Atypical Cells Of Undetermined Significance Research Articles

An 80-Year-Old Woman With Vaginal Prolapse

DR SHIP: Mrs H is an 80-year-old woman with Medicare insurance who recently began feeling tissue coming out of her vagina. She called to make an appointment to see her longtime gynecologist. She feels generally well and lives with her husband of more than 50 years. She has systolic hypertension and osteoporosis. Decades ago, Mrs H had 4 vaginal deliveries of healthy, term infants. She has had regular Papanicolaou smear screening, but her most recent smear showed atypical cells of undetermined significance. It was her first abnormal smear. She denies vaginal bleeding or urinary incontinence; she does experience some urinary urgency. Her bowels are regular. She is sexually active, without dyspareunia or other problems. Her medications include enalapril, hydrochlorothiazide, and alendronate. A daughter and sister have been diagnosed with breast cancer. She has good exercise tolerance, is very active, and wants to preserve her quality of life. On physical examination, the patient is a thin woman in no distress. Her weight is 125 lb, and her height is 63 inches. The blood pressure is 170/70 mm Hg, heart rate 60/min and regular. On pelvic examination, her cervix has prolapsed 2 cm past the hymen; there is very little cystocele or rectocele. Aside from the abnormal cervical smear, her laboratory values are unremarkable. Mrs H is not eager to try a pessary. She is trying to decide whether to have surgery or to do nothing about her prolapse at this point in time.

Predicting CIN2+ when detecting HPV mRNA and DNA by PreTect HPV‐proofer and consensus PCR: A 2‐year follow‐up of women with ASCUS or LSIL pap smear

It has been suggested that human papillomavirus (HPV) testing improves follow-up of atypical cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) in cervical cancer screening programs. To evaluate the prognostic value of including HPV testing as an adjunct to cytology, we carried out a 2-year follow-up study of 77 women with ASCUS or LSIL Papanicolaou (Pap) smear in the Norwegian Cervical Cancer Screening Program (NCCSP) for detection of histological cervical intraepithelial neoplasia (CIN) 2+. The study includes a comparison between viral mRNA and DNA detection. PreTect HPV-Proofer was used for HPV E6/E7 mRNA detection from the 5 high-risk types 16, 18, 31, 33 and 45, and Gp5+/6+ consensus PCR was used for HPV DNA detection. Twice as many women were positive for HPV DNA (54.6%) than for HPV mRNA (23.4%). PreTect HPV-Proofer and consensus PCR had a sensitivity of 85.7% (95% confidence interval [CI] = 42.1-99.6) for detecting CIN2+ during follow-up. The specificity was significantly higher for PreTect HPV-Proofer, 84.9% (95% CI = 73.9-92.5), than for consensus PCR, 50.0% (95% CI = 37.4-62.6). PreTect HPV-Proofer positive women were 69.8 times (95% CI = 4.3-1137.3) more likely to be diagnosed with CIN2+ within 2 years than PreTect HPV-Proofer negative women. Consensus PCR-positive women were 5.7 times (95% CI = 0.6-52.0) more likely to be diagnosed with CIN2+ within 2 years than PCR-negative women. With equal sensitivity and higher specificity than consensus PCR, the PreTect HPV-Proofer might offer an improvement for the triage of women with ASCUS or LSIL Pap smear.

Combining Human Papillomavirus Testing or Cervicography With Cytology to Detect Cervical Neoplasia

Cervicography and oncogenic human papillomavirus (HPV) testing have been proposed for improving the accuracy of cervical cancer screening. To examine whether cervicography and HPV testing can improve beyond chance the detection of cervical intraepithelial neoplasia (CIN) 2 or 3 in women with atypical cells of undetermined significance or low-grade squamous intraepithelial lesions on cytology. Cross-sectional analysis. Oncogenic HPV testing by Hybrid Capture II assay or cervicography combined with cytology was compared with the reference standard of colposcopy with directed biopsy. Community family practices. Three hundred four women with low-grade cytologic abnormality. The gain in accuracy for detecting histologic CIN 2 or 3 or carcinoma. Because an adjunct test may improve sensitivity by chance alone, the sensitivity or specificity if the second test performed randomly was estimated. Cervical intraepithelial neoplasia 2 or 3 was found in 11.8% (36/304) of the women and invasive squamous cell carcinoma in 0.3% (1/304). The sensitivity of cytology for detecting CIN 2 or 3 was 73.0% and increased by 21.6% to 94.6% with the addition of a cervigram showing a low-grade lesion or higher or a positive HPV test result. These gains were reduced to 8.1% and 10.8% above the sensitivities expected if the additional tests performed randomly. The corresponding specificities decreased from 49.1% to 32.2% and 33.0%. There was insufficient power to determine whether observed sensitivities were statistically significantly higher than the expected sensitivities. Adjunctive HPV testing or cervicography may provide similar gains in sensitivity, but they can appear misleadingly large if chance increases are not taken into account.

Combining Human Papillomavirus Testing or Cervicography With Cytology to Detect Cervical Neoplasia

Abstract Context.—Cervicography and oncogenic human papillomavirus (HPV) testing have been proposed for improving the accuracy of cervical cancer screening. Objective.—To examine whether cervicography and HPV testing can improve beyond chance the detection of cervical intraepithelial neoplasia (CIN) 2 or 3 in women with atypical cells of undetermined significance or low-grade squamous intraepithelial lesions on cytology. Design.—Cross-sectional analysis. Oncogenic HPV testing by Hybrid Capture II assay or cervicography combined with cytology was compared with the reference standard of colposcopy with directed biopsy. Setting.—Community family practices. Participants.—Three hundred four women with low-grade cytologic abnormality. Main Outcome Measures.—The gain in accuracy for detecting histologic CIN 2 or 3 or carcinoma. Because an adjunct test may improve sensitivity by chance alone, the sensitivity or specificity if the second test performed randomly was estimated. Results.—Cervical intraepithelial neop...

Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia.

The appropriate management of women with minor cytologic lesions in their cervix is unclear. We performed a meta-analysis to assess the accuracy of human papillomavirus (HPV) DNA testing as an alternative to repeat cytology in women who had equivocal results on a previous Pap smear. Data were extracted from articles published between 1992 and 2002 that contained results of virologic and cytologic testing followed by colposcopically directed biopsy in women with an index smear showing atypical cells of undetermined significance (ASCUS). Fifteen studies were identified in which HPV triage and the histologic outcome (presence or absence of a cervical intraepithelial neoplasia of grade II or worse [CIN2+]) was documented. Nine, seven, and two studies also documented the accuracy of repeat cytology when the cutoff for abnormal cytology was set at a threshold of ASCUS or worse, low-grade squamous intraepithelial lesion (LSIL) or worse, or high-grade squamous intraepithelial lesion (HSIL) or worse, respectively. Random-effects models were used for pooling of accuracy parameters in case of interstudy heterogeneity. Differences in accuracy were assessed by pooling the ratio of the sensitivity (or specificity) of HPV testing to that of repeat cytology. The sensitivity and specificity were 84.4% (95% confidence interval [CI] = 77.6% to 91.1%) and 72.9% (95% CI = 62.5% to 83.3%), respectively, for HPV testing overall and 94.8% (95% CI = 92.7% to 96.9%) and 67.3% (95% CI = 58.2% to 76.4%), respectively, for HPV testing in the eight studies that used the Hybrid Capture II assay. Sensitivity and specificity of repeat cytology at a threshold for abnormal cytology of ASCUS or worse was 81.8% (95% CI = 73.5% to 84.3%) and 57.6% (95% CI = 49.5% to 65.7%), respectively. Repeat cytology that used higher cytologic thresholds yielded substantially lower sensitivity but higher specificity than triage with the Hybrid Capture II assay. The ratio of the sensitivity of the Hybrid Capture II assay to that of repeat cytology at a threshold of ASCUS or worse pooled from the four studies that used both triage tests was 1.16 (95% CI = 1.04 to 1.29). The specificity ratio was not statistically different from unity. The published literature indicates that the Hybrid Capture II assay has improved accuracy (higher sensitivity, similar specificity) than the repeat Pap smear using the threshold of ASCUS for an outcome of CIN2+ among women with equivocal cytologic results. The sensitivity of triage at higher cytologic cutoffs is poor.

Are Muslim women less susceptible to oncogenic human papillomavirus infection? A study from rural eastern India

Muslim women are known to have lower incidences of cervical cancer and/or human papillomavirus (HPV) infection. Here we aim to determine any association that may be present between the oncogenic HPV16/18 infections and abnormal cytological lesions along with demographic and other attributes among Indian Muslim women (n= 478) and compare with the neighboring Hindus (n= 534) from a prospective cohort study. Agewise distribution of both subject-groups is similar. HPV16/18 infection is present in 9.6% Muslims and 7.5% Hindu women. Jointly atypical cells of undetermined significance (a typical cells of undetermined significance) and HPV16/18 are present in seven Muslim and two Hindu women. No high squamous intraepithelial lesions or cervical cancer is detected at the baseline. HPV16/18 infections show trends that varied with age, a nonlinear trend among Muslim women. In Hindu women the prevalence is highest at age ≤24 years, which linearly drops with increasing age. Abnormal cytology increases significantly in both religion-groups with increasing age. The data show that these Indian Muslim women are equally susceptible to HPV16/18 infection and for the development of abnormal cytology. There is a paucity in epidemiological data, which justifies the need to screen women of all religions for cervical cancer (that includes oncogenic HPV testing).

Use of a Liquid-Based, Thin-Layer Pap Test in a Community Hospital

To evaluate the direct-to-vial efficacy of the SurePath Pap test (TriPath Imaging, Burlington, North Carolina, U.S.A.) in a community hospital laboratory and to assess its impact on productivity, as measured by Pap test turnaround times (TATs). A total of 8,771 SurePath Pap tests were compared to 5,055 conventional Pap smears collected and processed over the same 12-month period. SurePath histologic correlation rates were compared to historical correlation rates for conventional Pap smears. Pap test TATs for 3 months prior to implementing SurePath were compared to TATs for the last 3 months of the study, which included an approximate 70:30 ratio of SurePath to conventional Pap tests. Laboratory staffing was unchanged, and mean monthly accessions were relatively constant. SurePath showed statistically significant improvements in the detection of low grade (LSIL) (196%) and high grade (HSIL) (243%) squamous intraepithelial lesions (SILs) relative to conventional Pap smears. The atypical cells of undetermined significance (ASCUS) rate remained nearly constant with SurePath, while the ASCUS/SIL ratio decreased by 68%. Unsatisfactory rates declined 81%. Histologic correlation rates with SurePath increased over those of conventional Pap smears. Pap test mean TATs improved 73% with SurePath. Sure-Path detected significantly more cases of LSIL and HSIL than conventional smears without compromising specificity. The ASCUS/SIL ratio and unsatisfactory rate declined dramatically. Pap test TATs also improved markedly with SurePath.

Prospective Evaluation of Colposcopic Features in Predicting Cervical Intraepithelial Neoplasia: Degree of Acetowhite Change Most Important

The results of three coordinated studies using patients from community family practices and a university student health clinic in Ontario, Canada, between May 1995, and October 1998 were presented in this paper. Two randomized trials involved human papillomavirus (HPV) testing in women at least 17 years of age who were undergoing routine cytologic screening after an abnormal Pap smear. The third study was a cross-sectional trial of HPV testing in women 18 years of age and older with ASCUS (abnormal squamous cells of undetermined significance) who had been referred for colposcopic examination. The data presented are the results of colposcopic examination and directed biopsy in these patients. At colposcopy, 5% acetic acid was applied to the cervix, and the features of the abnormal transformation zone were evaluated. The colposcopist used a 3-point scale to rate the degree of acetowhite change, the size of the lesion margin, and the blood vessel pattern in the lesion (Table 1). The site with the greatest point total for all 3 features was biopsied. A total of 301 patients had data available for evaluation. The women were an average of 40 years of age, and most (80%) were high school graduates, Forty-nine percent were in a committed relationship, 45% were smokers, and 43% were taking oral contraceptives. They had an average of 4 lifetime sexual partners and an average age at first intercourse of 17.3 years. Cervical cytology diagnosed atypical cells of undetermined significance (ASCUS) or a low-grade intraepithelial lesion (LSIL) in 81% of patients. Nineteen percent had a high-grade intraepithelial lesion (HSIL). Histologic examination of the biopsy specimen showed cervical intraepithelial neoplasia (CIN) 1 in 43 patients (14%) and CIN 2 or 3 in 96 (32%). Biopsy results were normal for 43% percent of patients (n = 162). In univariate logistic regression analysis, there was a significant association with the presence of CIN of any type for each of the 3 cervical features evaluated. A score of 2 points on the 3-point scale had an odds ratio for association with any CIN of 2.7 for lesion margin size, 10.1 for acetowhite change, and 2.0 for blood vessel pattern. However, when unconditional and stepwise multivariate regression analyzes were performed, the results of each analysis showed that only the degree of acetowhite change retained a significant association with CIN 2 or 3. A score of 2 had an odds ratio for association with CIN 2 or 3 of 2.4 for lesion margin size and 2.11 for blood vessel pattern compared with 22.1 for acetowhite change.

Long-Term Administration of Intravaginal Dehydroepiandrosterone on Regression of Low-Grade Cervical Dysplasia – A Pilot Study

Although many dysplastic cervical lesions regress spontaneously, treatment is common due to concern for progression. Lesions persist or progress in women whose immune systems are unable to clear infection by human papillomavirus (HPV). Dehydroepiandrosterone (DHEA) is an adrenal steroid that has both immune modulatory and tumor inhibitory activity. A pilot study was conducted to examine the feasibility, safety and potential efficacy of intravaginal DHEA in women with low-grade cervical dysplasia. Twelve women with low-grade dysplasia, confirmed by colposcopic exam, were given 150 mg of intravaginal micronized DHEA daily for up to 6 months. Follow-up evaluations of the cervix were done at 3 and 6 months of use. DHEA, DHEA-S, androstenedione and testosterone levels were also measured. By the end of the study period, 10 of the 12 women (83%) had no evidence of dysplasia; the remaining 2 had normal colposcopic exams but cytology showing atypical cells of undetermined significance. There were no serious side effects. Androstenedione levels were elevated at 3 months, whereas testosterone levels were unchanged over the course of treatment. The results suggest that intravaginal DHEA is safe and well tolerated and may promote regression of low-grade cervical lesions. Further study is needed to establish efficacy.

Aktuelle Wertigkeit der HPV-Testung in der klinischen Praxis

Human papillomavirus (HPV) infection is the most important singular factor in the etiology of cervical cancer. Among young women, infection with HPV is a common and transient occurrence with prevalence rates between 20% and 46% and a mean duration of 8 months. Indications for HPV typing in current clinical practice include (1) triage to colposcopy and colposcopically directed biopsy, (2) triage to conization, (3) detection of HPV persistence after conization and (4) use of HPV within primary screening programmes of cervical cancer. Available data demonstrate that HPV typing increases the sensitivity of detecting severe dysplastic lesions among women with a diagnosis of atypical cells of undetermined significance (ASCUS), but not among women with a diagnosis of low grade squamous intraepithelial lesion (LSIL). This increased sensitivity, however, seems to be equivalent to that provided by repeat cervical cytology. Infection with HPV high risk types is strongly associated with disease progression of cervical dysplasia. Cases of severe dysplasia should be treated exclusively by surgical intervention. HPV typing might aid in the selection of women with established mild or moderate dysplasia, who should also undergo surgery. Whether an HPV-based approach in this clinical setting is safe as well as cost-effective, remains unclear. There is concern, that triaging women with mild or moderate dysplasia based on their HPV status might significantly increase treatment related morbidity due to the high prevalence of HPV infections among these women Persistence of high-risk HPV infection after surgical therapy of cervical dysplasia is significantly associated with residual disease and the risk of recurrence of dysplasia. Whether routine HPV typing before and after surgical therapy of cervical dysplasia is a superior strategy compared to cytologic follow-up examinations, has not been proven. Persistent HPV infection is the most important etiologic factor of cervical cancer. Many authors have therefore proposed to incorporate HPV typing into cervical cancer screening programmes. Up to date, however, there are no clinical studies available demonstrating the safety and efficacy of HPV typing, either alone or in combination with cervical cytology, in population-based screening programmes. In summary, there is not enough evidence today to support the routine use of HPV typing in common clinical practice.

Management of the Minimally Abnormal Papanicolaou Smear in Pregnancy

Objective To evaluate the effectiveness of colposcopy of the uterine cervix in pregnant patients with minimally abnormal Papanicolaou smears. Methods Two hundred, indigent, pregnant patients with atypical cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LGSIL) on Papanicolaou smear underwent colposcopy and endocervical evaluation. Directed biopsies were performed on 64 patients. One hundred thirty-five patients were compliant with postpartum Papanicolaou smears or colposcopy with endocervical evaluation. Results One hundred eighty-seven pregnant patients had satisfactory prenatal Papanicolaou smears, colposcopy and endocervical brushings. High-grade intraepithelial lesions were found in 2.1% of prenatal endocervical brushings, 4.7% of prenatal biopsies, 0.8% of postpartum Papanicolaou smears, 2.2% of postpartum endocervical brushings, and 7.9% of postpartum biopsies. No invasive cervical cancer was detected. Conclusion Antepartum colposcopic evaluation did not add in the management of minimally abnormal Papnicolaou smears in this population of pregnant women.

Management of the Minimally Abnormal Papanicolaou Smear in Pregnancy

To evaluate the effectiveness of colposcopy of the uterine cervix in pregnant patients with minimally abnormal Papanicolaou smears. Two hundred, indigent, pregnant patients with atypical cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LGSIL) on Papanicolaou smear underwent colposcopy and endocervical evaluation. Directed biopsies were performed on 64 patients. One hundred thirty-five patients were compliant with postpartum Papanicolaou smears or colposcopy with endocervical evaluation. One hundred eighty-seven pregnant patients had satisfactory prenatal Papanicolaou smears, colposcopy and endocervical brushings. High-grade intraepithelial lesions were found in 2.1% of prenatal endocervical brushings, 4.7% of prenatal biopsies, 0.8% of postpartum Papanicolaou smears, 2.2% of postpartum endocervical brushings, and 7.9% of postpartum biopsies. No invasive cervical cancer was detected. Antepartum colposcopic evaluation did not add in the management of minimally abnormal Papnicolaou smears in this population of pregnant women.

Clinical evaluation of atypical glandular cells of undetermined significance

Objective: This study was undertaken to determine the clinical implications of the finding of atypical glandular cells of undetermined significance in cervical cytologic specimens in our patient population. Study Design: A retrospective study was performed. All cervical cytologic examinations with the diagnosis of atypical cells of undetermined significance between January 1992 and June 1997 were identified by means of a computerized database. Medical records were reviewed to identify patient demographic characteristics and to determine the presence or absence of associated pathologic conditions of the cervix and endometrium. The χ2 test and analysis of variance were applied to dichotomous and continuous variables, respectively, to determine the implications of a cytologic evaluation of atypical glandular cells of undetermined significance. Results: Cytologic results reported as atypical glandular cells of undetermined significance were obtained in a patient cohort of 492. Atypical glandular cells of undetermined significance was the only cytologic diagnosis in 224 patients; 268 patients had both atypical glandular cells of undetermined significance and an additional squamous abnormality, including atypical squamous cells of undetermined significance and cervical intraepithelial neoplasia I, II, or III. Two patients were excluded because of a history of endometrial cancer. A histologic evaluation was obtained within 1 year in 353 cases. Among the 353 patients who had a histologic evaluation performed, 227 (64%) had benign cervical and endometrial findings. There were 18 glandular lesions (5%), including complex hyperplasia with atypia, adenocarcinoma in situ of the cervix, adenocarcinoma of the cervix, and adenocarcinoma of the endometrium. A squamous lesion was present in 108 patients (31%). Most squamous lesions (81%) were found in patients with atypical glandular cells of undetermined significance associated with a squamous abnormality, whereas only 19% were found in patients with atypical glandular cells of undetermined significance as the only diagnosis. Women <35 years old had a much higher frequency of histologic abnormalities than did women >50 years old (P <.0001), with most of these lesions being squamous. Women >50 years old had a much higher frequency of glandular histologic abnormalities (P <.001). Conclusion: More than a third of women with Papanicolaou smears reported as showing atypical glandular cells of undetermined significance will be found to have a histologic abnormality. Women <35 years old with a cytologic evaluation of atypical glandular cells of undetermined significance have a higher frequency of histopathologic findings, with most being squamous lesions. Women with a cytologic evaluation of atypical glandular cells of undetermined significance who are >50 years old have more glandular lesions than do younger women. The term atypical glandular cells of undetermined significance is a misnomer. The significance of this cytologic finding has been defined and represents a marker for serious pathologic processes. (Am J Obstet Gynecol 2001;184:64-9.)

The Significance of ASCUS Cytology in HIV-Positive Women

Objective. The aim of this study was to determine the incidence and severity of dysplasia associated with a cytologic diagnosis of atypical cells of undetermined significance (ASCUS) in women infected with the human immunodeficiency virus (HIV).Methods. A cross-sectional analysis of cervical cytology, colposcopic impression, and cervical biopsy results was performed on 261 HIV-positive women diagnosed with ASCUS. The prevalence and grade of histologically documented cervical intraepithelial neoplasia (CIN) was determined. Patients with CD4 counts above and below 200 cells/mm3 were compared using χ2 analysis to determine any effect of worsening immunosuppression on the rates of associated dysplasia.Results. Seven hundred sixty-one Pap smears were performed during the study period. Two hundred nine (27%) were diagnosed as ASCUS. All patients (pts) received colposcopic evaluation. The incidence of human papilloma virus (HPV) effect, low-grade CIN (I), and high-grade CIN (II, III, and carcinoma in situ) documented by cervical biopsy, cervical conization or endocervical curettings was 40, 17, and 15%, respectively. No cases of invasive cancer were found. These results are similar to those of previous cytohistologic studies of ASCUS in HIV-untested populations. There was no significant difference in frequency or severity of CIN in pts with severe immunosuppression (P = 0.4).Conclusion. A cytologic diagnosis of ASCUS in HIV-positive women identifies a group at significant risk for histologic abnormalities. The majority of pts will be diagnosed with HPV or low-grade CIN. HIV infection and severe immunosuppression do not appear to increase the frequency or severity of CIN associated with ASCUS. Given the 32% risk of associated CIN, all HIV-positive women with ASCUS cytology should undergo colposcopic evaluation.

Characferistics of an Adolescent Cohort Undergoing Large Loop Electrosurgical Excision Procedure (LEEP)

<h3>Background</h3> LEEP is a safe and effective treatment for cervical dysplasia in adults, but its role in the management of adolescents has not been established. The objectives of this study were to describe the characteristics of a cohort of adolescents undergoing LEEP and to desaibe post-operative complications, short-term recurrence rate of high-grade squamous intraepithelial lesion (HSIL) and compliance with follow-up. <h3>Methods</h3> All 35 adolescents who underwent a LEEP between 1995 to 1997 were enrolled in this retrospective cohort. The cohort included: 29 patients with HSIL on biopsy, 4 patients with HSIL on Pap Smear and a discordant biopsy result, 1 with persistent low-grade squamous intraepithelial lesion (LSIL) and 1 with diffuse LSIL and unsatisfactory colposcopy. Data were collected through chart review. End-points included: post-operative complications, subsequent pregnancies first or second trimester spontancous abortion, recurrence of high-grade SIL (diagnosed by pre-operative biopsy or LEEP) and compliance with 3 follow-up visits over a year. A descriptive analysis was done using SPSS. <h3>Results</h3> Mean age of the subjects was 17.9 years (SD 1.5). 34% of the subjects smoked cigarettes at the time of the procedure. Only 28.6% reported use of condoms. The Pap Smear which led to referral was atypical cells of undetermined significance (ASCUS) in 25.7%. LSIL in 54.3% and HSIL in 20% of patients. The mean interval between reported age of coitarche and LEEP was 3.7 years (SD 2.1). Post-operative complications included: bleeding (5.7%). pain (2.9%), vaginal discharge (2.9%), cervicitis (8.6%) and endometritis (5.7%). Only one of the 35 patients required short-term post-operative hospitalization (endometritis). Eight pregnancies were diagnosed during the study period. One was terminated and 7 are ongoing. There were no spontancous abortions. Mean length of follow-up was 10.7 (SD 6.7) months. Of the 14 patients followed-up for greater than 12 months, there was one recurrence of HSIL in an immunocompromised patient. There were no recurrences in those patients for whom data was available (12 of the remaining 21) who were followed for less than 12 months. Follow-up compliance was 41%. <h3>Conclusions</h3> In this population of adolescents, the post-operative complication rate was low and there was no evidence of an adverse effect on fertility. The short-term recurrence rate of high-grade SIL was extremely low. Compliance with follow-up visits was 41%. LEEP appears to be a safe, effective treatment strategy for HSIL in adolescents, but additional long-term data are needed.

The "Inconclusive--possible high grade epithelial abnormality" category in Papanicolaou smear reporting.

The Australian Terminology for Cervical Cytology Reporting includes the category "Inconclusive-Possible high grade epithelial abnormality." The frequency of use of this category, the types of associated cell patterns, and the yield of high grade lesions at biopsy were studied. One hundred and two cases categorized as "Inconclusive" were reported between January and June 1995, representing 0.24% of 41,712 Papanicolaou (Pap) smears screened. The abnormal cells were reported as squamous in 74.5% of cases, endocervical in 4.9% of cases, endometrial in 3.9% of cases, and indeterminate in 16.7% of cases. The main cellular patterns included disorganized groups of hyperchromatic squamous, glandular, or indeterminate cells (64.2% of cases) and atypical metaplastic squamous cells (28.4% of cases). Cell preservation was suboptimal. In 25.3% of cases the cells were highly degenerate or air-dried. Follow-up included biopsy (84.3% of cases), colposcopy alone (7.8% of cases), and repeat Pap smears without any detected abnormality (3.9% of cases). No follow-up was available in 3.9% of cases. High grade abnormalities were found in 66.3% of the biopsied cases and 55.9% of the total cases (48 cervical intraepithelial neoplasia [CIN] of Grade 2 or 3; 2 squamous cell carcinomas; 3 endocervical adenocarcinoma in situ [ACIS]; 3 adenocarcinomas of endocervical, ovarian, and endometrial origin; and 1 endometrial stromal sarcoma). In 16.2% of cases a low grade squamous lesion was present on biopsy (CIN, Grade 1 or human papillomavirus effect); and no lesion was found in 17.4% of cases. The "Inconclusive" category was not overused, and gave a high yield of biopsy abnormalities. Accepting uncertainty in the diagnosis of some high grade lesions reduces their likelihood of being classified incorrectly as reactive changes, ignored because of poor cell preservation, or lost in the larger group of classifications such as atypical cells of undetermined significance, borderline nuclear abnormality, or non-specific minor changes.

The efficacy of two papanicolaou devices: a randomized study in a high-risk population.

Our goal was to determine the abil-ity of two Papanicolaou (Pap) smear devices to identify cor-rectly cervical intraepithelial neoplasia (CIN) in a high-risk population. Two hundred and seven nonpregnant women, referred to the colposcopy clinics at two University of Tennessee Family Practice Centers in Memphis and Jackson, were enrolled in the study if the referral Pap smear contained atypical cells of undetermined significance, a low-grade cervical intraepithelial lesion, or a high-grade intraepithelial le-sion. After they were randomly assigned to Pap smear with ei-ther the modified Ayre spatula and Cytobrush or the Acellon Combi brush, colposcopy and appropriate biopsies were per-formed in these women. Pap cytology and pathology results were compared using descriptive statistics and chi-square or Fischer's exact test. Satisfactory Pap smears were ob-tained in 91 % of the Combi brush specimens and 100% of the Ayre spatula-Cytobrush specimens. Biopsies revealed that 85% of patients had CIN. Twenty-six percent of patients had CIN2 or CIN3. The sensitivities, specificities, and false-negative rates for the identification of any CIN were 69, 73, and 31% for the Ayre spatula-Cytobrush combination, and 72, 81, and 28% for the Combi brush, respectively. The Ac-cellon Combi brush identified cervical disease as well as the spatula-Cytobrush combination in this high-risk population. The ability of a device to obtain endocervical cells did not cor-relate with its efficacy in identifying CIN.

Different risk factor patterns for high-grade and low-grade intraepithelial lesions on the cervix among HPV-positive and HPV-negative young women.

Risk factors for cervical intraepithelial neoplasia have most often been studied in high-grade lesions. Furthermore, in a high proportion of the studies, human papillomavirus (HPV), the most significant risk determinant of cervical neoplasia, was not taken into account when evaluating other risk factors. To compare risk factors for ASCUS (atypical cells of undetermined significance), LSIL (low-grade squamous intraepithelial lesion) and HSIL (high-grade squamous intraepithelial lesion), we conducted a case-control study among 20 to 29 year-old women participating in a prospective cohort study in Copenhagen. It included 131 women with ASCUS, 120 women with LSIL, 79 women with HSIL and 1,000 randomly chosen, cytologically normal, control women. All participants had a personal interview and a gynecological examination including a Pap smear and cervical swabs for HPV DNA detection using general primer-mediated polymerase chain reaction. The most significant risk determinant of all 3 disease categories was the presence of genital HPV DNA. The risk factor pattern was nearly identical for ASCUS and LSIL, but differed significantly from that for HSIL. Stratified analysis by HPV-status showed that, apart from, respectively, smoking and parity among HPV-positive women, and smoking and number of sex partners among HPV-negative women, no additional risk factors were observed for ASCUS and LSIL. In contrast, among HPV-negative women with HSIL, long-term use of oral contraceptives was the most important risk factor. However, our result should be taken with great caution as it is based on very small numbers, and as it is unknown whether the HPV-negative lesions constitute a true entity. Among HPV-positive women, the risk of HSIL was associated with e.g., years of sex life without barrier contraceptive use, early age at first genital warts and smoking. Whether the risk factors that are applicable only to HSIL represent factors related to progression remains unknown.

Different risk factor patterns for high‐grade and low‐grade intraepithelial lesions on the cervix among HPV‐positive and HPV‐negative young women

Risk factors for cervical intraepithelial neoplasia have most often been studied in high-grade lesions. Furthermore, in a high proportion of the studies, human papillomavirus (HPV), the most significant risk determinant of cervical neoplasia, was not taken into account when evaluating other risk factors. To compare risk factors for ASCUS (atypical cells of undetermined significance), LSIL (low-grade squamous intraepithelial lesion) and HSIL (high-grade squamous intraepithelial lesion), we conducted a case-control study among 20 to 29 year-old women participating in a prospective cohort study in Copenhagen. It included 131 women with ASCUS, 120 women with LSIL, 79 women with HSIL and 1,000 randomly chosen, cytologically normal, control women. All participants had a personal interview and a gynecological examination including a Pap smear and cervical swabs for HPV DNA detection using general primer-mediated polymerase chain reaction. The most significant risk determinant of all 3 disease categories was the presence of genital HPV DNA. The risk factor pattern was nearly identical for ASCUS and LSIL, but differed significantly from that for HSIL. Stratified analysis by HPV-status showed that, apart from, respectively, smoking and parity among HPV-positive women, and smoking and number of sex partners among HPV-negative women, no additional risk factors were observed for ASCUS and LSIL. In contrast, among HPV-negative women with HSIL, long-term use of oral contraceptives was the most important risk factor. However, our result should be taken with great caution as it is based on very small numbers, and as it is unknown whether the HPV-negative lesions constitute a true entity. Among HPV-positive women, the risk of HSIL was associated with e.g., years of sex life without barrier contraceptive use, early age at first genital warts and smoking. Whether the risk factors that are applicable only to HSIL represent factors related to progression remains unknown. Int. J. Cancer 76:613–619, 1998.© 1998 Wiley-Liss, Inc.

Assessment of cytologic follow-up as the recommended management for patients with atypical squamous cells of undetermined significance or low grade squamous intraepithelial lesions

The optimal management of low grade Papanicolaou (Pap) smear abnormalities remains controversial. This center's experience with recommending cytologic follow-up for women with atypical cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesions (LSIL) was reviewed to determine outcome and patient/physician compliance. The records were reviewed on women with Pap smears reported as either ASCUS (320) or LSIL (112) who did not have a history of dysplasia. The cytologic and colposcopic follow-up for a 2-year period was obtained from the laboratory data base that includes the colposcopy and cancer referrals for this region. Repeat Pap smear in 6 months was recommended. If patients subsequently demonstrated high grade SIL (HSIL) or persistent ASCUS or LSIL over three time intervals, colposcopic evaluation was recommended. The outcome was determined by the most significant diagnosis among the follow-up Pap smears or colposcopic biopsies. 29% of patients were lost to follow-up. Of the remaining patients, 70.5% reverted to normal or benign cellular changes, 25.3% persisted as ASCUS or LSIL, and 5.2% progressed to HSIL. The majority of patients (68%) were referred for colposcopy for persistent mildly abnormal Pap smears. The timing of referral ranged from 3-30 months. These results suggest that cytologic follow-up of women with low grade Pap smear abnormalities will identify a large number whose smears will regress to normal. A small but significant proportion of women showed subsequent HSIL. Most HSIL was detected within 1 year of the initial abnormal Pap smear and the majority of intervening Pap smears also were abnormal. Approximately one third of patients did not have follow-up within the study system and their outcome was uncertain. Although the recommendations are standard, patterns of follow-up and referral to colposcopy varied widely, suggesting that the guidelines need to be reinforced to both patients and physicians. [See editorial on pages 1-4, this issue.]