Different Detectability of High-Risk HPV in Smears from Incident and Prevalent High-Grade Squamous Intraepithelial Lesions of the Cervix

Human papillomavirus (HPV) status in cervical smears from cervical intraepithelial neoplasia (CIN) 2/3 diagnosed in 36 of 892 women with a history of normal cytology and colposcopy (incident CIN 2/3) was compared with CIN 2/3 in 40 patients with a history of abnormal cytology (prevalent CIN 2/3). In all patients cervical smears for HPV testing and cytology and two cervigrams were taken. The scrapes were collected in hybrid capture assay solution and analyzed with the hybrid capture and general primer/type-specific primer polymerase chain reaction system (GP/TS-PCR) after DNA extraction. Patients with incident and prevalent CIN 2/3 were similar with respect to age. By GP/TS-PCR carried out under suboptimal conditions due to DNA extraction, HPV DNA was detected in 69.4% (25 of 36) of smears from incident CIN 2/3 compared to 95% (38 of 40) in prevalent CIN 2/3 (P= 0.003). Using hybrid capture, smears of incident CIN 2/3 were HPV positive in 50% (18 of 36) compared to 80% (32 of 40) in prevalent CIN 2/3 (P= 0.006). High-risk HPVs were significantly less common in smears from incident CIN 2/3 compared with prevalent CIN 2/3: 36.1% vs 72.5% by GP/TS-PCR (P= 0.001) and 47.2% vs 80% by hybrid capture assay (P= 0.003), respectively. Virus load in HPV-positive smears of prevalent CIN 2/3 was significantly higher than of incident CIN 2/3 using semiquantitative PCR (P= 0.0005). Thus, high-risk HPV types were detected less frequently and in lower concentration in smears from incident CIN 2/3 than in smears from prevalent CIN 2/3.     

Human Papillomavirus Testing in Primary Screening for Cervical Cancer of Human Immunodeficiency Virus-Infected Women, 1990–1998

Objective. Women infected with the human immunodeficiency virus (HIV) have an increased risk of cervical neoplasia while the value of cytologic screening is limited due to a high prevalence of inflammatory disease. The study was conducted to determine whether testing for human papillomavirus (HPV) DNA could improve primary screening for cervical cancer of these patients.Methods. One hundred thirty-eight HIV-infected women were examined between 1990 and 1998. Ninety-four patients with a total of 279 women-years were eligible for incidence evaluation. Colposcopy, cytology, and HPV DNA testing with the hybrid capture I assay were performed at each visit.Results. Seventeen cases of high-grade cervical neoplasia were diagnosed at study entry and 13 developed CIN II or CIN III during follow-up. The hybrid capture I assay detected 94.1% of prevalent and 100% of incident high-grade neoplasia, while the corresponding sensitivity of Pap smears using CIN I or worse as the referral criteria was 82.3% for prevalent and 69.2% for incident high-grade neoplasia. Eleven of 13 patients who progressed to histologically confirmed CIN II/III tested positive for HPV DNA at study entry compared with 5/13 women presenting with any degree of cytologic atypia at recruitment. The Pap smears of 36/94 women remained normal throughout the study while 54/94 patients remained negative for high-risk HPV types.Conclusion. Hybrid capture I identified high-grade cervical neoplasia more accurately than the Pap smear and appeared to be beneficial for primary cervical cancer screening in HIV-infected women.     

Correlation of human papillomavirus and adeno-associated virus 2 infection in cytology with Korean women

The purpose of our prospective study was to investigate the prevalence of adeno-associated virus (AAV) and human papillomavirus (HPV) 16 and/or HPV 18 infection in Korean women with normal cervical smears and those with HPV-associated cervical intraepithelial neoplasia (CIN) and cancer in cytobrush samples, and to evaluate the correlation between AAV 2 and HPV 16 and/or HPV 18 infection. AAV 2 was detected in CIN I (9.7%), CIN II (20%), CIN III (22.8%), and cancer (10%). HPV 16 was detected in CIN I (42%), CIN II (55%), CIN III (54.3%), and cancer (70%). HPV 18 was detected in CIN I (51.6%), CIN II (50%), CIN III (62.8%), and cancer (43.3%). HPV 16 or HPV 18 was detected in CIN I (18.3%), CIN II (80%), CIN III (71.4%), and cancer (80%). In normal and HPV-infected group, AAV 2 DNA was detected in 16.3% and 4.4% of samples, respectively. HPV 16 was detected in 10.2% of normal patients and in 44.4% of HPV-infected patients, and HPV 18 was detected in 12.2% of normal patients and in 40% of HPV-infected patients. HPV 16 or HPV 18 was detected in 18.3% of normal patients and in 57.7% of HPV infection. The correlation between AAV 2 and HPV 16 was statistically significant in normal and CIN I/II group only, and AAV 2 and HPV 16 and/or HPV 18 showed no correlation. Therefore, the correlation between AAV and HPV were not statistically significant. These data support the previous reports that AAV might not be associated with cervical tumorigenesis.     

Human papilloma virus in uterine cervix: a comparison of detection by morphology and by dot-blot hybridization.

Colposcopically directed cervical biopsies, smears, and swabs obtained from 210 women with a previous abnormal cervical cytology were evaluated for the presence of human papilloma virus (HPV) using morphology and dot-blot hybridization. The diagnosis of HPV infection in biopsies and smears examined morphologically was rendered using established criteria for condyloma/cervical intraepithelial neoplasia (CIN). In hybridization studies, DNA was isolated from cells obtained from cervical swabs and annealed with probes that detected HPV types 6/11, 16/18, and 31/33/35 using a dot-blot procedure. Ninety-five cases demonstrated morphologic evidence of condyloma/CIN; 51 of these (54%) were positive for HPV DNA (five cases 6/11, 21 cases 6/18, 20 cases 31/33/35, and five cases two different probes). HPV DNA was also detected in 6 of the 115 cases (5.2%) that were morphologically negative (three cases 16/18, three cases 31/33/35). The results demonstrated that morphology was more sensitive than dot-blot hybridization for detection of HPV-related lesions. The dot-blot hybridization did detect HPV DNA in a small percentage of the cases that showed no morphologic abnormality and was useful for typing of the HPV. At this juncture, however, the clinical significance of the latter findings is unclear.     

Dominant human papillomavirus 16 infection in cervical neoplasia in young Japanese women; study of 881 outpatients

OBJECTIVE: Human papillomavirus (HPV) infection is reported to be related to carcinogenesis in the uterine cervix. In Japan, screening for cervical cancer by cytology is performed in women over 30 years old. The purpose of this study was to determine whether there is an association between patient age and cervical neoplasia or HPV infection in Japanese women. METHODS: Specimens from 881 randomly selected patients who came to our clinic were tested for HPV DNA by using Hybrid Capture II, whereas specimens from a 204-patient randomly selected subset diagnosed with cervical neoplasia were tested for HPV DNA by using polymerase chain reaction (PCR). HPV typing was performed in all the PCR-positive cases. RESULTS: The HPV-positive rate in the 20- to 29-year-old patients (29.0% in the normal cytology/histology group and 85.5% in the abnormal group) was higher than in the 30- to 59-year-old patients, and the rate declined until age 60 when age increased. While HPV 18, HPV 52, other HPV types, and HPV types as a whole were frequently detected in 30- to 49-year-old patients, HPV 16 was detected more frequently in the younger group than the other HPV types (P = 0.03). Among the HPV 16-positive patients with cervical neoplasia, the proportion of cervical intraepithelial neoplasia (CIN) 3 cases was high (44%) in the 20- to 29-year-old group. CONCLUSIONS: Screening for cervical neoplasia by cytology should also be performed in women under 30 years old in Japan. The HPV typing could be a tool to strictly follow-up younger women who were diagnosed with CIN.     

Atypical squamous cells. A case-series study of the association between papanicolaou smear results and human papillomavirus DNA genotype.

Thirty women with "atypical" squamous cells but not cervical intraepithelial neoplasia (CIN) on their Papanicolaou smears were tested for the presence of human papillomavirus (HPV) with the Southern blot hybridization technique. The Papanicolaou smears were reviewed for the presence of atypical squamous cells according to Patten's criteria. Comparison groups consisted of 30 patients with normal, 29 patients with CIN I and 24 patients with CIN II Papanicolaou smears. Ten of the 30 women (33%) with atypical cells on Papanicolaou smears were positive for HPV DNA as compared to 17% with normal and 59% with CIN I or II Papanicolaou smears. HPV 16 was present in 70-80% of the HPV DNA-positive patients in each Papanicolaou smear group. Concurrent CIN was also identified on colposcopically directed biopsies in 27% of the patients with squamous atypia. Patients with atypical squamous cells on Papanicolaou smears had coexisting HPV infection and CIN in about one-third of the cases. Colposcopy and further follow-up are recommended for such patients.     

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.     

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.     

Efficacy of imiquimod 5% cream for persistent human papillomavirus in genital intraepithelial neoplasm

ObjectiveTo assess the clinical response to imiquimod 5% cream in patients with persistent human papillomavirus (HPV) infection after treatment of genital intraepithelial neoplasia.Materials and MethodsImiquimod 5% cream was applied to treat 76 women with persistent HPV after surgical therapy for cervical or vaginal intraepithelial neoplasia (CIN or VAIN). One sachet of cream was placed in the cervical os and vagina with an applicator twice weekly for 8 weeks. Repeated HPV evaluation and Papanicolaou (Pap) smear and/or biopsy were performed 3 months following treatment completion.ResultsIn total, 58 of the 76 patients (76.3%) were clear of HPV infection and had normal Pap smears after administration of imiquimod cream. Although atypia or mild dysplasia was noted in 15 of the 18 patients (83.3%) with persistent HPV infection after imiquimod cream treatment, the degree of severity was noticeably less than the initial diagnosis in most of these patients. Persistent HPV positivity was observed in 12 of the 64 patients (18.8%) with CIN and 6 of the 12 patients (50.0%) with VAIN.ConclusionTopical imiquimod 5% cream may be beneficial in most cases of genital intraepithelial neoplasia, especially CIN, with persistent HPV following surgical treatment.     

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.     

Triage of atypical squamous cells of undetermined significance with hybrid capture II: colposcopy and histologic human papillomavirus correlation

OBJECTIVE: To estimate the effectiveness of Hybrid Capture II to predict high-grade cervical intraepithelial neoplasia (CIN) from a cytological cervical sample. Evidence of high-risk human papillomavirus (HPV) was also determined from biopsy samples using the polymerase chain reaction (PCR) for women referred with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou smears. METHODS: We screened 8170 women with Papanicolaou smears, of whom 278 (3.4%) returned ASCUS. All ASCUS cases underwent colposcopy and Hybrid Capture II testing. High-grade CIN biopsy specimens were tested for high-risk HPV by PCR. RESULTS: Nearly 30% of ASCUS cases had CIN biopsy results (11.9% showing CIN II or CIN III and 17.6% showing CIN I). Hybrid Capture II positive rates were 93.3% for cases with CIN III, 72.2% for CIN II, and 51.0% for CIN I (P <.001). ASCUS-Premalignant Process Favored cases showed a 28.1% high-grade biopsy rate and a 100% Hybrid Capture II positive rate. For ASCUS-Undefined and ASCUS-Reactive Process Favored cases, Hybrid Capture II returned positive in 90.9% of CIN III and 61.5% of CIN II cases (P <.001). Sixty-nine of 178 (38.8%) patients with no evidence of CIN tested positive for Hybrid Capture II. Human papillomavirus deoxyribonucleic acid (DNA) high-risk subtypes were detected by PCR in the tissue of all high-grade CIN cases with negative Hybrid Capture II results. CONCLUSION: Hybrid Capture II returned negative in 25% of cases with biopsy-proven high-grade CIN with associated high-risk HPV DNA by PCR (non-Premalignant ASCUS subset), and positive in 39.3% of cases with normal results; this limits its clinical utility.     

宫颈癌及上皮内瘤变人乳头瘤病毒基因型的检测

目的:了解宫颈癌及上皮内瘤变人乳头瘤病毒(HPV)的感染率及其基因型的分布。方法:用PCR-RFLP法检测239例宫颈癌及上皮内瘤变患者HPV感染并进行分型。先用PGMY09/11共同引物扩增生殖道粘膜型HPV L1区的高度保守区,然后联合使用RsaⅠ、MseⅠ、PstⅠ和HaeⅢ4个限制性内切酶对阳性PCR产物进行酶切,利用不同的酶切片段鉴定HPV的基因型。结果:在239例宫颈癌及上皮内瘤变患者中共检出205例(85·8%)HPV感染,其中宫颈上皮内瘤变Ⅰ级(CINⅠ)、宫颈上皮内瘤变Ⅱ~Ⅲ级(CINⅡ~Ⅲ)和宫颈癌中HPV感染率分别是66·7%,89·9%和98·3%,差异有统计学意义(P<0·001)。在宫颈癌及上皮内瘤变中共检出22型HPV,其中主要基因型及其感染率分别是HPV16(45·6%)、58(12·1%)和52(6·3%)。结论:宫颈癌及上皮内瘤变中HPV感染的基因型至少可达22型,其中以HPV16、58和52为最常见。     

The relationship between human papillomavirus infection and cervical intraepithelial neoplasia in Turkish women

To compare the prevalence of cervical human papillomavirus (HPV) infection in Turkish women with normal Papanicolaou (Pap) smear and cervical intraepithelial neoplasia (CIN). In between March 2002 and November 2005, the study was designed as case-control study. Cytologic abnormalities in Pap smears were classified according to the Bethesda System (2001). Identification of the presence of HPV was carried out by the Hybrid Capture II test for all patients. To compare the groups, Chi-square test was used. A total of 1353 reproductive aged women were screened. Of them, 1344 (99.3%) had normal or class I Pap smear. Remaining nine cases (0.7%) had CIN at several degrees (five CIN I, three CIN II, and one carcinoma in situ). While all these nine cases with cervical pathologies had HPV, only 20 cases from the other group (1.5%) had HPV (chi(2) 466.1; P = 0.0001). This is the first study of the evaluation of the association between HPV and preinvasive cervical lesions in Turkish population. In spite of low general frequency (2.1%) of cervical HPV colonization in this population, a strong correlation was found between HPV and CIN.     

Human papillomavirus screening for women with atypical Papanicolaou smears.

A study was undertaken to evaluate the utility of human papillomavirus (HPV) DNA screening and colposcopy in the management of women whose Papanicolaou smears demonstrated atypia less than dysplasia. Fifty patients whose initial Papanicolaou smears were interpreted as showing atypia less than dysplasia were evaluated for the presence of HPV 16 DNA in exfoliated cervicovaginal cells and for histologic findings on biopsy. Those 50 patients were compared to two groups of patients: one consisting of 124 patients with biopsy-documented cervical intraepithelial neoplasia (CIN) and another of 112 patients with normal Papanicolaou smears. The presence of HPV 16 DNA was confirmed with Southern analysis in 46% of patients with atypical Papanicolaou smears, 46% with confirmed CIN and 11.6% with normal Papanicolaou smears. The 50 patients with atypical smears underwent colposcopically directed cervical biopsies, revealing the following results: 14 (28%) had normal histology, 29 (58%) had koilocytosis without dysplasia, and 7 (14%) had CIN. HPV 16 DNA was present in exfoliated cervicovaginal cells from a large percentage of patients from each category (50% of patients with normal histology, 41.2% with koilocytosis and 57% with CIN). HPV 16 DNA screening did not predict which patients with atypical smears had underlying CIN. Colposcopically directed biopsy remains the evaluation method of choice.     

Human papillomavirus typing in HIV-positive women

OBJECTIVE: Human papillomavirus (HPV) is the major cause of cervical carcinoma and cervical intraepithelial neoplasia worldwide. Certain HPV types have a strong association with and probably a causative role in the pathogenesis of premalignant cervical lesions. Epidemiologic studies in women infected by the human immunodeficiency virus (HIV) have shown an increased incidence of squamous intraepithelial lesions (SILs), which were predominantly high-grade. Six to 30 per cent of women diagnosed with atypical squamous cells of undetermined significance (ASCUS) on a Papanicolaou (Pap) smear harbor SIL in normal screening populations. This study was undertaken to determine the presence of low-and high-risk HPV types in women infected by HIV and to correlate the results to those of the Pap smear. STUDY DESIGN: HPV DNA typing (low- and high-risk) by Digene (Digene Corporation, Gathesburg, MD) hybrid capture methodology was performed on cervical swabs from 209 HIV-positive women. The results of HPV typing were correlated with those of the Pap smear in a retrospective analysis. RESULTS: One hundred and one women (48%) tested positive for HPV subtypes by DNA typing by the hybrid capture method. Of these, 64 patients (63%) had Pap smears which were read as being normal, having benign cellular changes, or having ASCUS (favor reactive process). Of these, 19 patients tested positive for both high-risk and low-risk subtypes, 32 patients tested positive only for high-risk subtypes, and 13 patients tested positive only for low-risk subtypes. CONCLUSION: HPV subtyping identifies a significant group of HIV-positive women who are at risk for developing cervical intraepithelial neoplasia, although they may not show significant abnormalities on their Pap smears.     

High-risk HPV DNA detection by Hybrid Capture II. An adjunctive test for mildly abnormal cytologic smears in women > or = 50 years of age

OBJECTIVE: To determine whether high-risk human papillomavirus (HPV) DNA testing could improve the detection of cervical intraepithelial neoplasia (CIN) and cancer in older women (> or = 50 years old) with mildly abnormal results on conventional cytology. STUDY DESIGN: The study was based on 119 patients aged over 50 (median, 62; range, 50-78) referred for colposcopy with Pap smears reported as atypical squamous cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesion (LSIL) from February 1997 to September 1998. The presence of high-risk HPV DNA (including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) was determined with the Hybrid Capture II (Digene, Inc., Silver Spring, Maryland) microplate method. Cytologic examination by Pap smear was based on the Bethesda System and, cervical biopsy was done via colposcopy. RESULTS: High-risk HPV DNA was demonstrated in 75.6% (34/45) of patients with LSIL and 52.7% (39/74) with ASCUS. Those who were HPV positive were significantly more likely to have CIN or cancer (odds ratio, 33.40; 95% confidence interval, 11.89-93.97; P < .0001). The sensitivity of HPV assay for detection of lesions more severe than CIN 2 was 100%, specificity 64.8%, positive predictive value 66.7% and negative predictive value 100%. CONCLUSION: The addition of a high-risk HPV DNA assay to cytologic examination appears to provide excellent sensitivity and negative predictive value for early detection of high grade CIN or cancer in older women with minimally abnormal Pap smears.     

Prevalence, Risk Factors, and Accuracy of Cytologic Screening for Cervical Intraepithelial Neoplasia in Women with the Human Immunodeficiency Virus

Objectives.The objective was to evaluate the sensitivity and specificity of cervical cytology in women infected with the human immunodeficiency virus (HIV), risk factors for abnormal cytology in HIV-infected and uninfected women, and risk factors for histologic diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-infected women.Methods.Methods included a cross-sectional analysis of cervical cytology, colposcopic impression, and histology in 248 HIV-infected women and multivariate analyses of risk factors for abnormal cytology in 253 HIV-infected and 220 uninfected women and risk factors for CIN in 186 HIV-infected women.Results.The sensitivity and specificity of cytology for all CIN grades were 0.60 and 0.80 and, for high-grade CIN, 0.83 and 0.74. The prevalence of abnormal cytology was 32.9% in HIV-infected and 7.6% in HIV-negative women. Independent risk factors for abnormal cytology were immunodeficiency [odds ratio (OR) 8–17,P< 0.001] and human papillomavirus (HPV) infection (OR = 5,P< 0.001). The prevalence of CIN on histology was 32% in HIV-infected women, and the only independent risk factor for CIN was oncogenic HPV type (OR = 5,P= 0.005).Conclusion.Given the high prevalence of abnormal cytology and CIN in HIV-infected women, cytologic screening has significant limitations. Both immunodeficiency and type of HPV infection are important risk factors.     

Human papillomavirus in women. A three-year experience in a county hospital colposcopy clinic.

The human papillomavirus (HPV) has been associated with cervical dysplasia and carcinoma. This report summarizes the authors' experience with HPV-related problems over three years, 1987-89, while managing 1,644 women at a county hospital colposcopy clinic. Probes for HPV DNA were not used, and the diagnoses were made with cytologic and histologic criteria alone. The percentage of patients referred to the clinic with HPV found on routine Papanicolaou smears rose significantly, from 3 in 1987 to 18 in 1989. Fifteen percent of those referred because of HPV on a Papanicolaou smear were found to have cervical intraepithelial neoplasia (CIN) grade II or III after they were evaluated at the clinic. Of the 367 cases of biopsy-proven cervical HPV, only 33 (9%) were recorded on Papanicolaou smears performed immediately before the biopsy, and 140 (38%) also had concomitant, biopsy-proven CIN, grade II or III. Of the 195 instances in which the colposcopic impression was simple HPV without CIN, 46 (24%) had high-grade CIN on biopsy. We conclude that the proportion of patients with HPV-associated problems is increasing, that the Papanicolaou smear is not sensitive in detecting cervical HPV infections, that patients with HPV changes found on Papanicolaou smears should be evaluated with colposcopy and that lesions that appear colposcopically to be simple HPV should undergo biopsy to rule out the presence of high-grade CIN.     

Synchronous Ovarian and Cervical Squamous Intraepithelial Neoplasia: An Analysis of HPV Status

In contrast to the strong association between human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN), the relationship between HPV and squamous epithelial lesions of the ovary is less clear. We report a case of synchronous ovarian and cervical squamous intraepithelial neoplasia. To investigate the possible association between HPV and squamous intraepithelial neoplasia/carcinomain situ(CIS) of the ovary, DNA was extracted from paraffin-embedded tissues including normal cervix, CIN, CIS from both ovaries, and an area of ovarian endometriosis. All samples were positive for HPV 16 E6 except for one of the two samples from the normal cervical squamous epithelium. These results support the hypothesis that HPV may be involved in the development of ovarian squamous intraepithelial neoplasia.     

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.