Management of women with cervical cancer precursor lesions

An understanding of the natural history of HPV-induced precancer and cancer, and of the immune response to HPV and to these lesions, has significantly changed the management of lower genital tract neoplasia. New management guidelines incorporate this understanding, providing a more rational approach to diagnosis and treatment. Understanding that low-grade HPV-induced lesions are not true cervical cancer precursor has fostered expectant management of women with these lesions; however, management approaches are still hampered by the inability to better predict who is at risk for high-grade intraepithelial neoplasia and cancer and who is not; this is particularly problematic in the expectant management of CIN 1. In addition, the decision whether or not to treat these low-grade lesions may depend on a number of complex factors that take into account the woman's preferences and reliability for follow-up, as well as a host of issues related to costs and the reliability of the original diagnosis and the tests used for follow-up. Management options for high-grade cervical cancer precursor lesions are much more definitive, because the option of expectant management is given except in pregnancy and for adolescents with CIN 2. New markers that better predict which women with high-risk HPV are at highest risk for subsequent development of a true cervical cancer precursor lesion appear to be on the horizon and may make the management of low-grade lesions as clear as present guide lines for their high-grade cousins. Until that time, understanding all the issues involved in expectant and in active management of cervical HPV-induced lesions will help provide women with the best care possible.     

High-risk human papillomavirus DNA testing and high-grade cervical intraepithelial lesions

OBJECTIVE: To explore the role of high-risk human papillomavirus (HPV) DNA testing in the improvement of the recognition of cervical cancer and precancerous lesions in women with abnormal cervical cytology. METHODS: A total of 2152 women with abnormal cervical cytology were submitted to both HPV DNA testing and biopsy guided by colposcopy and the results were correlated. RESULTS: Positive rate of high-risk HPV DNA in groups of atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells, cannot exclude high-grade (ASC-H), low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions was 53.7, 53.2, 84.6 and 93.0%, respectively. In each group, the detection rate of grade 2,3 cervical intraepithelial neoplasia (CIN 2,3) or cervical cancer in patients with positive HPV DNA was significantly higher than that with negative HPV DNA (P<0.05). In ASC-US group, the negative predictive value of high-risk HPV DNA testing for detection of CIN 2,3 and cervical cancer was 99.8% and the sensitivity 98%. CONCLUSION: HPV DNA testing is a useful indicator in the management of patients with ASC-US and plays an important role in the evaluation of risk for CIN 2,3 and cervical cancer.     

Guidelines for screening and treatment of cervical disease in the adolescent

BACKGROUND: The last decade has seen a significant increase in our knowledge of HPV infection and its natural history. The advent of liquid-based cytology and HPV testing has changed the way we approach patients with abnormal Pap tests. The objective is to summarize some of the key evidence that lead to the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines for the management of abnormal cytology and histology and the American Cancer Society (ACS) cervical cancer screening guideline as they pertain to adolescents. METHODS: The critical publications responsible for the recent ASCCP guidelines as well as the ACS recommendations for cervical cancer screening were reviewed. RESULTS: Sexually active adolescents are frequently infected by HPV. The natural history of these infections is one with a high rate of resolution. The typical HPV infection will resolve in approximately one year. The ACS has recommended that Pap test screening begin at 21, or 3 years after the onset of sexual activity. The ASCCP guidelines for the management of CIN 1 conclude that observation is the preferred therapy. These recommendations reflect our improved understanding of the natural history of HPV infection. CONCLUSIONS: Adolescents frequently experience transient HPV infections. As our understanding of the natural history of these infections has improved major national organizations have changed the recommendations for the screening of cervical disease and treatment of low-grade cervical abnormalities. The health care community servicing adolescents should incorporate these recommendations into daily practice.     

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.     

Diagnoses and outcomes in cervical cancer screening: a population-based study

OBJECTIVE: This study was undertaken to examine routine cervical cancer screening diagnoses and outcomes on an age-specific basis in a US population. STUDY DESIGN: We conducted an observational cohort study using 1997-2002 health plan administrative and laboratory data for women enrolled at Kaiser Permanente Northwest (Portland, Ore) in 1998. RESULTS: Across all female enrollees (n=150,052), the annual rate of routine cervical cancer screening was 294.7 per 1,000, with cytologic abnormalities detected at a rate of 14.9 per 1,000. The annual incidence of cervical intraepithelial neoplasia (CIN) 1 was 1.2 per 1,000 with a rate of 1.5 per 1,000 for CIN 2/3. CIN 1 incidence peaked among women aged 20 to 24 years (5.1 per 1,000), with CIN 2/3 rates highest among those 25 to 29 years (8.1 per 1,000). From among 44,493 routine cervical smears, results were normal for 94.5%, with abnormal diagnoses of atypical squamous cells (3.3%), atypical glandular cells (0.2%), low-grade squamous intraepithelial lesion (1.2%), high-grade squamous intraepithelial lesion (0.3%), and inconclusive/inadequate (0.5%). Of women with abnormal routine smears, CIN or cancer was detected on follow-up in 19.4% of cases, 51.5% were found to have had a false-positive smear, and 29.0% incomplete follow-up as defined by published management guidelines. CONCLUSION: These are the first comprehensive age-specific estimates of routine cervical cancer screening diagnoses and outcomes to be reported within a US general healthcare setting. Overall, 5% of routinely screened women were found to have an abnormal cervical smear with an annual incidence of CIN across all female enrollees of 2.7 per 1000.     

Atypical squamous cells of undetermined significance in girls and women

OBJECTIVE: To estimate the outcome of adolescents with atypical squamous cells of undetermined significance (ASC-US) on cytology. METHODS: A review of ASC-US cytology in girls and women aged 10-19 years between 1995 and 1999 was performed. The cytologic and histologic follow-up of each patient was evaluated. The outcome was recorded as the most significant (highest grade) subsequent cervical smear or biopsy. RESULTS: Overall, 535 of 7897 (6.8%) cervical cytologic specimens were reported as ASC-US. The study group consisted of 398 patients for whom pathologic follow-up was available. The mean duration of follow-up was 19 months. Follow-up consisted of repeat cytology in 251 (63%) patients and colposcopy with cervical biopsies and/or endocervical curettage in 147 (37%) of the adolescents. Two hundred fifty-three (64%) adolescents had no pathologic abnormalities on follow-up. Persistent ASC-US was identified in 65 (16%), low-grade squamous intraepithelial lesions/cervical intraepithelial neoplasia (CIN) 1 was found in 44 (11%) and high-grade squamous intraepithelial lesions/CIN 2 or 3 occurred in 36 (9%) of the adolescents. No cases of invasive carcinoma were found. CONCLUSIONS: Among adolescents with ASC-US, the rate of squamous intraepithelial lesions/CIN is similar to that of adults. Although the optimal management of ASC-US in adolescents is unknown, these patients warrant close follow-up. LEVEL OF EVIDENCE: III     

Effective cervical neoplasia detection with a novel optical detection system: a randomized trial

OBJECTIVE: To assess whether the use of a novel optical detection system (ODS) as an adjunct to colposcopy increases the detection of biopsy-confirmed CIN 2,3. METHODS: This is a multicenter two-arm randomized trial comparing colposcopy alone with colposcopy plus a pre-commercial ODS system that utilizes fluorescence, white light tissue reflectance, and cervical video imaging. Patients were recruited from 13 colposcopy clinics in a variety of practice settings. 2299 women referred for the evaluation of an abnormal cervical cytology were randomized with stratification by cytology; subsequently 113 women were excluded for a variety of reasons. The main study outcomes were differences in true-positive rates (CIN 2,3 and cancer identified) and false-positive rates between the study arms. RESULTS: The true-positive (TP) rates were 14.4% vs. 11.4% (p=0.035, one-sided) for the combined colposcopy and ODS arm compared to colposcopy-only arm, respectively, in women with either an atypical squamous cell (ASC) or low-grade squamous intraepithelial lesion (LSIL) cytology result. TP rates were similar between the two arms among women referred for the evaluation of HSIL. The 26.5% gain in true-positives observed with the use of ODS and colposcopy among women referred for an ASC or LSIL cytology was achieved with only a fractional increase in number of biopsies obtained per patient (0.30) and a modest increase in false-positive rate (4%). In the combined colposcopy and ODS arm among women with ASC or LSIL, the PPV of biopsies indicated by ODS was 15.0% and the PPV of biopsies indicated by colposcopy was 15.2%. Joint hypothesis testing indicates that ODS and colposcopy provides benefit compared to colposcopy alone among women with ASC or LSIL. CONCLUSIONS: Combining ODS with colposcopy provides a clinically meaningful increase in the detection of CIN 2,3 in women referred for the evaluation of mildly abnormal cytology results.     

Human papilloma virus testing in patient follow-up post cone biopsy due to high-grade cervical intraepithelial neoplasia

OBJECTIVE: We evaluated the contribution of the human papilloma virus (HPV) load in planning follow-up and management of women post cone biopsy for high-grade cervical intraepithelial neoplasia (CIN2-3). METHODS: Ninety-six suitable women were followed-up by Pap smears: two consecutive abnormal smears dictated referral for colposcopy-directed biopsy. Before colposcopy, HPV tests determined high-risk HPV DNA type and load (Hybrid Capture System type I). Patients histologically diagnosed with CIN1 or CIN2-3 underwent repeat conization or hysterectomy for residual disease. HPV load was compared to cytology for the detection of residual disease. RESULTS: At follow-up, 20/89 (22.4%) studied women had positive cytology reports of either low- (n = 11) or high-grade (n = 9) squamous intraepithelial lesion (SIL). Colposcopic biopsies diagnosed 9 CIN1 and 8 CIN2-3 cases. Residual disease was corroborated in 16/17 (94.1%) women and the status was readjusted based on cone biopsy/hysterectomy: CIN2-3 in 9 and CIN1 in 7. The positive prediction values for CIN2-3 residual disease with high-grade SIL, CIN2-3 on colposcopic punch biopsy, and high HPV load were 89, 100, and 100%, respectively. For CIN1 residual disease with low-grade SIL, CIN1 on colposcopic punch biopsy, and low and borderline HPV load, they were 54.5, 77.7, and 100%. The HPV load was a more accurate predictor for CIN1 or CIN2-3 on the cervical specimen in cases with low-grade SIL or CIN1 on colposcopic biopsy. CONCLUSIONS: Evaluating HPV loads after a positive cytology report may assist in triaging women post conization biopsy for CIN2-3 to appropriate treatment. Its high positive predictive value, specificity, and sensitivity for CIN1 and CIN2-3 and supplementary information could be especially pertinent for clinical management of low-grade SIL cases.     

Management and outcome of cervical intraepithelial neoplasia lesions: a study of matched cases according to HIV status

OBJECTIVES: To assess whether adequate strategies are used for the management of cervical intraepithelial neoplasia (CIN) in HIV-positive patients. METHODS: Setting: Retrospective study in a HIV reference university hospital. Sixty-eight HIV-infected patients who had undergone a cervical biopsy between January 1995 and March 2002 were matched for CIN and age with HIV-negative patients. Outcome: Assess mean of treatment strategy. Assess mean of treatment failure by immediate follow-up PAP smear and recurrence rate by long-term follow-up smears. RESULTS: Both groups of patients received similar treatments for their cervical anomalies. HIV-positive women were two times more likely to have involved margins after conisation than HIV-negative women (P < 0.01). Globally, two thirds of HIV-negative patients had a first follow-up PAP smear that was normal, while this was the case in only one third of HIV-positive women. These proportions were also significantly different after conisation (P < 0.01). The same differences were also observed after sustained follow-up. HIV-infected women who showed a recurrence of dysplasia were more likely to have failed antiviral therapy (9/44) than those without any recurrence (7/12) (P < 0.01). CONCLUSIONS: Higher rates of recurrence were observed among HIV-infected women, indicating that CIN management is more difficult and may require adapted guidelines in HIV-positive patients. In HIV-infected patients, an association was found between the absence of recurrence and a viral response to antiviral therapy.     

Cervical cytology testing in teens

PURPOSE OF REVIEW: Although cervical cytology screening programs have dramatically decreased rates of invasive cancer in developed countries, most guidelines in the USA were overaggressive in their management of abnormal cytology in adolescents and young women. These management strategies resulted in costly over-treatment. The purpose of this article is to review the evidence for the new guidelines in cytology screening in youth. RECENT FINDINGS: Natural history studies of human papillomavirus (the cause of abnormal cytology and cervical cancer) suggest there is little risk of a significant pre-cancerous lesion going undetected within the first 3-5 years after the onset of sexual activity. The American Cancer Society now recommends that screening be initiated within 3 years of the onset of vaginal intercourse but no later than 21 years of age. The American Society for Colposcopy and Cervical Pathology allows for follow-up of low-grade squamous intra-epithelial lesions with repeat cytology or human papillomavirus DNA testing rather than immediate referral to colposcopy. SUMMARY: The new recommendations appear to be safe and will decrease the current over-referral and over-treatment of adolescents and young women with HPV infections.     

Cervical cancer screening by simple visual inspection after acetic acid

OBJECTIVE: To estimate the sensitivity and specificity of visual inspection using acetic acid as a primary screen for cervical intraepithelial neoplasia (CIN). METHODS: Visual inspection was done on 1997 women aged 35-45 years in a screening trial in rural China. Each women had colposcopy and at least five cervical biopsies (directed biopsy of lesions, one biopsy at 2, 4, 8, or 10 o'clock at the squamocolumnar junction in each normal quadrant, and an endocervical curettage). RESULTS: Forty-three women had biopsy-proven CIN II, 31 had CIN III, and 12 had invasive cancer. In two women only the endocervix was positive (one with CIN II and one with CIN III). Visual inspection yielded normal results in 1445 women (72%), low-grade intraepithelial neoplasia in 525 (26%), high-grade in 21 (1%), and cancer in six (0.3%). With abnormal visual inspection defined as low-grade intraepithelial neoplasia or worse, the sensitivity for detecting biopsy proven CIN II or worse was 71% (61 of 86, 95% confidence interval [CI] 60%, 80%); the specificity was 74% (1420 of 1911, 95% CI 72%, 76%); the sensitivity was 65% for smaller lesions (37 of 57, 95% CI 51%, 77%), and 89% for larger lesions (24 of 27, 95% CI 71%, 98%) (P =.03). CONCLUSION: The sensitivity of visual inspection equaled or exceeded reported rates for conventional cervical cytology. Visual inspection and colposcopy have similar specificity profiles for CIN II and greater. The benefit of an inexpensive point-of-care diagnosis and treatment algorithm will be a powerful incentive to pursue visual inspection for cervical cancer screening in developing countries.     

Follow-up by combined cytology and human papillomavirus testing for patients post-cone biopsy: results of a long-term follow-up

OBJECTIVE: The goal of this study was to evaluate the clinical implications of integrating human papillomavirus (HPV) testing into a long-term follow-up and management protocol for women postconization for high-grade cervical intraepithelial neoplasia (CIN2-3). METHODS: Sixty-seven women were followed-up by Pap smears and HPV type and load testing (mean follow-up, 63 months; range, 50-72). Patients with persistent abnormal cytology on two consecutive smears and those with positive HPV test results (whatever their cytologic findings) were referred for colposcopy-directed biopsy. Patients histologically diagnosed with CIN2-3 and those with high-load HPV (whatever their histologic findings) underwent repeat conization or hysterectomy for residual disease. RESULTS: At follow-up, 29 (43.2%) women had positive cytology or positive HPV results and were referred for colposcopy. Eleven (37.9%) had high-grade cervical intraepithelial neoplasia or high-load HPV results and were further treated by reconization/hysterectomy. The respective positive predictive values of high-load HPV and low-grade squamous intraepithelial lesions were 100 and 60% for any CIN and 90 and 15% for CIN2-3. Only five of nine cases with a final diagnosis of CIN2-3 were originally identified by cytology: the other four were detected only by parallel evaluation by HPV testing. High-load HPV results with normal cytology or low-grade lesions harbored an 80% risk for CIN2-3. CONCLUSIONS: Adding HPV load assessment to the follow-up protocol of women postconization due to CIN2-3 lesions could help detect high-grade residual disease among low-grade lesions and normal cytology cases while concomitantly and safely bestowing the advantage of lowering the rates of colposcopic referrals and surgical procedures.     

2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests

A group of 146 experts representing 29 organizations and professional societies met September 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. Recommendations for managing atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion (LSIL) are essentially unchanged. Changes were made for managing these conditions in adolescents for whom cytological follow-up for 2 years was approved. Recommendations for managing high-grade squamous intraepithelial lesion (HSIL) and atypical glandular cells (AGC) also underwent only minor modifications. More emphasis is placed on immediate screen-and-treat approaches for HSIL. Human papillomavirus (HPV) testing is incorporated into the management of AGC after their initial evaluation with colposcopy and endometrial sampling. The 2004 Interim Guidance for HPV testing as an adjunct to cervical cytology for screening in women 30 years of age and older was formally adopted with only very minor modifications.     

Colposcopy

Though in the 1980s, colposcopically-directed biopsy excluded over 90% of CIN 3 and cancer (CIN 3+), recent reviews found sensitivity of colposcopically-directed biopsy for CIN 3+ of 50-65%. Studies from China showed that the sensitivity of colposcopically-directed biopsy for CIN 3+ is higher for large CIN 3+ than for small CIN 3+ and higher for associated high-grade cervical cytology than for low-grade cervical cytology. Colposcopically-directed biopsy excluded over 90% of CIN 3+ in the 1980s because colposcopy clinics in the 1980s evaluated women with high-grade cytology that had large CIN 3+; it no longer excludes CIN 3+ well because current colposcopy clinics evaluate women with low-grade cytology that have small CIN 3+. When colposcopically-directed biopsy is used to exclude CIN 3+ our understanding of the natural history of CIN is skewed, errors occur in defining appropriate screening practice, and inaccurate diagnosis results in incorrect treatment. The impression that CIN is more common on the anterior lip of the cervix is an artifact introduced by the inaccuracy of colposcopy. An unjustified enthusiasm for screening with acetic acid aided visual inspection (VIA) occurred when the sensitivity of VIA for CIN 3+ was inflated by screening studies using colposcopically-directed biopsy as the gold-standard for CIN 3+. To limit the harm of inaccurate diagnosis associated with colposcopically-directed biopsy, at colposcopy we advise random biopsies at the squamocolumnar junction in cervical quadrants without visible lesions and, unless the woman is pregnant, endocervical curettage (ECC). As the diagnosis of CIN 3+ solely by ECC is uncommon in women under age 25, the ECC may be omitted in women under age 25 years. If multiple cervical biopsies are performed, to limit discomfort, a bronchoscopy biopsy instrument which obtains 2-mm biopsies should be used.     

Clinical and economic implications of adding HPV tests to the routine cytology follow-up and management of patients with histologically defined cervical intraepithelial neoplasia grade 1

OBJECTIVE: The objective of this study was to evaluate the clinical and economic implications of adding human papillomavirus (HPV) testing to the follow-up and management protocol of women with a histological diagnosis of low-grade cervical intraepithelial neoplasia (CIN1). METHODS: The study cohort consisted of 314 women with histological diagnosis of CIN1 and who met the inclusion criteria. They were followed-up by pap smears and samples for HPV tests that were obtained and analyzed on the first visit after referral. HPV assessment was carried out later. Colposcopy and biopsies were performed when there were two consecutive abnormal pap results or positive HPV tests. Women with any degree of CIN underwent cone biopsies. RESULTS: The positive predictive value (PPV) of low-grade squamous intraepithelial lesion and high-grade squamous epithelial lesion to identify high-grade lesions (CIN2-3) were 48.9 and 95%, respectively. The PPV of low-risk HPV type for CIN1 and that of high-risk HPV type for CIN2-3 were both 97%. Of the 314 study participants, 68 (21.6%) patients were positive for HPV analysis, and 67 of these (98.5%) had either CIN1 or CIN2-3 on the cone biopsy, with an overall PPV of 95%. The cost effectiveness ratio was $1457 per additional case detected by the "HPV approach." CONCLUSIONS: Testing for the presence of high-risk HPV types is both clinically and economically more beneficial than cytology in the follow-up and management of patients with a diagnosis of CIN 1 because of its better sensitivity, specificity, and PPV reports.     

Does Typing of Human Papillomavirus Assist in the Triage of Women with Repeated Low-Grade, Cervical Cytologic Abnormalities?

Objective.To evaluate the ability of testing for high-risk human papillomavirus (HPV) using the hybrid capture technique to detect cervical intraepithelial neoplasia (CIN) in patients with repeated low-grade cervical cytologic abnormalities and an adequate and normal colposcopy.Methods.Hybrid capture testing and LEETZ were performed on 166 women with repeated low-grade cervical cytologic abnormalities who were referred for colposcopy which was to be adequate and normal.Results.A highly significant correlation (P< 0.0001) was found between a positive test for high-risk HPV types and the finding of CIN II,III. In 67 women with atypical squamous cells of undetermined significance on repeated cytologic studies, a positive test for high-risk HPV types had a sensitivity and specificity of 90 and 96.5%, respectively, for detecting CIN II,III. In 99 patients with low-grade squamous intraepithelial lesions found on repeated cytologic study, a positive test for high-risk HPV types identified all patients as having CIN II,III on cone biopsy (sensitivity, 100%), with a specificity of 86.4%. Restriction of tissue sampling to women who were positive for high-risk HPV types would have reduced the number of tissue samplings performed to 20.4%, while identifying 20 of 21 patients with biopsy-confirmed CIN II,III.Conclusion.A positive hybrid capture test for high-risk HPV types is highly sensitive and specific for detecting CIN II,III in patients with repeated low-grade cervical cytologic abnormalities and an adequate and normal colposcopy and may be used in the triage of these women before performing tissue sampling.     

Cervical cancer screening of HIV-positive women: is a prolongation of the screening interval meaningful?

OBJECTIVE: Cervical cancer screening guidelines stated recently that the screening interval of healthy women can be extended up to 3 years. Can those recommendations be applied for high risk populations? MATERIAL AND METHODS: In a prospective setting 305 HIV-positive women have been enrolled in this analysis between September 2000 and December 2003. Patients have been characterized according to HPV (human papilloma virus) prevalence, CIN (cervical intraepithelial neoplasia) incidence and CD4 cell count. RESULTS: 41 % of all HIV-positive women were HPV positive (oncogene subtypes). In patients with diminished CD4 cells the HPV prevalence increased to 60 % (54/90). CIN was found in 27 % (83/305) women. CIN was more frequent by HPV-positive women with a CD4 cell count < 200 mm (3) (52 %, 38/72). The CIN incidence was also high in HIV-positive women with negative HPV infection and diminished CD4 cell count (39 %, 7/18 vs.7 %, 11/161). CONCLUSIONS: The current cervical cancer screening guidelines are not helpful in HIV-positive women. The CIN incidence is significantly higher as in the HIV-positive population. For this reason this high risk population as e. g. HIV-infected women need an intensive care of diagnostic tools and short screening intervals to detect CIN.     

Cervicography for triage of women with mildly abnormal cervical cytology results

OBJECTIVE: To estimate the sensitivity and specificity of cervicography in detecting cervical cancer precursor lesions in women participating in the National Cancer Institute's multicenter atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion triage study (ALTS). STUDY DESIGN: Cervigrams were obtained from 3134 women with a referral Papanicolaou smear diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. Cervigram and cervical histology results were compared by using cervical intraepithelial neoplasia (CIN) 2 and CIN 3 disease end points. RESULTS: Of 3134 women, 444 had histologic findings of more than or equal to CIN 2 and 222 had CIN 3. Cervicography interpretation by using a threshold of greater than or equal to atypical had a sensitivity, specificity, and positive and negative predictive values of 79.3%, 61.0%, 13.4%, and 97.5%, respectively, for detecting greater than or equal to CIN 3. Cervicography was more sensitive (80.8% vs 57.1%), but less specific (55.7% vs 81.8%), for detecting CIN 3 in women younger than 35 years compared with women 35 years or older, respectively. CONCLUSIONS: Cervicography functioned moderately well at detecting CIN 2 or CIN 3 in women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion Papanicolau smear results. Cervigram sensitivity was better for younger women.