 years), 12.1% (35-44 years), 12.0% (45-54 years) and 13.9% (55-65 years). Subjects with the highest number of lifetime sexual partners had the highest rates of genital HPV infection. To be living with a partner, aged 35 to 44 years, and former smokers were protective factors. High-risk genital HPV infection was 14.3% in normal cytology, 77.8% in high grade squamous intraepithelial lesions and in the two cases (100%) of cervical cancer. CONCLUSIONS High-risk HPV prevalence was high in the sample studied. The highest prevalence of HPV infection was seen in women under 25 years old and then a new increase was seen over the age of 55 and the highest rates were found among those with many sexual partners during their lifetime.

Prognostic significance of PD-L1 and PD-L2 in breast cancer

PD-L1 and PD-L2 constitute an important antitumor immune response. In breast cancer, their prognostic value is still to be defined. In this study, we investigate the correlation between PD-L1 and PD-L2 protein expressions with clinical and pathologic features and disease-free survival and overall survival. To assess PD-L1 and PD-L2 expressions, we conducted immunohistochemistry studies using a breast cancer tissue microarray encompassing a total of 192 breast cancer cases, stages I, II, and III, with detailed clinical and outcome data. PD-L1 expression was present in 56.6% (107/189), and PD-L2 expression was identified in 50.8% (97/191) of breast cancer cases. Younger age at diagnosis, lymph node positivity, negative estrogen receptor, and recurrence at distant sites were all associated with both PD-L1 and PD-L2 expressions. The presence of larger tumors was associated only with PD-L1 expression. In our study, PD-L1 expression was significantly associated with better overall survival (P = .04) in breast cancer patients. Despite its association with poor clinical and pathologic features, PD-L1 expression emerges as a positive prognostic biomarker in breast cancer. This survival result might be due to the presence of a strong antitumor immune response leading to PD-L1 expression.

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, lifetime 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.

Risk-of-Malignancy Index in preoperative evaluation of clinically restricted ovarian cancer

CONTEXT There is no adequate preoperative method for differentiating between benign and malignant pelvic masses. Evaluations of CA 125 serum levels, ultrasonography findings and menstrual state have been tested in isolation as diagnostic methods. The evaluation of these three methods in association with each other could improve diagnostic performance. OBJECTIVE To evaluate the risk-of-malignancy index by combining serum CA 125 levels, ultrasound score and menopausal status in preoperative diagnoses for women with pelvic masses clinically restricted to the ovaries and without clear evidence of malignancy. DESIGN Cross-sectional study. SETTING Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil. PARTICIPANTS 158 women admitted between January 1996 and March 1998 for surgical exploration of pelvic masses. PROCEDURES The risk-of-malignancy index was calculated as US x M x CA 125, performed preoperatively. Ultrasound findings were classified according to the shape, size, multiplicity, presence of wall expansion involvement or ascites, using a score system (US). Menopausal status was considered as 1 for premenopausal and 3 for postmenopausal (M), and CA 125 serum levels were considered in absolute values. STATISTICAL ANALYSIS Most relevant variables were included in a logistic multiple regression model, fitted using the ultrasound score, the serum CA 125 level and the menopausal status. The model was used for evaluating the performance of each individual predictor in determining the malignancy of these tumors and identifying the risk-of-malignancy index. RESULTS The best individual performance was found in CA 125 levels (sensitivity of 78%, specificity of 75%), followed by ultrasound score (sensitivity of 75%, specificity of 73%) and menopausal status (sensitivity of 73%, specificity of 69%). The performance obtained for the risk-of-malignancy index at the cut-off point of 150 was a sensitivity and specificity of 79%. The area under the ROC curve for the risk-of-malignancy index was 0.90, which was greater than the area for CA 125 levels (0.83) or ultrasound score (0.79). CONCLUSION The risk-of-malignancy index using ultrasound morphological score, serum CA 125 levels and menopausal status might be of value in the preoperative assessment of ovarian carcinomas.

Conventional pap smear and liquid-based cytology as screening tools in low-resource settings in Latin America : Experience of the Latin American screening study

OBJECTIVE To evaluate the performance of the conventional Pap test and liquid-based cytology (LBC) in an ongoing multicenter trial testing optional screening tools (cytology, screening colposcopy, visual inspection with acetic acid, visual inspection with Lugols Iodine, cervicography and Hybrid Capture II [HCII] (Digene Brazil, São Paulo, Brazil) conventional and self-sampling), for cervical cancer in Brazil and Argentina. STUDY DESIGN A cohort of 12,107 women attending four clinics (Campinas, São Paulo, Porto Alegre, Buenos Aires) were randomized into the 8 diagnostic arms. Women testing positive with any of the tests were referred for colposcopy, and cervical biopsies were used as the gold standard to assess performance characteristics of the diagnostic tests. Conventional Pap smears were sampled by all clinics (n = 10,240), and LBC (Autocyte PREP, [TriPath Imaging, Burlington, North Carolina, U.S.A.], n=320, and DNA-Citoliq [Digene Brazil], n =1,346) was performed by 1 of the clinics. RESULTS Conventional Pap smears showed no squamous intraepithelial lesions (normal) in 8,946 (87.4%) and LBC in 1,373 (82.4%). Using high grade squamous intraepithelial lesions (HSIL) as the cutoff, Pap smears predicted high grade (cervical intraepithelial neoplasia [CIN] 3) with OR 63.0 (95% CI, 36.90-107.70), standard error (SE) 59%, SP 97.8%, positive predictive value (PPV) 68.1% and negative predictive value (NPV) 96.7%. The same figures for Autocyte PREP were: OR 9.0 (95% CI, 2.43-33.24), sensitivity (SE) 33.3%, specificity (SP) 100%, PPV 100% and negative PV (NPV) 88.8%. DNA-Citoliq detected CIN 3 as follows: OR 11.8 (95% CI 2.60-53.26), SE 40.0%, SP 94.6%, PPV 40.0% and NPV 94.6%. Lowering the cutoff to low grade squamous intraepithelial lesions increased SE and NPV but compromised SP and PPV. The detection rates for high grade lesions after an atypical squamous cells of undetermined significance diagnosis were similar with the 3 techniques. In our settings, the 3 methods of cervical cytology were slightly different in performance. The conventional Pap smear had the highest SE, while Autocyte PREP had 100% SP and PPV in detecting CIN3 with the HSIL cutoff. All 3 tests had lower SE but higher SP as compared to HCII.

Human papillomavirus viral load in predicting high-grade CIN in women with cervical smears showing only atypical squamous cells or low-grade squamous intraepithelial lesion

CONTEXT Human papillomavirus (HPV) viral load may have an important role in predicting high-grade cervical intraepithelial neoplasia (CIN) in women with cervical smears showing atypical squamous cells or LSIL. OBJECTIVE To determine whether the assessment of the viral load of high-risk HPV DNA is useful in predicting the detection of high-grade cervical intraepithelial neoplasia (CIN2 and 3) in women referred because of cervical smears showing only atypical squamous cells or LSIL. TYPE OF STUDY Cross-sectional. SETTING Colposcopy Clinic in a University hospital. METHODS A series of 119 women referred because of atypical squamous cells or LSIL between August 2000 and April 2001 were included. All women were subjected to a new cervical smear, HPV testing for the high-risk types using hybrid capture II (HCII), viral load measurement in relative light units (RLU) and colposcopy, with cervical biopsies (n = 97). Cervical lesions were graded using the CIN classification. RESULTS Cervical biopsies revealed CIN2 or CIN3 in 11% of the cases, equally among women referred because of atypical squamous cells or LSIL. The HCII test was positive in 16% of women with atypical squamous cells and 52% of those with LSIL (OR = 5.8; 95% CI 1.4 to 26.7). There was strong correlation between CIN2 or CIN3 and positivity for HPV DNA when this group was compared with women with only CIN1 or normal cervix (OR = 7.8; 95% CI 1.5 to 53.4). In ROC analysis for HCII in diagnosing CIN2 and CIN3, the area under the ROC curve was 0.784, and the viral load cutoff point of 10.0 RLU/cutcuff presented 77% sensitivity and 73% specificity. Second cytology showing at least atypical squamous cells did not accurately detect CIN2 or CIN3 (OR = 6.4; 95% CI 1.0 to 50.9). The sensitivities of the second cervical smear and HCII were similar, although the specificity of HCII was significantly higher than the second cervical smear. CONCLUSIONS The viral load of high-risk HPV types was significantly associated with the diagnosis of CIN2 or CIN3 in women referred because of atypical squamous cells and LSIL abnormalities in their cervical smear.

Ultrasound criteria and CA 125 as predictive variables of ovarian cancer in women with adnexal tumors

To evaluate the capacity to predict malignancy in women with adnexal tumors using CA 125 measurement and ultrasound criteria.

Prevalence of human papillomavirus infection and associated risk factors in young women in Brazil, Canada, and the United States: a multicenter cross-sectional study.

To determine the prevalence of cervical human papillomavirus (HPV) infection and risk factors in young women from Brazil, Canada, and the USA. Cross-sectional study in 3204 healthy women, aged 15 to 25 years. Cervical samples were collected for cytology and for HPV DNA detection (SPF10-LiPA25 system). Serum samples were collected for the measurement of HPV-16 and HPV-18 antibodies by enzyme-linked immunosorbent assay. Risk factors were obtained through a questionnaire. Overall, 26.6% of women had DNA detected for at least 1 HPV type. The prevalence for oncogenic HPV types was 21.7% (25% in Brazil, 16.9% in Canada, and 19.1% in the USA). HPV-16 was the most prevalent oncogenic type (5.2%). The next most common oncogenic HPV types were 51 (3.3%), 52 (3.3%), 31 (2.9%), 66 (2.3%), and 39 (2.0%). Multiple oncogenic types were detected in one-third of the infections. The prevalence of HPV-16 and/or HPV-18 infections detected by DNA and/or enzyme-linked immunosorbent assay was 24.8%. The majority of women (85%) had a normal cervical cytology. Sexual behavior was the main determinant for HPV-16/18 infections and squamous intraepithelial lesions. The prevalence of HPV oncogenic infections was high and linked to sexual behavior. Strategies to reduce the burden of oncogenic HPV infection, such as prophylactic vaccination programs, are likely to impact the burden of disease due to cervical precancer and cancer.

Serological detection of anti HPV 16/18 and its association with pap smear in adolescents and young women

OBJECTIVE Verify the relation between HPV 16/18 antibodies and the association with cervical cytology findings in adolescents and young women. METHODS A cross sectional study with 541 healthy and sexually active women from 15 to 25 years of age was carried on from September to November 2000. At gynecological examination, a cervical sample on liquid-base for cytology-testing and a blood sample for ELISA identification of HPV 16 and 18 antibodies were collected and sent to a reference laboratory in Belgium. Statistical analysis estimated the prevalence and prevalence ratio with a 95% confidence interval. RESULTS Of these young women, 150 (27.7%) were seropositive: 79 (14.6%) to HPV 16 antibody; 35 (6.4%) to HPV 18 antibody and 36 (6.6%) to both HPV 16/18 antibodies. Cytological abnormalities were detected in 107 cases (20.5%): 63 presented with atypical squamous cells of undetermined significance (ASCUS), 41 were suggestive of low grade squamous intra-epithelial lesion (LGSIL) and 3 of high grade squamous intra-epithelial lesion (HGSIL). Prevalence of abnormal cytology with a positive serology was only 1.75 times that of prevalence of abnormal cytology with a negative serology. Detection of abnormal cytology was not correlated with positive serology. CONCLUSION Results of this study indicate a high prevalence of HPV 16 and 18 in young healthy women which showed no relation to the abnormal findings of cytology smears.

Neoplasia intra-epitelial cervical: diagnóstico e tratamento

Cervical cancer is nowadays a disease amenable to secondary prevention. Methods for the detection of its precursor lesions and human papillomavirus infection, such as cervical cytology and molecular biology, achieved widespread use worldwide. However, there is still too much controversy regarding the use of these methods in gynecological practice. Which is the best examination or the best association of examinations, and the most adequate time intervals to proceed with screening, are still pending questions, generating anxiety in patients and doctors. On the other hand, the management of women who have been diagnosed with viral infection and/or cervical intraepithelial neoplasia is not yet consensual, and several factors may affect the clinical decision on how to treat them. Therapeutic options are dependent upon the type of viral infection, severity of the cervical intraepithelial neoplasia and its histological type. The aim of the present article was to review the several aspects of cervical cancer screening and its viable treatment.