Confirmed Cervical Intraepithelial Neoplasia Research Articles

Cigarette smoking, oncogenic human papillomavirus, Ki-67 antigen, and cervical intraepithelial neoplasia.

Although cigarette smoking has been identified as a cofactor for cervical neoplasia, it is not clear whether smoking exerts an early or late effect on the evolution of human papillomavirus (HPV)-related lesions. A case-control study of Washington State women who presented for routine gynecologic care from 1997 to 2001 was conducted. All women underwent cytologic testing and HPV DNA screening. Those with abnormal cytology findings or a positive oncogenic HPV test and a random sample of women negative on both tests were referred for colposcopically directed cervical biopsy with repeated testing. Among 461 women with oncogenic HPV were 181 controls with negative histology, 137 cases with histologically confirmed cervical intraepithelial neoplasia (CIN) grade 1 (CIN1), and 143 cases with histologically confirmed CIN grades 2-3 or higher (>/= CIN2-3). Smoking information was obtained by questionnaire. Immunohistochemistry testing for Ki-67 was performed on a subset of biopsy specimens (n = 139). Smoking 10 or more cigarettes per day was associated with >/= CIN2-3 (adjusted odds ratio = 2.6, 95% confidence interval: 1.3, 5.5) and CIN1 (adjusted odds ratio = 2.5, 95% confidence interval: 1.2, 5.3). Heavy smoking was positively associated with Ki-67 but not with repeated detection of oncogenic HPV. Since smoking was associated with both CIN1 and >/= CIN2-3, cigarette by-products may affect the early evolution of HPV-related lesions, possibly by increasing the rate of cell turnover.

2001 Consensus Guidelines for the Management of Women with Cervical Intraepithelial Neoplasia

To provide consensus guidelines for the management of women with histologically confirmed cervical intraepithelial neoplasia (CIN), which can act as a precursor to invasive cervical cancer and represents one of the most common significant gynecologic diseases of women of reproductive age. An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others invited by the American Society for Colposcopy and Cervical Pathology (ASCCP). Guidelines for the management of women with CIN were developed through a multistep process. Working groups, who performed formal literature reviews and obtained input from the professional community at large by way of an interactive Internet-based bulletin board, developed draft management guidelines. At the ASCCP Consensus Conference, September 6-8, 2001, in Bethesda, Maryland, all guidelines were discussed, revised, and adopted by formal vote. Evidence-based guidelines have been developed for the management of women with biopsy-confirmed CIN.

2001 Consensus Guidelines for the management of women with cervical intraepithelial neoplasia

Objective: The study was undertaken to provide consensus guidelines for the management of women with histologically confirmed cervical intraepithelial neoplasia (CIN) that can act as a precursor to invasive cervical cancer and represents one of the most common significant gynecologic diseases of women of reproductive age. Participants: An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others were invited by the American Society for Colposcopy and Cervical Pathology (ASCCP). Consensus Process: Guidelines for the management of women with CIN were developed through a multistep process. Draft management guidelines were developed by working groups who performed formal literature reviews and obtained input from the professional community at large by way of an interactive internet-based bulletin board. At the ASCCP Consensus Conference, September 6 through 8, 2001, in Bethesda, Md, all guidelines were discussed, revised, and adopted by formal vote. Conclusion: Evidence-based guidelines have been developed for the management of women with biopsy-confirmed CIN. (Am J Obstet Gynecol 2003;189:295-304.)

Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirus testing.

Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57–132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93–88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72–82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening. © 2000 Cancer Research Campaign http://www.bjcancer.com

A prospective study of biopsy-confirmed cervical intraepithelial neoplasia grade 1: colposcopic, cytological, and virological risk factors for progression.

The objective of this prospective study of histologically confirmed cervical intraepithelial neoplasia (CIN) (including equivocal CIN1) was to determine risk factors for progression to histologically confirmed CIN3, particularly human papillomavirus (HPV) types and cofactors. We postulated that HPV DNA positivity would be a strong, prospective risk factor for progression. Possible participants were referred with an abnormal cytological diagnosis of CIN1 or lower-grade disease or external genital warts. Women with histologically confirmed CIN1 (including koilocytotic atypia) or equivocal CIN1 were eligible for follow-up. Of these, 163 women were assessed every 3 months (if a lesion were present) or every 6 months (if a lesion regressed colposcopically during the course of the study), for up to 52 months. Progression was defined histologically, whereas persistence and regression were defined by combined cytological, colposcopic, and histological assessments. Subjects who progressed to a biopsy-confirmed CIN3 or who developed a lesion that was clinically unsafe to follow up (i.e., because of movement into the endocervical canal), were removed from the study and were treated. A total of 237 patients were evaluated as possible participants. The 74 exclusions at enrollment included 33 patients who had an entry diagnosis of CIN2 to CIN3 or who had lesions that were otherwise already unsafe to follow up, 39 who did not have a lesion on colposcopically directed biopsy, and 2 who were immediately noncompliant. Among the remaining 163 participants, the overall progression rate to histologically confirmed CIN3 was 8%, the persistence rate was 49%, and the regression rate was 43%. All progressions occurred among women who were HPV DNA-positive and had colposcopically immature abnormal transformation zones.

Evaluation of the ThinPrep Pap Test in Clinical Practice

To compare the cytologic diagnoses and specimen adequacy of the ThinPrep Pap Test with historical data within a distinct patient population to assess test performance and its impact on clinical practice. A total of 16,314 ThinPrep Pap tests were processed and evaluated at Fletcher Allen Health Care over a seven-month period. A subset of 8,574 tests from a selected provider group (cohort) was compared to the historical conventional cervical cytologic smear data from the cohort population for both cytologic diagnoses and specimen adequacy. The cohort consisted of 12 practice groups, including 60 physicians and providers, utilizing the ThinPrep Pap Test as their primary cervical cancer screening sampling technique. Cytologic diagnoses and specimen adequacy were classified using the Bethesda system. Using a three-tiered diagnostic system similar to the Cytyc clinical trials (within normal limits [WNL], atypical squamous cells of undetermined significance [ASCUS]/atypical glandular cells of undetermined significance [AGUS] and low grade squamous intraepithelial lesion and higher [LSIL]+), the ThinPrep method increased the percentage of cases that could be definitively diagnosed as WNL by 1.71%, lowered the percentage of ambiguous or borderline cases diagnosed as ASCUS/AGUS by 26.59% and increased the percentage of cases diagnostic of LSIL+ by 52.15% in the cohort population. Further subdivision by the Bethesda classification showed that the identification of infectious agents increased 25.51% and the detection of high grade squamous intraepithelial lesion/carcinoma increased 55.14%. Concurrently, cases reported as benign cellular changes (reactive/reparative) decreased 23.1%, and the percentage of cases reported as unsatisfactory/"limited by ..." was reduced 52.71%. Histologic correlation of cases reported as squamous intraepithelial lesion revealed that the percentage of patients with subsequent benign biopsies was reduced by 31.7% utilizing the ThinPrep technique. Further, the percentage of ThinPrep patients with histologically confirmed cervical intraepithelial neoplasia (CIN) 1 and CIN 2/3 increased by 16.3% and 9.3%, respectively. Implementation of the ThinPrep Pap Test resulted in statistically significant improvements in both diagnostic yield and specimen adequacy, as seen by others in clinical trials. Comparison of results to historical data within a cohort population reinforced earlier data and lent further support to the claim that the ThinPrep Pap Test is "significantly more effective" than the conventional smear in clinical practice.

Review of outcomes of atypical squamous cells of undetermined significance papanicolaou smears for 1991 and 1992, with follow-up through 1995.

Our aim was to review 1,754 consecutive Papanicolaou (Pap) smears from 1991 to 1992 to evaluate initial findings and disease progression through December of 1995. The study used analysis of data in the Gundersen Lutheran Medical Center Colposcopy Clinic's computerized registry. A total of 1,754 patients were followed, and findings were analyzed for progression and age-related outcomes. At initial evaluation by a trained ACOG member colposcopist, 11% of patients with atypical squamous cells of undetermined significance (ASCUS) Pap smears had histologically confirmed cervical intraepithelial neoplasia (CIN) I lesion and 7% a CIN II or III lesion. After a negative initial evaluation for an ASCUS Pap smear, an additional 8.4% smears went on to to demonstrate histologically confirmed CIN II or III, and an additional 4.7% revealed a CIN I. An ASCUS Pap smear requires evaluation by a care provider trained in colposcopy and management of abnormal Pap smears.

Effects of β-Carotene and Other Factors on Outcome of Cervical Dysplasia and Human Papillomavirus Infection

Women with histopathologically confirmed cervical intraepithelial neoplasia (CIN) were followed at 3-month intervals in a randomized double-blinded trial to evaluate the efficacy of β-carotene to cause regression of CIN. Questionnaire data, plasma levels of micronutrients, and a cervicovaginal lavage for human papillomavirus (HPV) detection were obtained at each visit, and an endpoint biopsy was performed at 9 months. Sixty-nine subjects had a biopsy endpoint evaluation; 9 of 39 (23%) subjects in the β-carotene group versus 14 of 30 (47%) in the placebo group had regression of CIN (P= 0.039). Independent risk factors for persistent CIN at 9 months included type-specific persistent HPV infection (OR = 11.38,P= 0.006) and continual HPV infection with a high viral load (OR = 14.25,P= 0.007) at baseline and 9 months, an initial diagnosis of ≥CIN II (OR = 6.74,P= 0.016), and older age (OR for ≥25 years = 4.10,P= 0.072). After controlling for these factors, the β-carotene and placebo groups did not differ in risk for having CIN at 9 months (OR = 1.53,P= 0.550). Resolution of baseline HPV infection was significantly correlated with non-high-risk HPV types (RR = 2.94,P= 0.015), age <25 years (RR = 2.62,P= 0.014), and douching after sexual intercourse (RR = 3.02,P= 0.012), but not with randomization group. Our data indicate that a large proportion of mild CIN lesions regress; age and HPV infection play an important role in the natural course of CIN; and repeated HPV testing may have a value in distinguishing women who need aggressive treatment for CIN versus those who do not. Supplementation of β-carotene does not appear to have a detectable benefit in treatment of CIN.

An evaluation of human papillomavirus testing as part of referral to colposcopy clinics

To determine the usefulness of human papillomavirus (HPV) testing as a triage method for predicting which women referred to a colposcopy clinic were most likely to have histologically confirmed cervical intraepithelial neoplasia (CIN).Papanicolaou tests, ViraPap tests for HPV infection, and colposcopically directed biopsies were performed concurrently on 482 women referred to a student health colposcopy clinic.The results demonstrated that HPV positivity was associated with a greatly increased likelihood of histologic confirmation of CIN, especially among women with concurrent cytologic findings that were negative or showed only atypical squamous cells of undetermined significance.Testing for HPV appears to have a role in the triage of students now being referred to our colposcopy clinic. A combination of HPV testing and repeated cytologic screening would provide reasonably sensitive screening for cervical neoplasia while limiting the use of colposcopic services, which are currently overburdened. The eventual usefulness of HPV testing will depend on the cost and availability of colposcopy services, the cost of Papanicolaou tests, the cost and accuracy of HPV tests, and the predictive value of HPV detection in the population being screened.

Laser excision of the transformation zone as treatment of cervical intraepithelial neoplasia with satisfactory colposcopy

A series of 123 patients with histologically confirmed cervical intraepithelial neoplasia (CIN) with satisfactory colposcopy were treated with outpatient laser excision of the transformation zone. Punch biopsy and/or endocervical curettage proved CIN III in 111 patients (90%). Histology of the laser excision specimen showed microinvasive disease in 3 patients. Operative hemorrhage occurred in 2 patients. The follow-up ranged from 12 to 59 months (median, 30 months). Four patients were found to have residual/recurrent CIN during the observation period, resulting in a cure rate of 97%. All patients with recurrence are free of disease after a second laser treatment. Only 1 patient out of 26 with involved resection margins relapsed. Laser excision of the transformation zone is proposed as a suitable replacement for laser vaporization in patients with CIN with satisfactory colposcopy, offering the major advantage of providing a histological specimen without an increase in morbidity.

Laser excision of the transformation zone as treatment of cervical intraepithelial neoplasia with satisfactory colposcopy

A series of 123 patients with histologically confirmed cervical intraepithelial neoplasia (CIN) with satisfactory colposcopy were treated with outpatient laser excision of the transformation zone. Punch biopsy and/or endocervical curettage proved CIN III in 111 patients (90%). Histology of the laser excision specimen showed microinvasive disease in 3 patients. Operative hemorrhage occurred in 2 patients. The follow-up ranged from 12 to 59 months (median, 30 months). Four patients were found to have residual/recurrent CIN during the observation period, resulting in a cure rate of 97%. All patients with recurrence are free of disease after a second laser treatment. Only 1 patient out of 26 with involved resection margins relapsed. Laser excision of the transformation zone is proposed as a suitable replacement for laser vaporization in patients with CIN with satisfactory colposcopy, offering the major advantage of providing a histological specimen without an increase in morbidity.

Analysis of transforming gene regions of human papillomavirus type 16 in normal cervical smears.

Exfoliated cells from the uterine cervix of 102 Hungarian women with no cytological abnormality were screened using the polymerase chain reaction (PCR) for human papillomavirus (HPV) type 16 infection. Twenty-nine patients with histologically confirmed cervical intraepithelial neoplasia (CIN) served as reference cases. PCR was performed with 2 different HPV 16 specific oligonucleotide primer pairs flanking a 300 and a 200 base-pair fragment from the early 6 (E6) and early 7 (E7) genes, position 215-514 and 605-805. The specimens exhibited the same proportions of type 16 sequences specific for the tested regions. 8.8% (9/102) of normal samples showed amplification for HPV type 16 E6 and E7 regions, while 48.3% (14/29) of CIN biopsies were positive for the same gene sequences.

Quantitative determination of acid-labile dna in cervical intraepithelial neoplasia

Using a modified Feulgen hydrolysis procedure and integrating microdensitometry, the acid-labile nuclear DNA in exfoliated cervical epithelial cells was quantified in a range of histologically confirmed cervical intraepithelial neoplasia (CIN), invasive cancer, and normal controls. The mean relative optical densities obtained for each sample group showed an increase from normal epithelium, through CIN grades, to invasive cancer. Although there was some overlap between groups, the difference in the overall mean values between the adjacent groups was statistically significant. The sensitivity of the test was 87.1% with a specificity of 99.2% and a predictive value of 99.5%, with no false negatives in the severe dysplasia and cancer groups. Quantitative data allows the threshold value to be altered to vary the sensitivity and specificity according to prevailing requirements. This suggests the possibility of using quantitative acid-labile DNA measurements to improve existing screening for cervical precancer.

Large loop excision of the transformation zone (LLETZ) compared to carbon dioxide laser in the treatment of CIN: a superior mode of treatment

A series of 199 patients with histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or III were allocated by hospital number to receive out-patient treatment by carbon dioxide laser vaporization or large loop excision of the transformation zone (LLETZ). All patients received local anaesthesia. The women in the LLETZ group experienced less post operative haemorrhage, less discomfort, operative time was greatly reduced, and histological material was available for confirmation of the diagnosis. There was no significant difference in recurrence of CIN after treatment between the two groups. At 6 month follow-up, recurrence rates of 8.2% (CIN II) and 7.5% (CIN III) were observed in the laser-group and 5% (CIN II) and 5.3% (CIN III) in the LLETZ group. Further advantages of LLETZ are reduced capital expenditure and no hazard to the eyesight of the surgeon, but laser treatment is preferable in patients with widespread vaginal involvement.

The significance of human papilloma virus atypia ('wart virus infection') found alone on cervical cytology screening.

A series of 429 patients has been analysed in which the cytology smear report suggested human papillomavirus (HPV) infection alone. All patients were examined colposcopically and in 58 (13.6%) associated histologically confirmed cervical intraepithelial neoplasia (CIN) was demonstrated. CIN subsequently developed in an additional 10% of those patients who returned for follow-up over an ensuing 3-year period. Follow-up with repeat cervical cytology smears alone was unreliable as 4% of patients even with normal repeat smears has histologically proven CIN and a further 4% of these patients subsequently developed CIN. Colposcopy is recommended in all patients whose cytology smear shows HPV infection.

Screening for cervical intraepithelial neoplasia and cancer in the Sheffield STD clinic.

I undertook a prospective study of the incidence of histologically confirmed cervical intraepithelial neoplasia (CIN) and cancer in women attending a sexually transmitted disease (STD) clinic, and correlated the findings to cervical cytology reports, age, and history of STD of the affected women. Of 2017 women screened, 75 (3.7%) had dyskaryotic cervical smears. Colposcopically directed biopsy tests gave an overall detection rate of 0.55% for CIN3, which was similar to the national average. The false negative rate was 2.9% and cytology tests alone underestimated the degree of pathological change in 12 (30%) of 40 women with mild dyskaryosis. Women under 20 years old made up 43% of those with CIN1 and 38% of those with CIN2. The detection rate of CIN3 was 0.65% for women aged 15-34, which was higher than the national average and suggested earlier onset of CIN3 in our clinic population. There was a high association between genital warts and cervical precancer. This preliminary study confirms the need for routine non-selective screening of women attending STD clinics by cervical cytology tests, colposcopic examination, and biopsy tests where indicated.