Safety of screening with Human papillomavirus testing for cervical cancer at three-year intervals in a high-risk population: experience from the LAMS study.

OBJECTIVES: To assess whether human papillomavirus (HPV) testing is a safe enough approach to warrant extension of the screening intervals of baseline Papanicolaou (Pap)-/HPV- women in low-income settings. METHODS: Of the >1000 women prospectively followed up as part of the Latin American Screening (LAMS) Study in São Paulo, Campinas, Porto Alegre) and Buenos Aires, 470 women with both baseline cytology and Hybrid Capture 2 (HC2) results available were included in this analysis. These baseline Pap-negative and HC2- or HC2+ women were controlled at six-month intervals with colposcopy, HC2 and Pap to assess the cumulative risk of incident Pap smear abnormalities and their predictive factors. RESULTS: Of the 470 women, 324 (68.9%) were high-risk HPV (hrHPV) positive and 146 (31.1%) were negative. Having two or more lifetime sex partners (odds ratio [OR] = 2.63; 95% CI 1.70-3.51) and women using hormonal contraception (OR = 2.21; 95% CI 1.40-3.51) were at increased risk for baseline hrHPV infection. Baseline hrHPV+ women had a significantly increased risk of incident abnormal Pap smears during the follow-up. Survival curves deviate from each other starting at month 24 onwards, when hrHPV+ women start rapidly accumulating incident Pap smear abnormalities, including atypical squamous cells (ASC) or worse (log-rank; P < 0.001), low-grade squamous intraepithelial lesions (LSIL) or worse (P < 0.001) and high-grade squamous intraepithelial lesions (HSIL) (P = 0.03). Among the baseline hrHPV- women, the acquisition of incident hrHPV during the follow-up period significantly increased the risk of incident cytological abnormalities (hazard ratio = 3.5; 95% CI 1.1-11.7). CONCLUSION: These data implicate that HPV testing for hrHPV types might be a safe enough approach to warrant extension of the screening interval of hrHPV-/Pap-women even in low-resource settings. Although some women will inevitably contract hrHPV, the process to develop HSIL will be long enough to enable their detection at the next screening round (e.g. after three years).

Drug addiction is not an independent risk factor for oncogenic human papillomavirus infections or high-grade cervical intraepithelial neoplasia: case-control study nested within the Latin American Screening study cohort.

Drug abuse (addiction) has been listed among the risk factors for human papillomavirus (HPV) infections, but no case-control studies exist to rule out sexual behaviour and other potential confounders. The aim of this study is to evaluate the role of drug addiction as an independent predictor of HR-HPV infections and (cervical intraepithelial neoplasia) CIN2+ in an age-matched case-control (1:4) study nested within the prospective Latin American Screening (LAMS) study cohort. All 109 women in the LAMS cohort (n=12,114) reporting drug abuse/addiction were matched with four controls (n = 436) of non-abusers strictly by age. Conditional logistic regression analysis was used to estimate the co-variates of drug abuse, and the whole series (n=545) was analysed for predictors of HR-HPV and CIN2+ using univariate and multivariate regression models. Oncogenic HPV infections were significantly (P=0.019) more prevalent among abusers (37.7%) than in controls (21.9%), but there was no difference in high-grade squamous intraepithelial lesions (P=0.180) or CIN2+ lesions (P=0.201). In multivariate conditional logistic regression, number of lifetime sexual partners (P=0.0001), ever smokers (P=0.0001), non-use of OCs (P=0.013), ever having sexually transmitted diseases (STD) (P=0.041) and no previous Pap smear (P=0.027) were independent co-variates of drug addiction. Drug abuse was not an independent risk factor of high-risk (HR)-HPV infection, which was significantly predicted by (1) age below 30 years (P=0.045), (2) more than five lifetime sexual partners (P=0.046) and (3) being current smoker (P=0.0001). In multivariate model, only HR-HPV infection was an independent risk factor of CIN2+ (P=0.031), with adjusted OR=11.33 (95% CI 1.25-102.50). These data indicate that drug addiction is not an independent risk factor of either HR-HPV infections or CIN2+, but the increased prevalence of HR-HPV infections is explained by the high-risk sexual behaviour and smoking habits of these women.

Primary screening for cervical cancer through self sampling.

OBJECTIVE: To evaluate the use of community health agents (CHAs) to instruct women living in poor rural areas in obtaining self-collected cervical samples and compare the high-risk HPV (hrHPV) hybrid capture (HC) results obtained to those for gynecologist-collected samples. METHODS: After a one-day training, CHAs visited sexually active women, instructing each in the use of collection brush and the Universal Collection Medium tube. One week thereafter, a gynecologist collected cervical samples from, and performed colposcopies on, the same women. A single reference lab performed all HCs. RESULTS: 878 women (Age: 15-69 years) participated. Among self-collected samples, hrHPV prevalence was 33.9% (95% CI: 30.8%-37%), compared with 28.6% (95% CI: 27%-30%) among gynecologist-collected samples. However, 9.3% of the patients were HPV HC II-positive in the self-collected sample and HPV HC II-negative in the gynecologist-collected samples (95% CI: 7.38%-11.22%), whereas 4% tested positive in gynecologist-collected samples and negative in self-collected samples (95% CI: 2.7%-5.3%) (P<0.01; kappa=0.7). Of 9 cases of histologically-confirmed, high-grade squamous intraepithelial lesion, self-collected and provider-collected samples missed one each. CONCLUSION: Self-collected vaginal sampling could be made an additional CHA function under existing program conditions, improving access to cervical cancer screening in poor rural settings.

Performance of the DNA-Citoliq liquid-based cytology system compared with conventional smears.

OBJECTIVE: To evaluate the performance of a new, manual, simplified liquid-based system, DNA-Citoliq (Digene Brasil), employed under routine conditions as compared to conventional smears collected from six collaborating private laboratories. METHODS: A panel of cytopathologists, who served as the gold standard diagnosis, adjudicated discordant opinions. RESULTS: Of 3206 pairs of slides considered valid for comparison, there were 3008 in full agreement (93.8%), 112 (3.5%) with one diagnostic category discrepancies, and 86 (2.7%) discordant cases. Among the 288 borderline+ by either method, DNA-Citoliq detected abnormalities in 243 (84.4%), and conventional smears (CS) detected abnormalities in 178 (61.8%) (McNemar test, P < 0.000), a 36.5% increased detection of borderline+ cases. CONCLUSIONS: For mild dyskaryosis, DNA-Citoliq detected 176 cases and CS 125 cases (McNemar test, P < 0.000); and for moderate+severe dyskaryosis 66 versus 32 cases respectively (McNemar test, P < 0.000).

Evaluation of visual inspection with acetic acid (VIA), Lugol's iodine (VILI), cervical cytology and HPV testing as cervical screening tools in Latin America. This report refers to partial results from the LAMS (Latin AMerican Screening) study.

OBJECTIVES: To assess the performance indicators of visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI) in four Latin American centres participating in the ongoing Latin AMerican Screening (LAMS) study, in settings with moderate incidence of cervical disease and with poorly to moderately well-organized cervical cancer screening. SETTING: Three Brazilian centres (São Paulo, Campinas and Porto Alegre) and one Argentine centre (Buenos Aires) recruited a total of 11,834 healthy women to undergo VIA, VILI, conventional Pap smear and Hybrid Capture II (HCII). METHODS: Women who had a positive result from any of these tests were subjected to colposcopy and biopsies (if necessary), and women with high-grade cervical intraepithelial neoplasia (CIN) were properly treated. To control for verification bias, 5% of women with normal tests were referred for colposcopy, as were 20% of HCII-negative women. RESULTS: Data on VIA (n=11,834), VILI (n=2994), conventional Pap smear (n=10,138) and HCII (n=4195) were available for test comparisons, calculating sensitivity, specificity, and positive and negative predictive values. Overall test positivity was 11.6% for VIA, 23.0% for VILI, 2.2% for Pap smear (LSIL threshold), 1.1% for Pap smear (HSIL threshold) and 17.1% for HCII. VIA was positive in 61.8% of the women with CIN 1, 57.0% of those with CIN 2, 35.0% of women with CIN 3 and in 21 of 28 (75%) of women with cancer. Approximately 10% of women with no detectable disease had an abnormal VIA. Regarding VILI, 83.3% of women diagnosed with CIN 1 and 62.5% of those with CIN 3 had an abnormal test. VILI failed to detect one of three cases of cancer. Both the sensitivity, specificity and positive predictive value of VIA and VILI in detecting CIN 2 or CIN 3 could be significantly improved depending on the combination with Pap smear or HCII (sensitivity up to 100.0% and specificity up to 99.8%). CONCLUSIONS: The LAMS study failed to reproduce the performance figures obtained with VIA and VILI (as stand-alone tests) in some other settings, where the prevalence of cervical disease was higher. However, a combined use of VIA or VILI with the Pap test or HCII allowed specific detection of cervical abnormalities.

Comparing PAP smear cytology, aided visual inspection, screening colposcopy, cervicography and HPV testing as optional screening tools in Latin America. Study design and baseline data of the LAMS study.

OBJECTIVES: This is a European Commission (EC)-funded ongoing study known as the LAMS (Latin American Screening) study, where PAP smear/liquid-based cytology and screening colposcopy were compared with i) three optional screening tools [visual inspection with acetic acid (VIA), or Lugol's iodine (VILI), cervicography] and with ii) Hybrid Capture II from a) conventional samples and from b) self-samples, in women at different risk for cervical cancer in Brazil and Argentina. STUDY DESIGN: During 2002-2003, a cohort of 12,107 women attending four clinics: Campinas (CA), Sao Paulo (SP), Porto Alegre (PA) and Buenos Aires (BA), were interviewed for risk factors, and examined using the 8 diagnostic arms. Colposcopy was performed for women positive in any test and for 5% of women with baseline PAP-negative and 20% of HCII-negatives. All high-grade lesions (CIN2/3) were treated, and low-grade CIN are prospectively followed-up. RESULTS: Of the 12,107 women, the following baseline data are available: epidemiological data (n=11,996), conventional PAP smears (n=10,363), LBC, SurePATH (n=320), LBC, DNA-Citoliq (n=1,346), VIA (n=12.067), VILI (n=3,061), cervicography (n=279), screening colposcopy (n=3,437), HCII conventional (n=4,710), HCII self-sampling (n=246) and cervical biopsies (n=1,524). The four sub-cohorts differ significantly in all their baseline data on the implicated risk factors of cervical cancer, consonant with their origin from regions with different cancer incidence. Around 95% of all PAP smears were negative, with slight variations in the prevalence of LSIL and HSIL between the four centers. Significant differences were found in the detection rates of abnormal findings in VIA, VILI and colposcopy between the four centers (p=0.0001). The prevalence of HPV was practically identical (16.5-18.8%) in all four cohorts (p=0.486), with no differences in the relative viral loads. Biopsy results were different depending on whether the women underwent screening colposcopy (BA) or elective colposcopy (others). CONCLUSION: Four cohorts with significantly different baseline data are available, and prospective follow-up of these women permits analysis of whether variations in cervical cancer incidence in these regions is due to i) different natural history of the precursor lesions, or ii) due to different levels of exposure to the known risk factors.

Histologic studies of the effects of circulating hot saline on the uterus before hysterectomy.

STUDY OBJECTIVE: To evaluate a new device for endometrial ablation. DESIGN: (Canadian Task Force classification II-1). SETTING: University-affiliated hospital. PATIENTS: Thirty-two women scheduled for hysterectomy. INTERVENTIONS: Endometrial ablation and hysterectomy. MEASUREMENTS AND MAIN RESULTS: The new device for endometrial ablation was evaluated by studying depth of necrosis after staining for the oxidative enzyme NADH. Uniform endomyometrial necrosis was achieved at a depth of 2 to 4 mm with 90 degrees C saline circulated for 10 minutes. CONCLUSION: The procedure was successful in all patients, and there were no adverse clinical sequelae. (J Am Assoc Gynecol Laparosc 6(3):269-273, 1999)

Evaluation of Hydro ThermAblator for endometrial destruction in patients with menorrhagia.

OBJECTIVE: To describe endometrial destruction with the Hydro ThermAblator. DESIGN: (Canadian Task Force classification II-1). SETTING: University-affiliated hospital. PATIENTS: Twenty-six women with uncontrolled menorrhagia. INTERVENTION: Endometrial ablation with saline heated to 90 degrees C and circulated in the uterine cavity for 10 minutes under hysteroscopic control. MEASUREMENTS AND MAIN RESULTS: All patients tolerated the procedure well, all but one was satisfied with the results, and there were no significant side effects or complications. Seventy-seven percent of women were either amenorrheic or hypomenorrheic after 6 months, and 88% were amenorrheic or hypomenorrheic after 1 year, including one patient who was treated a second time; 87.5% were amenorrheic or hypomenorrheic at 18 months. One woman had persistent menorrhagia and was treated by hysterectomy. CONCLUSION: In this study, endometrial ablation was performed successfully with the Hydro ThermAblator in 25 of 26 women. (J Am Assoc Gynecol Laparosc 6(3):275-278, 1999)

[Treatment of human papillomavirus infection of the uterine cervix with gel interferon]. / Tratamento da infecção do colo uterino por papilomavírus humano com interferon gel.

Treatment of uterine cervix infection caused by human papillomavirus still is an enigma. Some drugs have been tested with cure rates between 60 to 70%. Most of such agents are substances which produce a strong epithelial desquamation and have shown strictly toxic side effects. The use of interferon in this infection has been studied, but different authors disagree in their therapeutic findings. A randomized, double blind trial was conducted to compare interferon to placebo. Preliminary results are presented in this article. 47 patients were followed so far. 18 of them were evaluated and the results are shown in this article.

[Diagnosis of cervicovaginal infection by human papillomavirus. Value of colposcopy, cytology and histopathology as methods of diagnosis]. / Diagnóstico da infecção cervicovaginal por papilomavírus humanos. Valor da colposcopia, citologia e da histopathologia como métodos diagnósticos.

The authors evaluated 476 patients to determine the accuracy of colposcopy, cytology, and histopathology as diagnostic methods for cervical and vaginal HPV infections. Results were treated by statistical analysis which showed significant disagreement among the methods tested. Colposcopy was positive in 87.8% of the cases. Abnormal transformation zone was the most frequent finding in the cervix, acetowhite epithelium being its main representative. Condylomatous vaginitis was the most frequent feature in the vaginal surface. Cytology was positive in 76.9% of the cases. To increase sensitivity of this method, the authors suggest that not only koilocytosis is important, but other major aspects are also important, such as minimal koilocytosis, dyskeratosis, karyopyknosis, binucleation, and multinucleation. Histopathology was positive in 81.9% of the cases. In conclusion, the three diagnostic methods studied presented statistical disagreement, however, they are supplementary and efficient.