High-grade Squamous Intraepithelial Lesion Cytology Research Articles

Human papillomavirus type distribution in women from Asia: a meta-analysis

The aim of this study was to determine human papillomavirus (HPV) type distribution in women with and without cervical neoplasia from Asia and to estimate the potential future impact of an HPV 16/18 prophylactic vaccine in this region. A meta-analysis was conducted including 79 studies using polymerase chain reaction to detect HPV types. A total of 5954, 1653, 958, and 16,803 women with invasive cervical cancer (ICC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), and normal cytology or histology were included, respectively. Type-specific prevalence of HPV types 6, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73, and 82 were estimated and stratified by cervical lesion grade. Overall HPV prevalence was 85.9%, 81.0%, 72.9%, and 14.4%, respectively, in women with ICC, HSIL, LSIL, and normal cytology/histology. In ICC, HPV 16 was the predominant type (52.4%), followed by HPV 18, 58, 33, 52, 45, 31, and 35. The estimated HPV 16/18–positive fraction was 66.9%, 40.4%, 26.7%, and 3.3% in women with ICC, HSIL, LSIL, and normal cytology or histology, respectively. In ICC, the estimated HPV 16/18–positive fraction was about 70% in all Asian geographic regions, with the exception of Japan (51.3%). HPV 16/18 vaccines are estimated to provide about 67% protection against ICC in Asia. HPV 58 and 52 were among the five most common types in ICC in eastern and southeastern Asia but not in south central Asia. After HPV 16 and 18, the next most six common HPV types were 58, 33, 52, 45, 31, and 35 that accounted for additional 20% of cervical cancer cases in Asia. For optimal population coverage, these HPV carcinogenic types should be considered for second-generation HPV prophylactic vaccines.

Chromosomal Biomarkers for Detection of Human Papillomavirus Associated Genomic Instability in Epithelial Cells of Cervical Cytology Specimens

The goal of this study was to compare how accumulation of chromosomal aberrations in human papillomavirus (HPV)-infected cells correlates with the severity of cervical dysplastic lesions. We assessed the frequency of genomic alterations for 35 different loci in a pilot biopsy study and selected two loci (3q26 and 8q24) with the highest frequency of copy number gains found in high-grade dysplasia and cancer. These probes were labeled with gold and red fluorophores and combined with HPV biotin-labeled probes for subsequent detection using a tyramide signal amplification system with a green fluorophore. Cells that were both HPV positive and chromosomally abnormal were designated as "double-positive cells." Cervical cytology specimens from 235 patients were used for this blinded study. The average number of double-positive cells increased from two cells in patients with a cytological interpretation of atypical squamous cells of undetermined significance to 22 cells in low-grade squamous intraepithelial lesion and 99 cells in high-grade squamous intraepithelial lesion, reflecting an accumulation of chromosomal abnormality with disease progression. Using a cutoff of four or more double-positive cells as the criterion for the presence of a cervical intraepithelial neoplasia 2 or 3 lesion, we demonstrated that low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion cytology specimens with underlying cervical intraepithelial neoplasia 2/3 histology showed positive test results in more than 80% of cases. Correlation of 3q26 and 8q24 aneusomy with concurrent HPV infection may thus serve as a biomarker of genetic instability in HPV-infected cells.

Evaluation of candidate methylation markers to detect cervical neoplasia

Objective. Studies of cervical cancer and its immediate precursor, cervical intraepithelial neoplasia 3 (CIN3), have identified genes that often show aberrant DNA methylation and therefore represent candidate early detection markers. We used quantitative PCR assays to evaluate methylation in five candidate genes (TNFRSF10C, DAPK1, SOCS3, HS3ST2 and CDH1) previously demonstrated as methylated in cervical cancer. Methods. In this analysis, we performed methylation assays for the five candidate genes in 45 invasive cervical cancers, 12 histologically normal cervical specimens, and 23 liquid-based cervical cytology specimens confirmed by expert review as unequivocal demonstrating cytologic high-grade squamous intraepithelial lesions, thus representing the counterparts of histologic CIN3. Results. We found hypermethylation of HS3ST2 in 93% of cancer tissues and 70% of cytology specimens interpreted as CIN3; hypermethylation of CDH1 was found in 89% of cancers and 26% of CIN3 cytology specimens. Methylation of either HS3ST2 or CDH1 was observed in 100% of cervical cancer tissues and 83% of CIN3 cytology specimens. None of the five genes showed detectable methylation in normal cervical tissues. Conclusion. Our data support further evaluation of HS3ST2 and CDH1 methylation as potential markers of cervical cancer and its precursor lesions.

Human papillomavirus type distribution in women from Asia: a meta-analysis

The aim of this study was to determine human papillomavirus (HPV) type distribution in women with and without cervical neoplasia from Asia and to estimate the potential future impact of an HPV 16/18 prophylactic vaccine in this region. A meta-analysis was conducted including 79 studies using polymerase chain reaction to detect HPV types. A total of 5954, 1653, 958, and 16,803 women with invasive cervical cancer (ICC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), and normal cytology or histology were included, respectively. Type-specific prevalence of HPV types 6, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73, and 82 were estimated and stratified by cervical lesion grade. Overall HPV prevalence was 85.9%, 81.0%, 72.9%, and 14.4%, respectively, in women with ICC, HSIL, LSIL, and normal cytology/histology. In ICC, HPV 16 was the predominant type (52.4%), followed by HPV 18, 58, 33, 52, 45, 31, and 35. The estimated HPV 16/18-positive fraction was 66.9%, 40.4%, 26.7%, and 3.3% in women with ICC, HSIL, LSIL, and normal cytology or histology, respectively. In ICC, the estimated HPV 16/18-positive fraction was about 70% in all Asian geographic regions, with the exception of Japan (51.3%). HPV 16/18 vaccines are estimated to provide about 67% protection against ICC in Asia. HPV 58 and 52 were among the five most common types in ICC in eastern and southeastern Asia but not in south central Asia. After HPV 16 and 18, the next most six common HPV types were 58, 33, 52, 45, 31, and 35 that accounted for additional 20% of cervical cancer cases in Asia. For optimal population coverage, these HPV carcinogenic types should be considered for second-generation HPV prophylactic vaccines.

Comparison of the SPF 10 -LiPA System to the Hybrid Capture 2 Assay for Detection of Carcinogenic Human Papillomavirus Genotypes among 5,683 Young Women in Guanacaste, Costa Rica

The objective of this analysis was to compare the performance characteristics of two human papillomavirus (HPV) DNA detections assays, the Hybrid Capture 2 assay (HC2) and the SPF(10) assay, for the detection of carcinogenic HPV. Data are from the enrollment visits of women who participated in the randomized, double-blind, placebo-controlled phase III HPV16/18 Vaccine Trial in Guanacaste, Costa Rica. We compared the results of HC2 and SPF(10) testing of cervical specimens. Since the line probe assay (LiPA) detection system does not distinguish between HPV type 68 (HPV68; which is targeted by HC2) and HPV73 (which is not targeted by HC2), for SPF(10)-LiPA, we defined the carcinogenic HPV types as the 12 HC2-targeted types (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), HPV68/73, and the HC2-cross-reactive, carcinogenic type HPV66. The kappa values and the performance characteristics for the detection of cervical abnormalities were ascertained. Paired observations were available for 5,683 sexually active, young women (median age, 21 years). The prevalence of carcinogenic HPV types was 35% (n=1,962) by HC2 and 35% (n=2,003) by SPF(10)-LiPA. There were no differences in the prevalence of carcinogenic HPV types by HC2 and SPF(10)-LiPA among women with normal, atypical squamous cells of undetermined significance and high-grade squamous intraepithelial lesion cytology. Among women with low-grade squamous intraepithelial lesion cytology, HC2 was more likely to test positive than SPF(10)-LiPA for the carcinogenic HPV types (87% and 79%, respectively; P=0.001) as a result of HC2 cross-reactivity with HPV types 40, 43, 44, 53, 54, 60, 70, and 74. The crude agreement between the two assays was 88%, with a kappa value of 0.75 (95% confidence limits, 0.73 to 0.76). We observed very good agreement between HC2 and SPF(10)-LiPA for carcinogenic HPV type detection.

Treatment of high-grade squamous intraepithelial lesions: A “see and treat” versus a three-step approach

ObjectiveThe study's subject was to examine the correlation between histologic findings in patients with high-grade squamous intraepithelial lesion (HGSIL) who have undergone loop electrosurgical excisional procedure (LEEP) with and without prior colposcopically directed biopsy. StudydesignThis retrospective study included 144 patients with cytologic HGSIL, of which 62 were treated by a three-step protocol, in which LEEP was performed only if the colposcopically directed cervical biopsies were positive (CIN II–III), and 82 women who were treated by “see and treat” protocol, in which LEEP was immediately performed if colposcopy was suggestive of CIN II or III lesions. ResultsThere were no differences in the final histological findings between the groups. ConclusionsThe colposcopically directed LEEP after a HGSIL on PAP-smear may reduce the time interval between diagnosis and treatment with a similar accuracy of diagnosis compared to the standard three-step protocol.

Cervical Dysplasia in Adolescents

Although the incidence of cervical dysplasia in adolescents is increasing, a paucity of data exists regarding the outcomes of adolescents with Pap test abnormalities. We determined the natural history and outcome of adolescents with low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). A review of all women aged 18 years or younger with a cytologic diagnosis of LSIL or HSIL between 1997 and 2003 was performed. Follow-up cytologic and histologic samples were evaluated. The most significant abnormality was recorded for each patient. Rates of regression, persistence, and progression were calculated. A total of 646 adolescents were identified. Follow-up was available for 477 teenagers with LSIL and for 55 with HSIL. Among adolescents with LSIL, 146 (35%) had negative follow-up. Low-grade abnormalities (atypical squamous cells of undetermined significance, LSIL, and cervical intraepithelial neoplasia grade 1) were seen in 199 (47%), whereas high-grade abnormalities were documented in 77 (18%). After 36 months, 62% had regressed, whereas 31% had progressive dysplasia. For the HSIL cohort, negative follow-up was documented in 12 (21.8%) adolescents, and 15 (27.3%) had low-grade abnormalities, whereas more than one half (50.9%) were found to have a high-grade abnormality. At 36 months, 31% of HSIL subjects had progressed to cervical intraepithelial neoplasia 3. Adolescents with LSIL and HSIL cytology are at significant risk for progression to high-grade cervical abnormalities. The rate of development of high-grade cervical abnormalities in adolescents is similar to adults. Adolescents with cytologic abnormalities mandate close follow-up. II-3.

Should Liquid-Based Cytology Be Repeated at the Time of Colposcopy?

Five thousand one hundred women age 18–50 years participated in a cervical cancer screening program using liquid-based cytology and human papillomavirus (HPV) DNA testing. Women with abnormal cytology testing, including atypical squamous cells of undetermined significance (ASCUS), or HPV DNA results positive for high-risk HPV types were referred for colposcopic examination. For this study, the liquid-based cytology was repeated at the time of colposcopy to determine the value of repeat screening. The cytology results of the initial screening for 5100 women found 3.3% with high-grade squamous intraepithelial lesions (HSIL), 4.3% with low-grade squamous intraepithelial lesions (LSIL), 9.7% ASCUS, 0.1% atypical glandular cells of unknown significance (AGUS), and 1.3% inadequate smear. Nineteen percent of patients tested positive for high-risk HPV types. In all, 870 women had abnormal cytology at the initial screening; 644 returned for colposcopy. Of 818 women who had negative Pap smear results but were positive for high-risk HPV, 433 returned for colposcopy. In addition, 245 women with normal cytology and negative HPV results agreed to undergo voluntary colposcopy and served as controls. In all, including 18 women with unsatisfactory or missing cytology and positive HPV results, 1340 women underwent colposcopic examination and 1333 had colposcopically directed biopsy. Women with negative or atypical histology, or women whose histologic specimen showed cervical intraepithelial neoplasia (CIN) 1, were referred back to their health clinics. Women who had CIN 2, 3, or adenocarcinoma-in-situ were advised to have the loop electrical excision procedure (LEEP) or cervical conization. Women in whom cancer was found were referred to a gynecologic oncologist for further care. Three cancers were identified in this study population; all were found in the initial screening smear. Among 153 women with HSIL cytology results at colposcopy, biopsy results showed CIN 2 or 3 in 104 (68%) and CIN 1 in 18 (12%). There were 30 women with HSIL cytology results at colposcopy who had negative or atypical histology results. Screening cytology was positive for HSIL in 9 of these patients, but there were 21 women whose initial cytology results and whose biopsy results were negative for high-grade disease. These women were advised to undergo excisional treatment for a high-grade lesion. They are the only patients for whom repeated cytology changed the course of clinical management. The results of the initial Pap smear and the smear taken at colposcopy were compared according to the interval of time between the 2. Among the 21 women with a discrepancy found between initial screening and repeat cytology, 9 were among 686 (1.31%) women who returned for colposcopy within 60 days of the initial screening, 8 were among 509 patients (1.57%) who had colposcopy 61 to 180 days after initial screening, and 4 were among 139 women (2.88%) with more than 180 days between initial screening and colposcopic examination (P for trend = 0.12, not significant).

Evaluation of cytologic screening results of the cervix

The aim of this study was to evaluate retrospectively cytologic screening for cancers and precancerous lesions of the cervix and to research whether biopsy is overused among women with a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS). We examined 28 469 smears obtained over 5 years. The patients were referred when the result of the smear was abnormal for a colposcopic biopsy, endocervical curettage, or a repeat Papanicolaou smear. The results of the screening of 28 469 smears are as follows: 699 (2.45%) ASCUS, 67 (0.23%) low-grade squamous intraepithelial lesions (LGSIL), 43 (0.15%) high-grade squamous intraepithelial lesions (HGSIL), 1 epidermoid carcinoma, 31 (0.10%) atypical glandular cells, and 1 adenocarcinoma. Histologic examination of the cervix was done in 119 patients (17.0%) of ASCUS, 13 patients (10.9%) of LGSIL, and 15 patients (12.6%) of HGSIL and cervical carcinoma. In the 119 women with histological examination, histologic examination was generally performed in patients with ASCUS neoplastic Papanicolaou smear, and histologic diagnosis of low-grade, high-grade, or invasive lesion of the cervix was made in 23.5% of women with ASCUS; in these patients, 46.4% were cytologic LGSIL and 53.5 % were cytologic HGSIL and cervical carcinoma. In the aspect of these findings, we concluded that for patients with a cytologic diagnosis of ASCUS, more aggressive interventions should be performed.

Evaluation of cytologic screening results of the cervix

The aim of this study was to evaluate retrospectively cytologic screening for cancers and precancerous lesions of the cervix and to research whether biopsy is overused among women with a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS). We examined 28 469 smears obtained over 5 years. The patients were referred when the result of the smear was abnormal for a colposcopic biopsy, endocervical curettage, or a repeat Papanicolaou smear. The results of the screening of 28 469 smears are as follows: 699 (2.45%) ASCUS, 67 (0.23%) low-grade squamous intraepithelial lesions (LGSIL), 43 (0.15%) high-grade squamous intraepithelial lesions (HGSIL), 1 epidermoid carcinoma, 31 (0.10%) atypical glandular cells, and 1 adenocarcinoma. Histologic examination of the cervix was done in 119 patients (17.0%) of ASCUS, 13 patients (10.9%) of LGSIL, and 15 patients (12.6%) of HGSIL and cervical carcinoma. In the 119 women with histological examination, histologic examination was generally performed in patients with ASCUS neoplastic Papanicolaou smear, and histologic diagnosis of low-grade, high-grade, or invasive lesion of the cervix was made in 23.5% of women with ASCUS; in these patients, 46.4% were cytologic LGSIL and 53.5 % were cytologic HGSIL and cervical carcinoma. In the aspect of these findings, we concluded that for patients with a cytologic diagnosis of ASCUS, more aggressive interventions should be performed

Comparison of Human Papillomavirus Messenger RNA and DNA Detection: A Cross-sectional Study of 4,136 Women >30 Years of Age with a 2-Year Follow-up of High-Grade Squamous Intraepithelial Lesion

The purpose of this study was to compare the detection of human papillomavirus (HPV) DNA with detection of mRNA. The study included 4,136 women >30 years of age. E6/E7 mRNA expression from the carcinogenic HPV types 16, 18, 31, 33, and 45 was detected by the PreTect HPV-Proofer assay, whereas the presence of HPV DNA was detected by Gp5+/6+ consensus PCR followed by type-specific PCR. A total of 4.0% had an abnormal cytologic diagnosis, 3.0% were positive by PreTect HPV-Proofer, 4.4% by type-specific PCR, and 10.4% by consensus PCR. For detection of HPV in high-grade squamous intraepithelial lesion (HSIL), no significant difference was observed between PreTect HPV-Proofer and consensus PCR. For women with a cytologic normal, atypical squamous cell of uncertain significance, and low-grade SIL diagnosis, the detection rate of HPV was significantly higher by Gp5+/6+ consensus PCR (P < 0.005) than by PreTect HPV-Proofer. Histology confirmed 14 of 23 cytologic HSIL as cervical intraepithelial neoplasia grade >2. Of these women, PreTect HPV-Proofer and type-specific PCR detected 12, whereas consensus PCR detected 13. In conclusion, for HSIL, detection of E6/E7 transcripts from HPV types 16, 18, 31, 33, and 45 are present to the same degree as DNA detected by consensus PCR. Equally important, only a small proportion of the HPV DNA-positive women with a normal, atypical squamous cell of uncertain significance or low-grade SIL diagnosis had a detectable mRNA expression. HPV E6/E7 mRNA detection by PreTect HPV-Proofer represents a new promising test as an adjunct to cytology.

Evidence Supporting the Current Management Guidelines for High-Grade Squamous Intraepithelial Lesion Cytology

The study was undertaken to provide consensus guidelines for the management of women with a cytologic interpretation of high-grade squamous intraepithelial lesion (HSIL) on cytologic examination. This review article presents relevant literature supporting the proposed guidelines. 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. Guidelines for the management of women with HSIL cytologic results were developed through a multistep process. Draft management guidelines were developed by the HSIL working group after formal literature reviews and obtained input from the professional community at large by way of an interactive internet-based bulletin board. At the American Society for Colposcopy and Cervical Pathology Consensus Conference, September 6 through 8, 2001, in Bethesda, Maryland, the guidelines were discussed, revised, and adopted by formal vote. Evidence-based guidelines have been developed for the management of women with HSIL cytologic results.

High-grade cervical squamous intraepithelial lesion during pregnancy.

An increasing incidence of high-grade squamous intraepithelial lesion (HSIL) has been observed among young women. Consequently, an increased number of cases are being discovered during pregnancy. We analyzed the clinical and therapeutic management of HSIL during pregnancy. A retrospective study was conducted from 1979 to 1998, and 58 registries of women with a cytological or histological diagnosis of HSIL during the pregnant-puerperal period were reviewed. Information obtained from medical records included age, gestational age at diagnosis, parity, age of first intercourse, number of sexual partners before pregnancy, tobacco use, cytologic and colposcopic findings, route of delivery, postpartum follow-up, and treatment. This information was compared with a non-pregnant control group with HSIL. The average age of pregnant women with HSIL was 27.9 +/- 5.2 years. The cytologic or histologic diagnosis of HSIL was made in the first trimester in 12 (20.7%) women and in the second trimester in 30 (51.7%) women. Average parity was 2.8 +/- 2 deliveries. Age of first intercourse ranged from 13 to 29 years (16.1 +/- 3.3). Thirty-two women (55.1%) had more than one sexual partner before pregnancy. Thirty-seven (63.8%) refereed tobacco use. According to the aforementioned aspects, no statistical difference was found in relation to control, except to cervical ectopia, which was more frequent in pregnant women (56.9% versus 42.6%). From the total of 58 pregnant women with cytologic or biopsy HSIL diagnosis, 53 had HSIL diagnosis made on cervical biopsy directed by colposcopy performed during the pregnancy; 44 (83%) of them were submitted to conservative management. HSIL was diagnosed by cervical biopsy in postpartum evaluation in 76% pregnant women with vaginal delivery and 78.6% women who underwent cesarean section. A conservative management of HSIL in pregnancy is proposed, with colposcopic evaluation during gestation and postpartum, regardless of route of delivery.

2001 Consensus Guidelines for the Management of Women with Cervical Cytological Abnormalities

EACH YEAR APPROXIMATELY 50 million women undergo Papanicolaou testing in the United States. Of these, approximately 3.5 million (7%) are diagnosed with a cytological abnormality requiring additional follow-up or evaluation. Determining which women with cytological abnormalities are at risk for significant cervical disease, performing appropriate diagnostic workups, and treating cancer precursors present a major public health challenge. There are a number of reasons why comprehensive, evidence-based guidelines are needed for the management of women with cervical cytological abnormalities. One reason is that a National Cancer Institute workshop recently revised the criteria used by cytologists to render certain cytological interpretations, as well as the terminology used for reporting cervical cytology results (ie, the Bethesda System). Other reasons include a better understanding of the pathogenesis and natural history of human papillomavirus (HPV) and cervical cancer precursors, and the availability of data from the National Cancer Institute’s randomized Atypical Squamous Cells of Undetermined Significance/Low-grade Squamous Intraepithelial Lesion (ASCUS/LSIL) Triage Study (ALTS) (D. Solomon, MD, written communication, September 6-8, 2001). Moreover, existing guidelines were developed before sensitive molecular methods for detecting high-risk types of HPV and liquid-based cytology methods became widely available. Data are now available suggesting that these new technologies, when used together, are attractive alternatives to older approaches for managing women with cer-

Does Liquid-Based Technology Really Improve Detection of Cervical Neoplasia?

To compare the sensitivity, specificity and specimen adequacy of the ThinPrep Pap Test (TP) with the conventional Pap Test (CV) in a low-risk population with subsequent follow-up of HSIL cases. A prospective, randomized, controlled design was chosen to compare the TP with CV. Cytologic diagnosis and specimen adequacy were evaluated and compared with histology data in high grade squamous intraepithelial lesion (HSIL) cases. Fifteen gynecologists in private practice, all trained in colposcopy, participated in the trial. Cytologic diagnosis, specimen adequacy and follow-up of the cytologic HSIL cases were compared in the two groups. In total, 1,999 patients were included, 997 in the TP group and 1,002 in the CV group. Randomization assignments were designated on cytology case report forms, which were placed in sealed envelopes. Each envelope had a sequential randomization number on the outside to allow tracking and authentication of randomization assignments. Comparison of results between CVs and TPs revealed no statistically significant differences in all diagnostic categories, ranging from "within normal limits" to HSIL. Specimen adequacy, however, was superior with CVs (P < .001). The cytologic diagnosis of HSIL correlated with the histologic diagnosis in 91% of the TP group and 100% of the CV group. Because there was no statistically significant difference in sensitivity and specificity of the two techniques, improved detection of cervical abnormalities and better specimen adequacy might not be a consequence of utilizing liquid-based preparations but of a better sampling technique. Removing mucus and cellular debris from the cervical surface with a cellulose swab before sampling cells with a proper sampling device results in the same sensitivity and specimen adequacy and is much less expensive than the liquid-based technique.

Role of HPV Testing in Secondary and Primary Screening of Cervical Neoplasia

To evaluate the performance of HPV testing in identifying cervical neoplasia. Minor cytologic atypia of the uterine cervix, particularly atypical squamous cells of undetermined significance (ASCUS) represent a vast group, at least three times more frequent than cytologic high-grade squamous intraepithelial lesions (HGSIL). Even though, individually, ASCUS smears correspond to a normal cervix in nearly 80% of cases, their marked prevalence in the screened population suggests that this category of smear is one of the main sources of histologically confirmed high-grade SIL.The recent recommendations by the National Agency of Accreditation and Evaluation (ANAES) for managing ASCUS smears indicate that it is possible to advise a follow-up smear at regular intervals or immediate colposcopy. The follow-up smear option has limitations related to its incomplete sensitivity (25-40% of existing high-grade SIL can go unrecognized). Colposcopy has optimal sensitivity in recognizing high-grade lesions, but falls short due to lack of specificity.The Hybrid Capture (HC II) (Digene, Silver Spring, MD) test is an objective and reproducible test that makes it possible to detect nononcogenic and oncogenic types of human papillomavirus (HPV) and the DNA viral load, thereby increasing the probability that significant cervical lesions will not go unrecognized. The Hybrid Capture test is simple to perform and positive results for high-risk HPV strongly correlate with the presence of high-grade CIN (sensitivity of approximately 98%). The test's nearly 100% negative predictive value makes it possibly to fully reassure patients who have had an ASCUS smear, freeing them from regular cytologic follow-up, colposcopy, and biopsy. A Hybrid Capture II test that is positive for oncogenic HPV significantly increases the probability of recognizing significant, precancerous cervical lesions. When the reference smear has been done in a liquid suspension, the Hybrid Capture test can be done on the residual cells in the suspension, thereby avoiding an additional visit. Recent French and international evaluations and publications should encourage the ANAES task force to propose the HPV test as a possible option for managing smears with minor atypia.▪.

Potential hazards of following atypical and low-grade cervical cytology without colposcopy

Objective: To determine the frequency of high-grade cervical intraepithelial neoplasia in patients with atypical and low-grade cervical cytology and to assess the optimal evaluation and follow-up. Methods: Prospective observational study of 367 of 7,651 private patients who had cytologic, virologic, or colposcopic changes suggesting cervical intraepithelial neoplasia or cervical carcinoma. The study was performed to determine the frequency of cervical intraepithelial neoplasia in the various cytologic groups and to assess the effect of testing for human papillomavirus on the sensitivity, specificity, and positive predictive value of these tests. Results: Papanicolaou smears that included all non-negative tests (high- and low-grade squamous intraepithelial lesions and atypical squamous or glandular epithelial cells of undetermined significance) had the maximal sensitivity (89%) for high-grade cervical intraepithelial neoplasia and cancer. The combined cytologic categories of high- and low-grade squamous intraepithelial lesions had a sensitivity of 58%, this was reduced to 24% if only high-grade squamous intraepithelial lesions were considered relevant for additional evaluation. If we had not evaluated the patients with atypical squamous and glandular cells of undetermined significance, we would have missed diagnosing one third of high-grade and one half of low-grade cervical intraepithelial neoplasia. Cervical cytology was false negative in 8% of patients with high-grade and in 14% of those with low-grade cervical intraepithelial neoplasias. High-risk human papillomavirus deoxyribonucleic acid was detected in 40% of women with high-grade and in 24% of those with low-grade grade cervical intraepithelial neoplasias. The positive predictive value of cytology with atypical squamous cells of undetermined significance increased from 5% to 38% for high-grade and from 30 to 85% for high- and low-grade cervical intraepithelial neoplasias in patients with detectable high-risk human papillomavirus deoxyribonucleic acid. Virologic studies produced no significant improvement on these diagnoses in women with high- or low-grade cytology. Conclusions: Because of the poor sensitivity of cytology suggesting high-grade squamous intraepithelial lesions, we recommend that all women with atypical or low-grade cytology be recalled for colposcopy and high-risk human papillomavirus deoxyribonucleic acid testing, if available. Decisions whether to perform a biopsy should be based on the result of colposcopic examination. Performing colposcopy only on those patients who have cytologic high-grade squamous intraepithelial lesions and following those with lower grade cytologic anomalies without colposcopic diagnosis appears inadequate to rule out high-grade cervical intraepithelial neoplasia.