Diagnosis of cervical intraepithelial neoplasia and human papillomavirus infection: punch biopsy versus cervical smear

Summary In 102 patients referred to our colposcopy clinic because of one to three Papanicolaou smears indicating cervical intraepithelial neoplasia (CIN) and/or abnormal colposcopy, routine smears and colposcopically directed punch biopsies were taken simultaneously. For detection and typing of human papillomavirus (HPV)-DNA in situ hybridization was performed in all biopsies and in 46 of the cervical smears. In cases of dysplastic lesions the number of HPV 16/18 (40.5%) and 31/33 (42.9%) was markedly higher than HPV 6/11 (16.6%) infection rate. In cases where simultaneous in situ hybridization in biopsy specimen and cervical smears was performed 21.7% showed a HPV negative smear and a positive biopsy, in 6.5% the results were the other way round. In 34.9% of cases with CIN I and 9.5% of cases with CIN II verified by punch biopsy the cytological smear did not indicate dysplasia. Our data show that mild and moderate CIN lesions of the cervix as well as HPV infection are detected more frequently by a combination of cervical smear and colposcopically directed punch biopsy than by cervical smear alone.     

Managing atypical squamous cells of undetermined significance in Papanicolaou smears

OBJECTIVE: To assess strategies using repeated conventional Pap smear and human papillomavirus (HPV) DNA testing, alone or in combination, for identifying women with concomitant cervical intraepithelial neoplasia 2 and 3 (CIN 2/3) in women with atypical squamous cells of undetermined significance (ASCUS) in their Pap smears. STUDY DESIGN: A total of 360 women cytologically diagnosed with ASCUS were referred for colposcopy and underwent a repeat Pap smear, a biopsy when necessary and HPV testing using three different modes of detection of high-oncogenic-risk HPV types: 1, first-generation Hybrid Capture test (HC-1) (Digene Diagnostics, Gaithersburg, Maryland); 2, second-generation Hybrid Capture test (HC-2); and 3, polymerase chain reaction (PCR). RESULTS: Nineteen patients (5.3%) had histologic CIN 2/3. The sensitivity and specificity of the repeat Pap smear alone for the detection of CIN 2/3 were 73.7% and 62.9%, respectively, when referring all women with a repeat Pap smear using an ASCUS-positive threshold. The proportion of women referred for colposcopy was 39.0%. When HPV testing for high risk was used for identification of women with histologic CIN 2/3, sensitivity and specificity were, respectively, 68.4% and 85.9% for HC-1, 89.5% and 73.9% for HC-2 and 89.5% and 59.0% for PCR. The rate of referral for colposcopy of these three modes of HPV testing was 16.9%, 29.4% and 44.0%, respectively. The sensitivity and specificity for identification of women with concomitant CIN 2/3 using a combination of repeat cytology showing a low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion and/or a test positive for high-oncogenic-risk HPV group were, respectively, 94.7% and 73.2% when used in combination with HC-2. The referral rate of women for colposcopy of this combined strategy was 30.4%. CONCLUSION: As compared to the strategy using abnormal repeat Pap smear alone, those using high-risk HPV testing with Hybrid Capture showed statistically significantly higher specificities and lower proportions of women with ASCUS referred for colposcopy. In particular, a promising strategy would be to refer for colposcopy only women with repeat Pap smears showing squamous intraepithelial lesion and/or those positive for high-risk HPV detected by Hybrid Capture testing.     

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.     

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.     

Detection and typing of human papillomavirus infection affecting the cervix,vagina and vulva

Summary The sensitivity of human papillomavirus (HPV) detection was compared by colposcopy, histology and DNA hybridization among 304 women with abnormal Papanicolaou (Pap) smear. Colposcopically directed biopsies revealed HPV infection in 71% of cases, DNA hybridization in 35%, and both together in 78%. DNA hybridization detected HPV in 24% of the 84 benign cases with no histological signs of HPV, in 32% of the 133 condylomas verified by biopsies and in 51% of the 85 cases with intraepithelial neoplasia, 95% of which presented histological signs of HPV. The pattern of occurence of different HPV-types resembled findings in earlier reports. HPV infection is common with abnormal Pap smears and it can be identified relatively reliably by means of cytology, colposcopy and histology. DNA hybridization serves as a complementary technique which may reveal the oncological potential of the virus.     

Evaluation of the atypical Pap smear

Two hundred thirty-six consecutively referred patients with "atypical" but not dysplastic Pap smears were evaluated by colposcopy and directed biopsies to assess the significance of this ambiguous result. Additionally the histologic diagnosis was compared with the results obtained by repetition of the Pap smear, interpretation of cervigrams, and the visual impression of the coloposcopist to evaluate the accuracy of these three modalities as intermediate screening procedures. Fifty-eight patients (25%) had biopsy-proved cervical intraepithelial neoplasia. Repeat Pap smears identified only 17% of these patients. Colposcopists noted atypical transformation zones in 97% of the patients with cervical intraepithelial neoplasia. Cervigrams identified 81% of the cervical intraepithelial neoplastic lesions but had a 15% method failure (uninterpretable). The time-honored tradition of repeating atypical smears before definitive diagnostic procedures are performed is to be condemned. Neither colposcopy nor cervicography was judged to be an ideal intermediate screening procedure, but both were superior to Pap smear repetition.     

应用计算机辅助细胞检测系统检测子宫颈涂片中人乳头状瘤病毒感染

目的评价计算机辅助细胞检测（ｃｏｍｐｕｔｅｒａｓｉｓｔｅｄｃｙｔｏｌｏｇｉｃｔｅｓｔ,ＣＣＴ）系统检测宫颈涂片中人乳头状瘤病毒（ｈｕｍａｎｐａｐｉｌｏｍａｖｉｒｕｓ,ＨＰＶ）感染的敏感性与准确性。方法对１５８例外阴尖锐湿疣患者的子宫颈涂片,采用ＣＣＴ检测技术进行细胞病理学诊断,其诊断标准依据ＴｈｅＢｅｔｈｅｓｄａＳｙｓｔｅｍ（ＴＢＳ）分类法。同期行阴道镜指引下的子宫颈活组织检查和聚合酶链反应（ＰＣＲ）技术检测宫颈拭子中的ＨＰＶＤＮＡ。结果ＣＣＴ诊断宫颈ＨＰＶ感染的敏感性：与组织学检查对照,为７４６２％;与ＰＣＲ检测对照,为６９１１％。准确性：与组织学检查对照,为６７７２％;与ＰＣＲ检测对照,为７０８８％。结论ＣＣＴ作为一种细胞病理学检测技术,用于诊断宫颈ＨＰＶ感染或亚临床感染,有临床应用价值     

Visual inspection with acetic acid and cytology as screening methods for cervical lesions in Cameroon.

OBJECTIVES: To assess the accuracy of visual inspection with acetic acid (VIA) as a screening method for cervical lesions. METHODS: VIA and cytological smears were carried out on the cervices of non-pregnant women aged 30-60 years with no previous history of cervical cancer. Cervices with aceto white lesions or positive Pap smears, and one in ten negative cervices (control), were biopsied. RESULTS: 5010 women were enrolled, 4813 (96.1%) were screened. 4767 (99.%) had adequate cytology smears. 574 (11.9%) had colposcopy. 1743 biopsies were obtained of which 528 were controls. The sensitivity of VIA was 70.4% versus 47.7% for Pap smear. VIA specificity was 77.6% versus 94.2% for Pap smear; PPV for VIA was 44.0% versus 67.2% for Pap smear; and NPV for VIA was 91.3% versus 87.8% for Pap smear. CONCLUSIONS: VIA has acceptable test qualities and may in low resource settings be implemented as a large scale screening method.     

Management of the mildly abnormal Pap smear: a conservative approach

Follow-up and management of the mildly abnormal Pap smear has been the subject of controversy in the medical literature. At Fitzsimons Army Medical Center, patients with initial Pap smears reported as "inflammatory atypia" or mild dysplasia were treated with specific therapy for vaginitis and/or cervicitis. Follow-up smears were performed 6 to 8 weeks later. Of the above groups, 80 and 58%, respectively, were negative on repeat smear. A third group of patients with Pap smears reported as consistent with human papillomavirus (HPV) were not treated but had repeat smears performed at 6 to 8 weeks. Of these, 76.4% reverted to normal. The results of the colposcopically directed cervical biopsies obtained on patients with persistently abnormal smears are reported. These findings support a conservative plan for follow-up of mildly abnormal Pap smears.     

Evaluation of the risk of cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant patients receiving immunosuppressive therapy.

OBJECTIVE: To investigate the risk of cervical intraepithelial neoplasia and the coexistence of human papilloma virus (HPV) infection in renal transplant patients receiving immunosuppressive therapy. MATERIALS AND METHODS: Cervical Papanicolaou (Pap) smear and colposcopic examinations were performed in 48 renal transplant patients receiving immunosuppressive therapy. Microbiological and histopathologic findings were discussed. RESULTS: The patients were evaluated as to cervical neoplasia risk factors and the results were found to be statistically insignificant (p>0.05). Genital neoplasia was encountered in 20 of the 48 renal transplant patients. Koilocytosis developed in 6 out of 8 (75%) patients who were receiving high dose immunosuppressive therapy due to transplant rejection. HPV was found in 2 out of 48 patients; these 2 patients had koilocytosis in their cervical biopsies. The difference between the positive predictive value of colposcopic evaluation and the Pap smear was found to be insignificant (p>0.05). However, if colposcopy had not been performed in two cases of cervical intraepithelial neoplasia class I (CIN-I) and in one case of cervical microinvasive carcinoma, the cases would have been incorrectly diagnosed as normal by the false-negative results of the Pap smear. CONCLUSION: Renal transplant patients who were undergoing immunosuppressive therapy were found to be at increased risk of developing cervical intraepithelial neoplasia. All the patients using immunosuppressive agents should be followed-up by Pap smears every six months and by colposcopic evaluation every year. Avoiding high-risk sexual acts will decrease the risk of HPV transmission and the risk of genital neoplasia as well.     

A Study of Cervical Intraepithelial Neoplasia in Pregnancy

Objective

To find the incidence of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) in pregnant women and compare Pap smear with the HPV DNA test in detecting HPV infection.

Materials and Methods

Hundred antenatal women, irrespective of gestational age, were enrolled as subjects in this prospective pilot study for blood investigations, wet mount examination of cervical discharge, Pap smear, and high-risk HPV DNA detection of cervical scrape by PCR. Women showing abnormality in Pap smear and/or those who were high-risk HPV DNA positive were subjected to colposcopy.

Results

The incidence of HPV-positive pregnant women was 18 %. Koilocytosis on Pap smear was observed in six women. Three high-risk HPV DNA-positive women showed changes consistent with CIN 1 on colposcopy.

Conclusions

The HPV DNA test is the most sensitive and reliable in detecting HPV infection as compared to Pap smear, but considering the cost of PCR, Pap smear screening of all antenatal women was recommended.     

Clinical significance of hyperkeratosis and parakeratosis in otherwise negative Papanicolaou smears

To ascertain the clinical significance of hyperkeratosis and parakeratosis in otherwise negative Papanicolaou smears, we retrospectively reviewed 96 patients with these findings seen during a 32-month period. Evaluation included repeating the smear and performing colposcopy in all patients. Colposcopically directed biopsy and endocervical curettage were performed when appropriate. Only one patient had human papillomavirus (HPV) infection. The isolated finding of hyperkeratosis or parakeratosis was not associated with an increased incidence of cervical intraepithelial neoplasia or HPV and, clinically, was not associated with uterine descensus or vaginal prolapse.     

Prevalence of high-risk human papillomavirus (HR-HPV) types 16 and 18 in healthy women with cytologically negative Pap smear

OBJECTIVE: To study the prevalence of high-risk human papillomavirus (HR-HPV) types 16 and 18 in healthy women with negative Pap smears in identifying women with underlying cervical squamous intra-epithelial (SIL) lesions. METHODS: A total of 3300 women who were attending the Gynecology OPD of Lok Nayak Hospital, one of the major government tertiary hospitals in New Delhi, were screened during a 1-year study period, and 2079 (63%) of them were found to have cytologically negative Pap smear with inflammation and the rest (37%) also had negative Pap report but without inflammation. Hundred and sixty of these sexually active women aged between 20 and 60 years were randomly selected, and were investigated by colposcopy and a guided biopsy was done wherever required. HPV types 16 and 18 DNA was detected in scraped cervical cells from all women using type-specific primers in polymerase chain reaction (PCR). RESULTS: The high-risk HPV (type 16 and 18) prevalence by PCR was found to be 10% (16/160). Histopathological findings were obtained in 123 women, out of which 15 had LSIL and four had HSIL. High-risk HPV types 16/18 could be detected in nine out of these 19 (47.3%) squamous intra-epithelial lesions (p < 0.00008) which includes two out of the four women (50%) having HSIL, while only seven out of 104 (6.7%) of the subjects with normal (negative) Pap reports (p = 0.03) had infection of high-risk HPV. CONCLUSION: The results indicate that about 10% of women who show a negative Pap smear, but have inflammation are positive for high-risk HPV types 16/18 and about 15% harbor squamous intra-epithelial lesions. It is suggested that high-risk HPV detection can be utilized as an adjunct to routine cytology screening programs to identify 'high risk' women who have concurrently negative Pap smears but may harbor oncogenic HPV infection and/or more likely to develop CIN lesions.     

Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears

OBJECTIVE: To evaluate the association between high-risk human papillomavirus (HPV) DNA detection and histological diagnosis in women referred for atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) at Pap smear. METHODS: In this cross-sectional study, 146 women referred for AGC (124), AGC with high-grade squamous intraepithelial lesion (HSIL) (15), or AIS (7) were tested for HPV DNA using Hybrid Capture II (HC II). All women underwent colposcopic examination, and cervical biopsy was performed for 95 patients. Fifty-one women referred due to AGC with normal colposcopy and normal second Pap smear were scheduled for control visits every 4 months. RESULTS: The overall prevalence of HPV DNA was 38%. HPV DNA was detected in 93% of the women with HSIL associated with AGC and in 71% of women with AIS Pap smear, being significantly higher when compared with the prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had clinically significant histological lesions (CIN 2 or worse). High-risk HPV DNA was detected in only 16% of the women without significant abnormalities in biopsy, in contrast to 96% of those who had CIN 2 or CIN 3 and 75% of women with AIS. Eighty-five percent of women with invasive cervical carcinoma (squamous or adenocarcinoma) tested positive for HPV DNA. HPV DNA detection was significantly associated with histological diagnosis of CIN 2 or worse, with an odds ratio (OR) = 51.8 (95% CI 14.3-199.9). CONCLUSION: HPV DNA detection was strongly associated with the severity of cervical lesion (CIN 2 or worse) in women referred for AGC or AIS in their Pap smear. These data implicate the use of HPV testing in triage of women with AGC Pap smears.     

Prediction of cervical intraepithelial neoplasia grade 2-3 using risk assessment and human papillomavirus testing in women with atypia on papanicolaou smears

OBJECTIVE: To determine whether human papillomavirus (HPV) DNA testing and risk assessment can predict cervical intraepithelial neoplasia (CIN) 2-3 on biopsies in women with atypia on Papanicolaou smears. METHODS: One hundred ninety-five consenting women were referred for colposcopy because of atypia on Papanicolaou smears between September 1997 and April 1999. Before colposcopy, women completed risk assessments and had cervical swabs collected for HPV testing using the Hybrid Capture-II assay (Digene Corporation, Silver Spring, MD). Associations of demographic and clinical variables were assessed by chi(2) analysis, and logistic regression was used to assess factors associated with CIN 2-3. The cost-effectiveness of routine colposcopy versus reflex HPV testing by either conventional or liquid-based Papanicolaou smear media was compared. RESULTS: Cervical intraepithelial neoplasia was diagnosed in 70 of 195 women (35.9%), 55 (28.2%) with CIN 1 and 15 (7.7%) with CIN 2-3. High-risk HPV types were detected in 31.3% of all subjects, 36.4% of those with CIN 1, and 93.3% of those with CIN 2-3. By logistic regression, CIN 2-3 was associated only with detection of high-risk HPV (odds ratio 110.08, 95% confidence interval 8.35, 999. 00). The sensitivity of high-risk HPV for detecting CIN 2-3 was 93. 3%, specificity 73.9%, positive predictive value 23.0%, and negative predictive value 99.3%. The cost of reflex HPV testing using conventional smear or liquid-based media was less than routine colposcopy ($4809 and $4308, respectively, versus $4875 per case detected). CONCLUSIONS: Triage based on HPV testing would result in referral of approximately 31% of patients to colposcopy and appears to be a sensitive and cost-effective alternative to colposcopy.     

Role of the vaginal microbiological ecosystem and cytokine profile in the promotion of cervical dysplasia: a case-control study

OBJECTIVE: To identify alterations in the cytokine profile and microbial ecosystem of the vagina in association with cervical dysplasia. METHODS: Demographics, lifestyle variables and Papanicolau (Pap) smear results of subjects presenting to the same site for gynecologic complaints, obstetric visits or colposcopy were prospectively recorded. Vaginal smear for Gram stain, aerobic and anaerobic culture, pH, and wet mount and KOH examination for Trichomonas vaginalis, Gardnerella vaginalis and yeast organisms were performed. Vaginal lavage specimens were centrifuged, and the pellets and supernatants were assayed for human papillomavirus (HPV) by polymerase chain reaction and for cytokines interleukin (IL)-1beta IL-6, IL-10 and IL-12 by enzyme-linked immunosorbent assay (ELISA) respectively. Subjects with abnormal Pap smears underwent colposcopy and biopsy as indicated. RESULTS: Of 51 patients, 32 were referred for colposcopy, 12 presented with gynecologic needs, and seven presented for obstetric visits. Median age was 24 years. Demographics did not differ significantly between the dysplasia and control groups except for a trend towards more sexual partners in the dysplasia group. Biopsies were performed in 81% (26/32) of patients presenting for colposcopy and 17 revealed cervical intraepithelial neoplasia. IL-1beta, IL-6, IL-10, and IL-12 levels were elevated in 63% (20/32), 38% (15/39), 4% (2/49), and 0% of samples respectively. Elevated vaginal lavage IL-1beta was associated with a 6.1 odds ratio (95% confidence interval 1.06-35) of cervical dysplasia. Alterations in other variables studied were not associated with cervical dysplasia. CONCLUSIONS: Elevated IL-1beta, possibly representing a complex host inflammatory response to multiple pathogens, was demonstrated in patients with cervical dysplasia.     

Endocervical curettage in evaluating abnormal cervical cytology

OBJECTIVE: To determine the role of endocervical curettage (ECC) in the evaluation of women with abnormal cervical cytology and following treatment for cervical intraepithelial neoplasia. STUDY DESIGN: A retrospective chart review using the records of 2,126 patients who were seen at the Colposcopy Clinic, Baylor College of Medicine, between 1980 and 1995. All patients were referred because of an abnormal cervical smear and underwent repeat Pap smear, colposcopic examination in each case with biopsies as indicated, endocervical curettage and treatment, consisting of either cryotherapy, laser vaporization or a LOOP electrosurgical excision procedure. Following treatment, Pap smears were performed on a scheduled basis, and ECC was performed annually. RESULTS: The ECC was negative in 1,849 (87%) of the women. It was abnormal in 33% of women with unsatisfactory colposcopy and 10% of women with satisfactory colposcopy. ECC was abnormal in 21% of patients with a negative biopsy result and 42% of patients who did not have a biopsy performed. There was a significant increase in abnormal ECC results with increasing age. ECC had a high positive predictive value for ectocervical disease (86%) and a high negative predictive value for endocervical disease (90%). One year following treatment, < 4% of patients with a negative cervical smear had a high grade lesion detected on ECC. CONCLUSION: The use of ECC is helpful in detecting disease missed by routine colposcopy and biopsy and is most likely to detect ectocervical disease rather than true endocervical disease. Following treatment, ECC does not appear to be significantly more reliable than the Pap smear in detecting the presence of significant residual disease.     

Value of repeat cytology at the time of colposcopy for the evaluation of cervical intraepithelial neoplasia on Papanicolaou smears

The significance of repeat cervical cytology was evaluated in patients referred for colposcopy because of previous cervical intraepithelial neoplasia (CIN) 1 on cytologic smears. Between Jan 1, 1984, and Dec 31, 1986, 273 such patients were seen. The results of the repeat smears obtained prior to colposcopy were compared with those of colposcopically directed biopsies and of follow-up. The repeat smear was negative in 99 patients; it disclosed squamous atypia in 84, CIN 1 in 64 and CIN 2 or 3 in 26. Thirty-two patients whose repeat smear was negative had biopsy-documented CIN 1-3. Of the 84 patients with squamous atypia, 37 (44%) had biopsy-documented CIN 1-3. Thus, second smears in this group failed to disclose precancerous lesions in at least 69 patients. Of the 90 patients whose repeat smear were interpreted as showing CIN, 64, or 71%, had biopsy-documented CIN 1-3. Patients with a repeat smear showing CIN 1 or greater and normal colposcopy or a negative cervical biopsy must be followed closely: 33% of our study group (6 of 18) were found to have CIN later.     

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.     

Screening of premalignant cervical lesions for HPV 16 DNA by sandwich and in situ hybridization techniques

A series of 97 cervical smears and 69 directed punch biopsies derived from 84 consecutive women prospectively followed-up for cervical HPV (human papillomavirus) infections were studied using the sandwich hybridization and in situ hybridization techniques with HPV 16 DNA probes. The aim was to test the sensitivity and applicability of these two techniques in routine diagnosis of cervical HPV infections from smears. As a measure of specimen adequacy, the number of cells recovered in the cervical scrape was determined along with HPV 16 DNA in the sandwich hybridization test using human pro-alpha 2(I)-collagen gene probe. CIN (cervical intraepithelial neoplasia) was suggested in 56% of the patients by the Pap smear, and disclosed in 65% of the biopsies. HPV 16 DNA was present in 57% of cervical scrapes consistent with CIN, i.e., were of Pap smear classes III or IV. Forty percent of the scrapes not suggestive of CIN, i.e., Pap smear classes I or II, also contained HPV 16 DNA. The detection rate for HPV 16 DNA of the sandwich hybridization method was 89% of that of the in situ method in adequate scrapes, but only 43% in cell-poor specimens. The number of HPV 16 DNA-positive scrapes as compared with the total number of diagnoses obtained by studying also the biopsies was 31/36 (69 patients). The results indicate that the cervical scrape as a noninvasive specimen is applicable for screening of cervical HPV infections, and it can be studied with acceptable sensitivity by the rapid sandwich hybridization technique. However, if a punch biopsy is indicated it should be studied using the in situ hybridization technique that allows more sensitive detection of HPV DNA than any other hybridization method and enables the analysis of several HPV types in the same sample instead of only one HPV type in the scrapes.