Management of abnormal Papanicolaou smears: A review

Cytologic cervical screening has led to a dramatic reduction in the incidence of and death rates from cervical cancer. The new system of classification of Papanicolaou smears was introduced in 1991. The revised version of the Bethesda System combines human papillomavirus (HPV) and cervical intraepithelial neoplasia I/mild atypia into low-grade squamous intraepithelial lesion (LGSIL); and moderate dysplasia, severe dysplasia, and carcinoma in situ into high-grade squamous intraepithelial lesion. An additional classification, Atypical Squamous Cells of Undetermined Significance (ASCUS) has also been created. Controversy still persists regarding the evaluation and management of patients with atypical squamous cells of undetermined significance (ASCUS) and LGSIL. The majority of women with mild atypia on one Papanicolaou smear will have complete cytologic and colposcopic regression over a short interval. However, studies show that up to 16% of these lesions progress, and therefore diligent follow up is essential. The rate of colposcopically detected lesions that are more advanced than mild atypia is 10–30% in women with mild dysplasia on Papanicolaou smear. In the United Kingdom, a decision analysis model was used to determine whether mild dysplasia is best managed by colposcopy versus follow-up cytology. It was determined that the cost and mortality for the two methods are similar. Such analyses need to be carried out in the United States where the frequency of screening and of follow-up smears is higher. Current recommendations for the follow-up of ASCUS is by repeat cytology every 4–6 months for 2 years. Colposcopy is recommended for persistent ASCUS. According to current guidelines, LGSIL can be managed by immediate colposcopy or follow-up cytology. More studies are needed using the Bethesda system. Studies differentiating between ASCUS and LGSIL are needed to evaluate differences in malignant potential and management between these two cytologic abnormalities. Newer techniques, including HPV typing, cervicography, and computerized colposcopy, may help identify patients at risk for the development of cervical neoplasia.     

Contribution of human papillomavirus testing by hybrid capture in the triage of women with repeated abnormal pap smears before colposcopy referral

OBJECTIVE: The purpose of this work was to evaluate the ability of testing for high-risk human papillomavirus (HPV) types using the hybrid capture technique to predict the presence of cervical intraepithelial neoplasia (CIN) II,III in patients with repeated atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LGSIL) on Pap smears. METHODS: Hybrid capture testing and tissue biopsy were performed on 503 consecutive women with ASCUS or LGSIL on repeated Pap smears who were referred for colposcopy. RESULTS: A highly significant association (P < 0.0001) was found between a positive test for high-risk HPV types and CIN II,III, with an 87.0% positive predictive value and a 95.7% negative predictive value. In 226 women with ASCUS on repeated Pap smears, a positive test for high-risk HPV types had a 85.7% sensitivity and a 97% specificity for CIN II,III. In 277 patients with LGSIL on repeated Pap smears, a positive test for high-risk HPV types had an 88.2% sensitivity and a 94.7% specificity for CIN I,II. Reserving colposcopy examination for women who were positive for high-risk HPV types would have reduced the number of referrals for colposcopy to 24.6% and maintained a sensitivity of 87.0% for CIN II,III. CONCLUSIONS: A positive hybrid capture test for high-risk HPV types was highly sensitive and specific for the presence of CIN II,III in patients with ASCUS and LGSIL on repeated Pap smears. We believe that improved methodology will eventually enable more selective colposcopy referrals without affecting patient safety among these women.     

Poor correlation of high-grade cervical dysplasia with referral cytology: clinical implications

Objective: We questioned the diagnostic utility of cervical cytology by studying whether women with colposcopically guided biopsy proven high-grade cervical dysplasia or cancer had referral cytology results that correlated highly with their disease.Methods: All women with any cytologic abnormality or visible lower tract lesion(s) are referred for colposcopic examination. Ten thousand visits to our colposcopy clinic were prospectively collected, tracked, and reviewed, which revealed 566 cases of high-grade dysplasia and 8 cancers on biopsy. The proportion of high grade disease that was discovered by high grade cytology was measured.Results: The diagnosis of high grade cervical disease was not preceded by high-grade cytology (HGSIL) or “rule out cancer” cytology result (n = 95, 16.8%) in the majority of cases (P < .0001, χ²). High-grade disease was more often preceded by low-grade cytology (LGSIL) (n = 224, 39.5%), followed by atypical Papanicolaou smears (ASCUS) (n = 220, 38.9%) and visible cervical or vaginal lesion(s) (n = 27, 4.8%). A very high percentage of cancer cases had preceding HGSIL cytology (6 of 8 cases at least HGSIL, 75%).Conclusion: High-grade cervical neoplasia was more likely to be discovered following colposcopic triage of “minor” Papanicolaou smear abnormalities (ASCUS or LGSIL). The false negative rate of a single Papanicolaou smear to detect dysplasia may be as high as 65% (with specificity at the 90% range) (Fahey MT, Irwig L, Macaskill P. Meta analysis of Pap test accuracy. Am J Epidemiol 1995;141:7:680–9), making cytology an inaccurate diagnostic replacement for colposcopy. We should rethink the significance of minimally abnormal Papanicolaou smears when designing triage protocols that delay or eliminate colposcopy based on the Bethesda Grading System alone.     

Pap test results among low-income youth: prevalence of dysplasia and practice implications

OBJECTIVES: To describe Papanicolaou (Pap) test findings and identify prevalence and correlates of dysplastic cervical abnormalities in low-income adolescent females. DESIGN AND SETTING: This cross-sectional study included a modified random sample of female students ages 16 to 25 years at 54 U.S. Job Corps centers. PARTICIPANTS: 5,734 female students enrolled in a federal job training program. Admission health records were reviewed and abstracted. MAIN OUTCOME MEASURE: Pap test findings using the Bethesda classifications. Pap smear results indicating dysplasia (atypical squamous cells of undetermined significance [ASCUS] with dysplasia) or squamous intraepithelial lesions (low-grade squamous interepithelial lesions [LGSIL] or high-grade squamous intraepithelial lesions [HGSIL]). Participants with less severe findings were compared with those who needed follow-up. RESULTS: For 71.4% of participants, no abnormalities were found. 15.6% had benign cellular changes, 9.2% had reactive changes, and 9.9% had epithelial cell abnormalities. Of those tested, 5.6% (+/- 0.8%) had dysplastic Pap smear findings, with 0.3% (n = 12) HGSIL. All groups were equally affected, with abnormalities not associated with race/ethnicity, age, geographic region, education level, size of city of residence, or receiving public assistance. CONCLUSIONS: In this population, dysplastic Pap smear results were not uncommon. Findings indicate that Pap screening, alone or in combination with more sensitive tests, can identify cervical abnormalities, including HGSIL, that suggest a need for further evaluation or follow-up.     

Improved early detection of cervical intraepithelial lesions by combination of conventional Pap smear and speculoscopy

PURPOSE: To evaluate the efficacy of the addition of speculoscopy to a Pap smear in cervical cancer screening. METHODS: All women were screened using the Pap smear plus speculoscopy (PapSure) and colposcopy in the multicenter trial. The final diagnosis of each patient was based on a histological evaluation of the colposcopic target biopsy. Results were analyzed using a proportional compare test, sensitivity, specificity and predictive value with significant value determined at less than 0.05. RESULTS: Of 1,717 eligible cases, 26 cases had LGSIL and 16 cases had HGSIL. Of the Pap smears, five cases had LSIL and 14 cases had HGSIL. Of the combination of the PapSure, 23 cases had LGSIL and 16 cases had HGSIL. The sensitivity of the Pap smear to that of PapSure was calculated at 45.2% and 92.9%, respectively (p < 0.001). The estimated cost to detect a cervical lesion using PapSure is less than that of the Pap smear. CONCLUSION: The addition of speculoscopy along with a Pap smear screening results in early detection of cervical lesions in comparison to the Pap smear alone. This screening combination is also more cost-effective and requires fewer visits to the clinic in comparison to a Pap smear screening alone.     

Vulvar intraepithelial neoplasia in adolescents with abnormal Pap smear results: a series report

OBJECTIVE: The objective of this study was to determine the prevalence of vulvar intraepithelial neoplasia (VIN) in adolescents presenting for cervical colposcopy in an adolescent gynecology office. MATERIALS AND METHODS: We conducted a retrospective chart review from 1999 to 2002 of the concomitant diagnosis of cervical intraepithelial neoplasia and VIN in our private general pediatric and adolescent practice in patients younger than 22 years of age who underwent cervical colposcopy as well as evaluation of the vulva secondary to gross and microscopic visualized lesions. RESULTS: Sixty-one patients underwent colposcopy for abnormal Pap smears; we found a 10% overall prevalence of vulvar intraepithelial neoplasia. Forty-four percent (n=27) underwent concomitant evaluation of the vulva; from these, 22% (n=6) fulfilled the characteristics of vulvar and cervical intraepithelial neoplasia. CONCLUSION: In the presence of cervical cytology abnormalities, VIN may be more common than recognized and careful screening is definitely warranted.     

Loss to follow-up of cervical smears without endocervical columnar cells is not disturbing

OBJECTIVE: To investigate the six-month recommended follow-up after mass screening of Pap smears because of the absence of endocervical columnar cells (ECC-) or ECC+ smears with atypical squamous or glandular cells of undetermined origin (ASCUS/AGUS) or low-grade squamous or glandular intraepithelial lesions (LSIL/LGIL) in a Dutch mass screening cervical cancer programme. METHODS: Data were extracted from computerised medical records of national representative Dutch general practices. We have studied the attendance at and the outcome of the subsequent Pap smears after a 6-month recommendation. RESULTS: The six-month follow-up was linked to 8.7% of the Pap smears (n = 1,002); 77.6% were without endocervical columnar cells (ECC-). Clear differences were found between the follow-up of ECC+ and ECC- smears; after 36 weeks of follow-up of 43.5% the women had an ECC- smear and 66.9% had other conditions. For initial ECC- Pap smears, 84.1% had no abnormalities in the subsequent Pap smear; for initial ECC+ Pap smears, in about 64% of the cases no abnormalities were found (p < 0.0001). CONCLUSIONS: Repeating ECC- smears has a low follow-up rate but also lacks evidence-based necessity. However, for the other 6-month recommended Pap smears, one in five women had still not responded within one year, so improvement is necessary.     

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

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

Situation analysis of atypical squamous cells of undetermined significance smears in Songklanagarind Hospital

OBJECTIVE: To review the incidence, management, follow-up rate and colposcopic diagnosis of atypical squamous cells of undetermined significance (ASCUS) detected on cervical smears in Songklanagarind Hospital, Thailand. METHODS: A retrospective study of ASCUS smears taken during January 2000 to March 2001 at Songklanagarind Hospital was performed. The type of management was classified and the follow-up rate was detected. Cases with colposcopy, tissue biopsy, endocervical curettage, conization and hysterectomy specimen were reviewed. In the cases without tissue biopsy, the final diagnoses were based on the colposcopic examination. RESULTS: Among the 25068 Pap smears examined, the incidence of ASCUS was 0.62%. Of these, only 56.13% received the further evaluation. The non-compliance rate was 18.71%. The incidences of cervical intraepithelial neoplasia (CIN) and invasive cancer among the cases who received colposcopy were 15.96% and 2.13%, respectively. The incidence of CIN or invasive cancer in ASCUS favor reactive and ASCUS favor neoplasia were not different statistically significant. CONCLUSIONS: Management of ASCUS smears by follow-up may be inappropriate. A practice guideline which consists of active management, intensive follow-up system and well-organized data management should be used to improve the situation.     

Are There Flaws in the Follow-Up of Women With Low-Grade Cervical Dysplasia in Ontario?

BackgroundWhen cervical cytology screening shows atypical squamous cells of unknown significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL), and cervical cytology screening has not been performed in the previous year, it is recommended that cytology screening be repeated six months later. Women with persistent abnormalities should be referred for colposcopy. We explored provincial databases in Ontario to determine whether these recommendations were always followed.MethodsCervical cytology reports in Ontario are contained in a provincial database, deterministically linkable to other health services databases, including those recording physician reimbursement claims for colposcopy. We identified all women in Ontario who had a first time diagnosis of ASCUS or LSIL in 2008 or 2009. We searched for additional cytology reports and for colposcopy billing claims during the 24 months following the date of the first abnormal report. We assessed the interaction of socioeconomic status, having abnormal cytology, and having repeat cytology after a report of low-grade abnormal cervical cytology.ResultsA total of 74 770 women had a first time report of low-grade abnormal cytology. Among women with ASCUS and LSIL, 69.7% and 60.3%, respectively, underwent repeat cytology. Repeat cytology following ASCUS disclosed normal (68.2%), ASCUS (19.3%), LSIL (10.6%), and high-grade squamous intraepithelial lesion (1.4%); following LSIL, the corresponding percentages were 48.3%, 18.0%, 30.8%, and 2.6%. Of women with ASCUS, 16.2% went directly for colposcopy; 14.0% did not repeat cytology or go for colposcopy. Of women with LSIL, 26.4% went directly for colposcopy but 13.4% had no follow-up.ConclusionWe have demonstrated the potential for substantial improvement in cervical cytology six months after a finding of ASCUS and LSIL. We found that many women with ASCUS and LSIL had unnecessary referrals directly for colposcopy, and we identified a lack of follow-up for one sixth of women with low-grade abnormal cytology.     

Interpreting epithelial cell abnormalities detected during cervical smear screening--a cytohistologic approach

PURPOSE: To determine the underlying pathology and clinical significance of epithelial cell abnormalities (ECA) identified during cervical Papanicolaou (Pap) smear screening. MATERIAL AND METHODS: A total of 19,215 Pap smears stained by Papanicolaou stain were screened during a 36-month period. They were classified according to The Bethesda System (TBS) for cervical cytology screening and the results of ECA were compared with histology. The chi square test was applied to determine the significance and validity of high-grade lesions on cytology diagnosis. RESULT: 360 cases of ECA were identified. Mean age at presentation was 50.58 years. Cytohistologic correlation of ECA was possible in n = 249 (69.17%) of cases. Out of these, 18 cases were negative, six were inflammatory, three were benign, and 222 cases showed pathology ranging from mild dysplasia to invasive carcinoma. The chi square test showed a highly significant predictive value (p < 0.001) for high-grade lesions detected on Pap smears. CONCLUSION: Pap smear results of high-grade squamous intraepithelial lesions (HSIL) or invasive malignancy are highly reliable and the patient may be considered directly for therapeutic intervention. Of cytologically detected ASCUS cases 38.89% were diagnosed as CIN (1-3) on histology. Thus the management of these patients needs to be re-evaluated. Atypical glandular cells of undetermined significance (AGUS) detected in postmenopausal women signify an underlying pathology. These patients should be further investigated and followed to biopsy if necessary.     

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 three management strategies for patients with atypical squamous cells of undetermined significance, after six months delay: A three-year experience in an Iranian university hospital

Background: A Pap test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5–10% of women with ASCUS harbour serious cervical disease.
Methods: We screened 3619 women, who attended to Mirza Koochak Khan Hospital at Tehran University of Medical Sciences with Pap smears, of whom 100 returned with ASCUS. After six months, each subject underwent a standard cytology (conventional Pap smear), human papillomavirus (HPV) DNA testing (identifying high-risk HPV types with polymerase chain reaction) and colposcopy with multiple cervical biopsies.
Results: Mean age was 44.09 ± 8.6 years. The estimated prevalence of cervical intraepithelial neoplasia (CIN) II or higher was 4%. When histologically verified high-grade lesions (≥ CIN II) were observed, the relative sensitivity of HPV DNA testing was 100% compared with conventional Pap smear, which performed 75% versus 100% relative sensitivity, respectively, using cytological diagnosis high-grade squamous intraepithelial lesion, or low-grade squamous intraepithelial lesion (LSIL) as the cut-off. Negative and positive predictive values (NPV and PPV) of Pap test were 98.9% and 100%. The NPV and PPV of HPV DNA testing were 100%.
Conclusions: Although less complicated than colposcopy, the repeat Pap smear triage algorithm for ASCUS may underdiagnose some women with high-grade CIN, when compared with colposcopy. Considering the high sensitivity of HPV testing, it may be useful as an alternative to the current policy of six-month repeat cytology for women with ASCUS results.     

Cervical dysplasia in pregnancy: progression versus regression post-partum.

OBJECTIVE: To assess the natural history of cervical dysplasia during pregnancy and determine the rates for progression or regression post-partum by the severity of the lesion. METHOD: This was a retrospective study of 100 patients screened by PAP smear. Lesions were graded by colposcopy and biopsy, and followed post-partum. RESULTS: Lesions were graded as ASCUS, LGSIL, and HGSIL. The majority of lesions showed a tendency to regress post-partum (approximately 64%), a trend that was statistically significant (P < .003). A substantial minority (approximately 34%) showed no change in severity of the lesion. The tendency for lesions to progress in severity was very low (approximately 3%). No patient had microinvasive disease. Of patients who had CIS, persistence of this lesion post-partum was present in 67%. CONCLUSION: Patients with cervical dysplasia in pregnancy may be followed conservatively with colposcopy and biopsy.     

Clinical validation of high risk HPV DNA testing versus ThinPrep cytology for primary cervical cancer screening

Objective(s)To compare the validity of the high risk HPV DNA testing using the hybrid capture II technique (HC-II) to ThinPrep cytology for primary cervical cancer screening.DesignCross sectional pilot study.SettingDepartment of Obstetrics and Gynecology, Taiba Hospital, Sabah Al Salem, Kuwait.MethodsConsecutive 1923 cervical smear samples were taken for ThinPrep cytological screening and hr-HPV DNA testing using HC-II assay. Histological diagnoses were obtained from a total of 426 women who had positive results on screening and a group of women with negative screening and suspicious cervix underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment.Main outcome measuresSensitivity, specificity, positive predictive value and negative predictive value of screening methods.ResultsHPV was found positive in 15.5% of cases. 19/22 cases (86.4.1%) with a biopsy diagnosis of CIN2+ had a HC-II positive test. For CIN3, HC-II was positive in all cases (100%). Assuming a similar specificity level, the relative sensitivity of the HC-II test was higher when histologically confirmed high grade lesions (CIN2+ or CIN3+) were observed. HC-II test had the best sensitivity when defining cases as CIN2+ or CIN3+ (98.7% and 100%, respectively). When using the ASCUS+ cytological cutoff, the differences in CIN2+ and CIN3+ sensitivity between HC-II test and ThinPrep cytology were statistically not significant. Specificity of the ThinPrep cytology for any low and high grade histological lesions was clearly >95% when cytological diagnosis LSIL+ cutoff was used and nearly 100% when HSIL+ cutoff was used. All these specificity estimates were high compared with HC-II test. The specificity of the ThinPrep cytology decreased with about 10% when ASCUS+ was the cutoff. At cutoff ASCUS+, specificity of HC-II was comparable or only slightly lower than with ThinPrep ASCUS+ cytology with no statistically significant differences.ConclusionsThinPrep smears and hr-HPV DNA detection by HC-II performed very well with regard to identifying high grade lesions. HPV DNA testing is a promising new technology for cervical cancer prevention and can be used for primary screening in conjunction with cervical cytology for women aged 30 years and older.     

Cervicography as an adjunctive test to visual inspection with acetic acid in cervical cancer detection screening.

OBJECTIVE: Validate Digital Cervicography as adjunctive cervical cancer screening test to VIA and Cytology. METHOD: Women (1292) were submitted to both cytological and VIA tests to obtain a sample of 301 positive VIA cases (23.3%) which have had the Digital Cervicography (DC) taken and evaluated. Just cases considered positive by DC (149/301 cases--49.5%) and/or positive Pap smear tests were referred to colposcopy and biopsy whenever indicated. RESULTS: Cervical smear was positive in 5.4%, including LGSIL (4%), HGSIL (1%) and one case of invasive cancer (0.4%), and 1.6% of ASCUS or AGUS). DC identified 81 positive cases (74 LGSIL; 5 HGSIL; 2 cancers). The sensitivity of cytology was 14.8%, and the DC was 100%. Corresponding specificities were 95.4% and 69.1%, respectively. The NPV and PPV for DC were 100% and 54.4%. CONCLUSION: DC increases sensitivity, specificity and positive predictive value of VIA, becoming a valid adjunctive screening test for cervical cancer in low resource settings.     

Liquid phase cytology in the primary screening for cervical cancer: a multicenter study]

The aim of this six-centre, split-sample study was to compare ThinPrep fluid-based cytology to the conventional Papanicolaou smear. Six Cytopathology laboratories and 35 Gynaecologists participated. 5428 patients met the inclusion criteria. Each cervical sample was used first to prepare a conventional Pap smear, then the sampling device was rinsed into a PreservCyt vial, and a ThinPrep slide was made. Screening of slide pairs was blinded. On initial screening, 29% more ASCUS and 39% more low-grade squamous intraepithelial lesions (LSIL) and more severe lesions (LSIL+) were detected on the ThinPrep slides than on the conventional smears (p = 0.001). Independent and consensus review confirmed 145 LSIL + diagnoses; of these, 18% more had been detected initially on the ThinPrep slides than on the conventional smears (p = 0.041). The ThinPrep Pap Test is more accurate than the conventional Pap Test and has the potential to optimize the effectiveness of primary cervical cancer screening.     

Diagnosing human papillomavirus of the female lower genital tract: failure of the Pap smear as a sole screening test

Of 197 patients referred for colposcopy who underwent repeat Pap smears and colposcopic biopsies (when indicated), histologic evidence of human papillomavirus (HPV) infection involving the endocervix, cervix, or vagina or all three sites was documented in 109 biopsies. Sixty-six (61%) had normal Pap smears at the time of colposcopy. Despite a specificity of 92% for detecting HPV, the Pap smear demonstrated a low sensitivity (39%), with a positive and negative predictive test value of 88% and 50%, respectively. In patients with biopsies revealing HPV infection without associated dysplasia, false negative Pap smears were found most often in women with strictly vaginal HPV (74%) (P less than 0.05), followed by those with coexistent cervical and vaginal HPV (65%), and then by those with solely cervical HPV (51%). We question the use of the Pap smear for the detection of lower genital tract HPV, particularly in patients with only vaginal involvement, especially when the smear is repeated at the time of colposcopy. Benefits and disadvantages of other screening tests for HPV are discussed.