Cervical Intraepithelial Neoplasia In Women Research Articles

Lower Risk of Cervical Intraepithelial Neoplasia in Women with High Plasma Folate and Sufficient Vitamin B12 in the Post-Folic Acid Fortification Era

The purpose of this study was to determine the influence of plasma folate and vitamin B12 concentrations on cervical cancer risk in the U.S. after the folic acid fortification era. The study included 376 premenopausal women of childbearing age who tested positive for infections with high-risk (HR) human papillomaviruses (HPVs) and were diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN 2+, cases) or <or=CIN 1 (noncases). CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified plasma folate concentrations combined with plasma B12 concentrations as the independent predictors of primary interest, adjusting for age, race, education, smoking, parity, number of life-time male sexual partners, use of contraceptives, waist circumference, physical activity, healthy eating index, and circulating concentrations of vitamins A, C, tocopherol, and total carotene. Women with supraphysiologic concentrations of plasma folate (>19.8 ng/mL) who also had sufficient plasma vitamin B12 (>or=200.6 pg/mL) had 70% lower odds of being diagnosed with CIN 2+ (P = 0.04) when compared with women with plasma folate of <or=19.8 ng/mL and plasma vitamin B12 of <200.6 pg/mL. Our results do not corroborate the concern that supraphysiologic plasma folate concentrations seen in the post-U.S. folic acid fortification era increase the risk of CIN in premenopausal women of childbearing age. In fact, higher folate is associated with significantly lower risk of CIN, especially when vitamin B12 is sufficient, demonstrating the importance of vitamin B12 in the high-folate environment created by the folic acid fortification program.

Clinical performance of Abbott RealTi me High Risk HPV test for detection of high-grade cervical intraepithelial neoplasia in women with abnormal cytology

Abbott RealTime High Risk (HR) HPV is a recently developed test for the detection of 14 high-risk oncogenic HPV types combined with the ability to concurrently identify genotypes 16 and 18. The clinical performance of the Abbott RealTime HR HPV test was evaluated in comparison with the Hybrid Capture 2 (HC2) test for the detection of cervical intraepithelial neoplasia 2 or worse (CIN2+). The relative accuracy of the Abbott RealTime HR HPV to detect high-risk HPV was also determined. Cervical specimens were collected from 702 patients with abnormal cytology who were referred for colposcopy, and were tested with liquid based cytology (LBC), Abbott RealTime HR HPV and HC2. Genotyping was done using the Linear Array (LA) method. Histological assessment was used as the gold standard for disease status. Clinical performance for detection of disease was evaluated for Abbott RealTime HR HPV in comparison with HC2 in the overall population and in each cytological grade. The relative accuracy for detection of high-risk HPV was assessed by concordance between the two tests and based on LA genotyping. The Abbott RealTime HR HPV showed similar clinical performance for detection of CIN2+ when compared with HC2, for both the overall population and those with a cytological grade of atypical squamous cells of undetermined significance (ASC-US). The accuracy for detection of high-risk HPV was significantly higher with Abbott RealTime HR HPV than with HC2.

Smoking worsens the prognosis of mild abnormalities in cervical cytology

To examine the effect of smoking on the incidence of low- and high-grade cervical intraepithelial neoplasia (CIN) in women with a baseline Pap smear of atypical squamous cells (ASC) or a low-grade squamous intraepithelial lesion (LSIL). Prospective study in which a cohort of women with normal colposcopy and ASC/LSIL at baseline were followed at 6-month intervals of up to 36 months. Women were grouped in post-hoc analysis according to their smoking behavior: never (or past) smokers and current smokers. This report was based on data from the Latin American Screening Study, conducted in Sao Paulo, Campinas, Porto Alegre (Brazil) and Buenos Aires (Argentina). A subset of 150 women derived from a cohort of 1,011 women. Multivariate Cox analysis and Kaplan-Meier curves were used. Low- and high-grade CIN during follow-up. The only factor related to an increased risk of developing CIN was the positive high-risk (hr) HPV status (hazard ratio (HR) = 3.42; 95% CI: 1.11-9.43). A total of 21 cases of incident CIN were detected during follow-up. Of these, 11 appeared in the group of 67 smokers and 10 among the 83 non-smoker women (log-rank, p=0.33). Smoking status was not associated with the risk of developing CIN (HR = 0.73; 95% CI: 0.40-1.33). However, when restricting the analysis to high-grade CIN only (11 cases), the probability of developing the disease was significantly higher among smokers (p=0.04). Smoking contributes additional risk for developing high-grade CIN in women with ASC or LSIL cytology but normal colposcopy.

Phylogenetic classification of human papillomavirus genotypes in high-grade cervical intraepithelial neoplasia in women from a densely populated Brazilian urban region.

Differences in human papillomavirus (HPV) types may correlate with the biological potential and invasion risk of high-grade cervical intraepithelial neoplasia (CIN 2 and CIN 3). The objective of this study was to determine the relationship between different combinations of HPV types and CIN severity. Cross-sectional study, at Universidade Estadual de Campinas (Unicamp). Cervical samples from 106 women treated due to CIN 2 (18) or CIN 3 (88) were examined for specific HPV genotypes using Roche Linear Array (LA-HPV). The proportions of CIN 2 and CIN 3 in groups of women infected with the HPV phylogenetic groups A7 and A9 were compared. Three groups were formed: women with single infections; multiple infections; and the whole sample. Multiple infections were detected in 68 samples (64.7%). The most frequent high-risk genotypes detected (single/multiple) were HPV 16 (57.1%), HPV 58 (24.7%), HPV 33 (15.2%), HPV 52 (13.3%), HPV 31 (10.4%), HPV 51 (7.6%) and HPV 18 (6.6%). Women without infection with HPV species Alpha 9 were less likely to have CIN 3 than were their Alpha 9 HPV-infected counterparts. HPV 16 and/or HPV 18, with or without associations with other viral types, were more frequently found in women with CIN 3 than in those with CIN 2. The severity of high-grade CIN may be aggravated by the presence of HPV types included in the Alpha 9 phylogenetic classification and by infections including HPV 16 and 18, singly or in combination with other HPV genotypes.

The Diagnostic Accuracy of Colposcopy in Previously Treated Cervical Intraepithelial Neoplasia

To determine whether colposcopy is reliable in diagnosing cervical intraepithelial neoplasia in women who have undergone a previous cervical excision biopsy. A prospective study of women attending the colposcopy clinic at the University Hospital of North Staffordshire was performed between January 1998 and December 1999. A clear histological diagnosis of the grade of cervical intraepithelial neoplasia was available for 469 in the treatment-naive group and 58 in the treatment group. kappa coefficients comparing the colposcopic impression (negative, low-grade, high-grade, or invasion) with histological diagnosis showed that there was no difference between the treatment-naive group, weighted kappa=0.46, and the previous treatment group, weighted kappa=0.47. The sensitivity, specificity, positive predictive value, and negative predictive value of colposcopy for any cervical disease in the treatment-naive women were 93.9%, 51.9%, 96.7%, and 34.1%, respectively, compared with 77.6%, 66.7%, 86.4%, and 35.3% in previously treated women. The sensitivity of colposcopy fell when it was used to differentiate normal and low-grade disease from high-grade disease and invasion: 82.4%, 55.9%, 82.6%, and 49.6% for treatment-naive women, compared with 61.5%, 84.2%, 60.0% and 51.6%, respectively, for the previous treatment group. Previous treatment to the cervix does not seem to impair the ability of colposcopy to differentiate normal cervix from all grades of cervical abnormality in women where the squamocolumnar junction is visible. However, there is a suggestion that the sensitivity of colposcopy to differentiate negative/low-grade disease from high-grade disease/invasion is lower in previously treated women.

Epidemiological survey of high risk factors for cervical intraepithelial neoplasia in women

One hundred and twenty-two patients with confirmed cervical intraepithelial neoplasia (CIN), as a result of occasional screening for uterine cervix cancer in our out-patient clinic between July 2006 and August 2007, and 122 control patients with cervicitis who received colposcopy during the same period were enrolled in this study. Our results showed that 72% participants didn't receive uterine cervix cancer screening during the past 2 years; 55% women had premarital sexual behavior. CIN was most commonly seen in 30 to 34 year old women. Occasional screening could identify 75% CIN. In comparison with the control group, the incidence of earlier first sexual behavior, marriage, and delivery, multiple pregnancy, and frequent abortion was significantly increased in the study group (P < 0.05). We suggest that increased access to uterine cervix cancer screening might be more important than technical improvement. Key words: Cervical intraepithelial neoplasia; Risk factors

Comparison of Predictors for High-Grade Cervical Intraepithelial Neoplasia in Women with Abnormal Smears

The detection of high-risk human papillomavirus (HPV) DNA provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). This study compared the sensitivity and specificity of several adjunctive tests for the detection of high-grade CIN in a population referred to colposcopy because of abnormal cytology. 953 women participated in the study. Up to seven tests were carried out on a liquid PreservCyt sample: Hybrid Capture II (Digene), Amplicor (Roche), PreTect HPV-Proofer (NorChip), APTIMA HPV assay (Gen-Probe), Linear Array (Roche), Clinical-Arrays (Genomica), and CINtec p16INK4a Cytology (mtm Laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology seen on either the biopsy or the treatment specimen after central review. 273 (28.6%) women had high-grade disease (CIN2+) on worst histology, with 193 (20.2%) having CIN3+. For the detection of CIN2+, Hybrid Capture II had a sensitivity of 99.6%, specificity of 28.4%, and PPV of 36.1%. Amplicor had a sensitivity of 98.9%, specificity of 21.7%, and PPV of 33.5%. PreTect HPV-Proofer had a sensitivity of 73.6%, specificity of 73.1%, and PPV of 52.0%. APTIMA had a sensitivity of 95.2%, specificity of 42.2%, and PPV of 39.9%. CINtec p16INK4a Cytology had a sensitivity of 83.0%, specificity of 68.7%, and PPV of 52.3%. Linear Array had a sensitivity of 98.2%, specificity of 32.8%, and PPV of 37.7%. Clinical-Arrays had a sensitivity of 80.9%, specificity of 37.1%, and PPV of 33.0%.

Is Atypical Squamous Cells That Cannot Exclude High-Grade Squamous Intraepithelial Lesion Clinically Significant?

Upwards of 50 million women in the United States are screened each year in order to identify the relatively few who have significant preinvasive cervical disease, grade 2 or 3 cervical intraepithelial neoplasia (CIN), or cancer. The Bethesda 2001 System distinguishes between atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells that cannot exclude a high-grade squamous intraepithelial lesion (ASC-H). Colposcopy is recommended for women having ASC-H. This retrospective study attempted to determine the cumulative risk of CIN 2 or 3 in patients with ASC-H. The study population consisted of 229 patients with ASC-H whose mean age was 33 years. Initial assessment included colposcopy, endocervical curettage, and ectocervical biopsy as indicated. At the time of initial colposcopy, 10% of women had histological evidence of CIN 2 or 3. More than 80% of lesions were identified by ectocervical biopsy. All affected women underwent electrosurgical loop excision. Of those women with normal initial findings, 134 had repeat colposcopy with liquid-based cytology after 6 months and 5 of them (3.7%) proved to have CIN 2 or 3. None of 59 patients who had normal findings at 6 months had histological evidence of CIN when reevaluated at 12 months. The cumulative risk of CIN 2 or 3 after 12 months was 12.2%. Using any grade of CIN as the clinical end point, the cumulative rate was 27.9%. Of those women with initially normal findings who had high-grade CIN discovered during follow-up, about 80% had low-grade squamous intraepithelial lesion or normal cytology. The frequency of CIN 2 or 3 in these women with ASC-H was lower than previously reported rates. If future studies confirm a low rate of CIN in women with ASC-H, it might be appropriate to employ other parameters in order to decide which patients require colposcopy. It might also prove helpful to combine patients having ASC-US and those with ASC-H into a single diagnostic category.

Human Papillomavirus Type–Specific 18-Month Risk of High-Grade Cervical Intraepithelial Neoplasia in Women with a Normal or Borderline/Mildly Dyskaryotic Smear

High-risk human papillomavirus (hrHPV) DNA testing is an increasingly used instrument in cervical cancer prevention along cervical cytology. The inclusion of hrHPV testing in cervical screening requires efficient management as many hrHPV infections are transient. We investigated the potential value of hrHPV genotyping in normal and borderline/mildly dyskaryotic (BMD) smears. From a screening population of 44,102 women in the Netherlands, we included hrHPV-positive women with a normal or BMD smear. We assessed the type-specific 18-month risk of high-grade cervical intraepithelial neoplasia (CIN). In hrHPV-positive women, 18-month risk of CIN grade 3 or invasive cancer (> or =CIN3) was 6% [95% confidence interval (95% CI), 4-9] after normal cytology and 20% (95% CI, 16-25) after BMD. If positive for HPV16, > or =CIN3 risks were 14% (95% CI, 9-21) and 37% (95% CI, 28-48), respectively. In the subset of hrHPV-positive women without HPV16, HPV18 was associated with an increased risk of high-grade CIN after normal cytology and HPV31 and HPV33 were associated with an increased risk, particularly after BMD. HPV16 and HPV18 were also associated with an increased risk of high-grade CIN in women with an hrHPV-positive normal baseline smear and a repeat normal smear at 6 months. HrHPV-positive women without type 16, 18, 31, or 33 had a relatively low risk of high-grade CIN. Among women with baseline normal cytology and among women with a baseline and repeat normal smear, HPV16/18-positive women showed an increased risk of high-grade CIN. This warrants more aggressive management of HPV16/18-positive women compared with other hrHPV-positive women.

Use of p16INK4a Cytology as a Triage Tool for the Detection of High-grade Cervical Intraepithelial Neoplasia in Women with Atypical Squamous Cells of Undetermined Significance or Low-grade Squamous Intraepithelial Cell Cytology

Wentzensen, N.; Bergeron, C.; Cas, F.; Vinokurova, S.; Doeberitz, M. von Knebel Author Information

Evaluation of an Enzyme-linked Immunosorbent Assay-based p16INK4a Detection Assay for the Identification of High-grade Cervical Intraepithelial Neoplasia in Women Attending a Cervical Dysplasia Outpatient Clinic

Wentzensen, N.; Hampl, M.; Herkert, M.; Reichert, A.; Trunk, M.; Ridder, R.; von Knebel Doeberitz, M. Author Information

Topografia śródnabłonkowej neoplazji (CIN) na szyjce macicy

Topografia śródnabłonkowej neoplazji (CIN) na szyjce macicy

Papilomavirus y Factores asociados a Neoplasia Intraepitelial Cervical de Alto Grado en Cauca, Colombia

Evaluating the role of the main factors associated with high-risk cervical intraepithelial neoplasia in women from the Cauca Department in Colombia. After signing a consent-form, women were interviewed to obtain socio-demographic and lifestyle data. A cervical biopsy was performed on each woman for histopathological diagnosis (cases) and a sample of exfoliated cells (cases and controls) to extract DNA for HPV detection by polymerase chain reaction. A total of 98 cases and 109 controls, matched by age and ethnicity, were recruited for the study. The study confirmed association between HPV and the risk of cervical neoplasia (OR = 19.0; 95% CI = 8.20-44.2). The data suggested that multiparity (OR = 4.1; 95% CI = 1.62-10.6) and exposure to carcinogens present in wood-smoke (OR = 7.3; 95% CI = 3.00-19.4) are important co-factors for cervical neoplasia given the presence of HPV. These results provide valuable information for public health institutions to develop better cervical neoplasia prevention programmes.

Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.

Human Papillomavirus Testing (Hybrid Capture Ii) to Detect High-Grade Cervical intraepithelial Neoplasia in Women with Mildly Abnormal Papanicolaou Results

To evaluate the clinical value of human papillomavirus (HPV) DNA testing (Hybrid Capture II) in predicting which women with mild cervical cytologic abnormality (atypical squamous cells of undetermined significance [ASCUS] or low-grade squamous intraepithelial lesions [LSIL]) are most likely to have high-grade cervical intraepithelial neoplasia (CIN). A total of 266 women with mildly abnormal Papanicolaou (Pap) smear results (160 with ASCUS and 106 with LSIL) concurrently underwent Hybrid Capture II testing, repeat Pap smear, and colposcopy-directed biopsies. Overall, the underlying prevalence of histologically confirmed CIN2/3 was 16.9% (27/160) in women with ASCUS and 29.2% (31/106) in those with LSIL. High-risk HPV DNA was detected in 55% and 88.7%, respectively. The sensitivity of CIN2/3 detection by HPV DNA was 96.3% (26/27) and 100% (31/31) among women with ASCUS and LSIL, respectively. A positive baseline HPV test in women with ASCUS or LSIL is clinically equivalent, requiring colposcopic examination and denoting an approximately one-third chance of having CIN2/3. Among women with ASCUS, a negative HPV test strongly indicates that the patient is free of CIN2/3, which should minimize a patient's anxiety and unnecessary colposcopic examinations.

Quantifying the Risk of Cervical Intraepithelial Neoplasia in Women with Unsatisfactory Colposcopy Results

To define the risk of high-grade cervical intraepithelial neoplasia (CIN 2,3) among women with unsatisfactory colposcopy results who underwent a loop electrosurgical excision procedure. Loop electrosurgical excision procedures were performed for clinical indications by residents supervised by attending obstetrician-gynecologists at an urban public hospital referral clinic. Specimens obtained between July 1, 1996, and April 30, 2002, were retrieved retrospectively after grading and recording in an institutional database. The endpoint of interest was high-grade cervical disease, a composite of CIN 2, CIN 3, and cancer, in excision specimens. Of 169 evaluable patients, five (3%) had cancer. High-grade disease was found in 6 of 21 patients (29%) without a colposcopic lesion, in 13 of 33 patients (36%) with only koilocytosis on colposcopic biopsy, in 15 of 55 patients (27%) with CIN 1, in 13 of 25 patients (54%) with CIN 2, and in 26 of 35 patients (74%) with CIN 3 (p < 0.001). High-grade disease was associated with the grade of referral cytologic results, cytologic analysis repeated at colposcopy, and colposcopic biopsy (p < 0.001 for all). Limiting excision to women with cytologic results at the time of colposcopy read as atypical squamous cells of undetermined significance or worse yielded a high-grade disease prevalence of 12%, with a sensitivity of 92%, specificity 46%, negative predictive value 88%, and positive predictive value 56%. Referral cytologic results, colposcopic biopsy, age, and endocervical curettage results did not seem to identify women at low risk for high-grade disease. Women with negative cytologic results at the time of colposcopy have a low risk for high-grade disease and may avoid a loop electrosurgical excision procedure despite unsatisfactory colposcopy.

Natural History of Grade 1 Cervical Intraepithelial Neoplasia in Women With Human Immunodeficiency Virus

We sought to estimate rates of progression and regression of grade 1 cervical intraepithelial neoplasia (CIN 1) among women with human immunodeficiency virus (HIV). In a multicenter prospective cohort study, HIV-seropositive and HIV-seronegative women were evaluated colposcopically after receiving an abnormal cytology test result between November 1994 and September 2002. Women with CIN 1 were included, except those who had undergone hysterectomy, cervical therapy, or had CIN 2-3 or cervical cancer. Those women who were included were followed cytologically twice yearly, with colposcopy repeated for atypia or worse. We followed 223 women with CIN 1 (202 HIV seropositive and 21 HIV seronegative) for a mean of 3.3 person-years. Progression occurred in 8 HIV-seropositive women (incidence density, 1.2/100 person-years; 95% confidence interval [CI] 0.5-2.4/100 person-years) and in no HIV seronegative women. Regression occurred in 66 (33%) HIV-seropositive women (13/100 person-years, 95% CI 10-16/100 person-years) versus 14 (67%) seronegative women (32/100 person-years, relative risk 0.40, 95% CI 0.25-0.66; P < .001). In multivariate analysis, regression was associated with human papillomavirus (HPV) detection (hazard ratio [HR] for low risk 0.28, 95% CI 0.13-0.61, P = .001; and for high-risk 0.34, 95% CI 0.20-0.55, P < .001 versus no HPV detected) and Hispanic ethnicity (HR 0.48, 95% CI 0.230.98; P = .04); HIV serostatus was only marginally linked to regression (HR 0.52, 95% CI 0.27-1.03; P = .06), but seropositive women were less likely to regress when analysis was limited to 146 women with HPV detected at CIN 1 diagnosis (HR 0.18, 95% CI 0.05-0.62; P = .006). Grade 1 cervical intraepithelial neoplasia infrequently progresses in women with HIV. Thus, observation appears safe absent other indications for treatment. II-1.

Treatment for cervical intraepithelial neoplasia and risk of preterm delivery.

It is unclear whether treatments for cervical intraepithelial neoplasia (CIN) increase the subsequent risk of preterm delivery. Most studies have lacked sufficient sample size, mixed heterogeneous subtypes of preterm delivery, and failed to control for confounding factors. To determine whether cervical laser and loop electrosurgical excision procedure (LEEP) treatments increase risk of preterm delivery and its subtypes. Retrospective cohort study conducted among women evaluated at a colposcopy clinic serving Auckland, New Zealand (1988-2000), comparing delivery outcomes of untreated women (n = 426) and those treated (n = 652) with laser conization, laser ablation, or LEEP. Record linkage using unique health identifiers identified women who had subsequent deliveries. Total preterm delivery and its subtypes, spontaneous labor and premature rupture of membranes before 37 weeks' gestation (pPROM). The overall rate of preterm delivery was 13.8%. The rate of pPROM was 6.2% and the rate of spontaneous preterm delivery was 3.8%. Analyses showed no significant increase in risk of total preterm delivery (adjusted relative risk [aRR], 1.1; 95% confidence interval [CI], 0.8-1.5) or spontaneous preterm delivery (aRR, 1.3; 95% CI, 0.7-2.6) for any treatment. Risk of pPROM was significantly increased following treatment with laser conization (aRR, 2.7; 95% CI, 1.3-5.6) or LEEP (aRR, 1.9; 95% CI, 1.0-3.8), but not laser ablation (aRR, 1.1; 95% CI, 0.5-2.4). Moreover, risk of pPROM and total preterm delivery increased significantly with increasing height of tissue removed from the cervix in conization. Women in the highest tertile of cone height (> or =1.7 cm) had a greater than 3-fold increase in risk of pPROM compared with untreated women (aRR, 3.6; 95% CI, 1.8-7.5). LEEP and laser cone treatments were associated with significantly increased risk of pPROM. Careful consideration should be given to treatment of CIN in women of reproductive age, especially when treatment might reasonably be delayed or targeted to high-risk cases.

Evaluación diagnóstica de la citología, la colposcopia y la biopsia en mujeres con sospecha de lesiones precursoras de neoplasia cervical intraepitelial

ObjectivesTo evaluate the validity of cytology, colposcopy and colposcopically directed biopsy compared with histology of the surgical specimen in the diagnosis of cervical intraepithelial neoplasia in women with one or more positive diagnostic tests and to evaluate the diagnostic yield of biopsy throughout the range of cutoff points. Pacientes and métodosWe performed a cross-sectional, retrospective study. The study population consisted of women who underwent surgical excision due to repeatedly abnormal cytology, microscopically abnormal colposcopy and/or biopsy with some alterations. For each test the sensitivity, specificity, positive predictive value, negative predictive value and probability ratios with their 95% confidence intervals were calculated. The Receiver Operating Characteristics (ROC) curve was calculated for biopsy. ResultsColposcopy showed he greatest sensitivity (95%) but its specificity was 27.3%. Biopsy showed the highest predictive values and probability ratio. The combination of the two tests improved the predictive values: with the prevalence found in the study, positive results of both cytology and biopsy showed a positive predictive value of 97%. The most appropriate biopsy cutoff point for decisionmaking was moderate dysplasia. ConclusionsThe combination of cytology, colposcopy and biopsy in selected patients increases the diagnostic validity of precursor lesions of the uterine cervix. The most appropriate biopsy cut-off point for decisionmaking is moderate dysplasia.

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.

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. 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. Cross-sectional. Colposcopy Clinic in a University hospital. 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. 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. 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.