Human Papillomavirus Test Results Research Articles

Human papillomavirus testing as triage for atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions: Sensitivity, specificity, and cost-effectiveness

OBJECTIVE: Our purpose was to evaluate the cost-effectiveness of the use of a Food and Drug Administration–approved human papillomavirus test in triaging patients with Papanicolaou smears showing atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion for colposcopy compared with an algorithm that used cytologic follow-up. STUDY DESIGN: Four hundred sixty-two women referred to our Colposcopy Clinic with a Papanicolaou smear report of atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion underwent repeat Papanicolaou smear, cervical colposcopy, directed cervical biopsy, and endocervical curettage. In addition, human papillomavirus testing by the Food and Drug Administration–approved HPV Profile (Digene Diagnostics, Silver Spring, Md.) test was done. A comparision of sensitivity, specificity, and cost-effectiveness of an algorithm determining the need for colposcopy on the basis of repeat cytologic testing versus an algorithm that incorporated repeat cytologic testing and human papillomavirus screening was done. The cost-effectiveness of both of these triage algorithms was also compared. RESULTS: As expected, high-risk human papillomavirus deoxyribonucleic acid was detected with greater frequency in relation to increasing severity of cervical intraepithelial neoplasia. In 268 women, the follow-up smear obtained in our clinic was reported as negative. High-risk human papillomavirus types were found in 23.5% of these women. In the human papillomavirus–negative women, 5.9% had grade 2 or 3 cervical intraepithelial neoplasia confirmed on cervical biopsy. In comparison, 20.6% of those with a positive result of the human papillomavirus test had grade 2 or 3 cervical intraepithelial neoplasia on biopsy ( p < 0.001). Despite this difference, the sensitivity of a positive result of a high-risk human papillomavirus test in predicting the presence of grade 2 or 3 cervical intraepithelial neoplasia was only 52%. Among the women for whom a follow-up clinic Papanicolaou smear was reported as showing atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion, there was no difference in the frequency of biopsy-proved grade 2 or 3 cervical intraepithelial neoplasia between those women with a positive human papillomavirus test result and those with a negative test result. Colposcopy would have been recommended for 194 women because of a repeat clinic smear revealing atypical squamous cells of undetermined significance, a low-grade squamous intraepithelial lesion, or a high-grade squamous intraepithelial lesion, and in 21.6% of these women grade 2 or 3 cervical intraepithelial neoplasia was shown on biopsy (sensitivity 63%, specificity 62%). Colposcopy would have been recommended for 180 women because high-risk human papillomavirus or a high-grade squamous intraepithelial lesion was detected at the clinic visit, and in 25% of this group grade 2 or 3 cervical intraepithelial neoplasia was evident on biopsy (sensitivity 67%, specificity 66%). Sensitivity and specificity were virtually identical for the two algorithms, but the cost of human papillomavirus testing was nearly double that of triage based on repeat cytologic testing alone ($692 vs $1246 per case). CONCLUSION: The Food and Drug Administration–approved HPV Profile test is not a cost-effective triage for patients referred with Papanicolaou smears reported as showing atypical squamous cells of undetermined significance or low-grade squamous lesions. (Am J Obstet Gynecol 1997;177:930-6.)

Human papillomavirus deoxyribonucleic acid detection in mildly or moderately dysplastic smears: A possible method for selecting patients for colposcopy

Objective: Current screening protocols for cervical cancer dictate that patients with smears read as mild or moderate dysplasia of the uterine cervix undergo colposcopy, although approximately half these women do not prove to have high-grade squamous intraepithelial lesions. The aim of this study was to determine whether human papillomavirus testing is capable of discriminating between high- and low-grade squamous intraepithelial lesions so as to be useful in reducing the number of colposcopic examinations. Study design: We tested 190 consecutive patients with smears read as mild or moderate dysplasia for the presence of human papillomavirus deoxyribonucleic acid by use of two different polymerase chain reactions with the consensus primer pairs CPI/IIG and MY09/11. Typing was carried out by direct sequence analysis of the CPI/IIG amplimers. The MY09/11 amplimers were detected in enzyme-linked immunosorbent assay format with the SHARP (Solution Hybridization Assay for PCR Products) Signal System with two probe mixtures (A and B) to detect nononcogenic and oncogenic human papillomavirus types. The human papillomavirus test results were compared with the histologic diagnosis, which was regarded as the reference standard. Results: Fifty-six of the 190 patients had high-grade squamous intraepithelial lesions. The sensitivity was 96% for the CPI/IIG test and 95% for the MY09/11 polymerase chain reaction plus SHARP Signal System when probe B only was used. The specificity was 33% for the CPI/IIG test and 40% for the MY09/11 polymerase chain reaction plus SHARP Signal System when probe B was used. Conclusion: A negative CPI/IIG or SHARP Signal System probe B test can select, respectively, 44 or 54 of the 134 patients without high-grade squamous intraepithelial lesions. The use of these human papillomavirus tests as a secondary triage in patients with smears that were read as mild or moderate dysplasia could prevent those patients from undergoing unnecessary colposcopy. However, respectively, 2 or 3 of the 56 patients who have high-grade squamous intraepithelial lesions would be missed by human papillomavirus testing.

Cervical specimens collected in liquid buffer are suitable for both cytologic screening and ancillary human papillomavirus testing

Several new techniques have been developed to improve the sensitivity of cervical carcinoma screening and reduce equivocal cytologic diagnoses referred to as atypical squamous cells of undetermined significance (ASCUS). This study evaluates the effectiveness of combining two newly introduced diagnostic techniques: preparation of thin-layer cytologic slides from ThinPrep liquid buffer and selected Hybrid Capture testing for human papillomavirus (HPV) DNA. Because HPV DNA detection has been strongly associated with the presence of a cervical carcinoma precursor ("squamous intraepithelial lesion," or SIL), HPV testing might be useful for identifying women with ASCUS who have an underlying SIL. Two hundred specimens demonstrating diverse cervical abnormalities were selected from a prospective population-based study of 9174 women conducted in Costa Rica. The entire cohort had been screened with conventional cervical smears; ThinPrep slides made from liquid buffer, PAPNET, a computerized slide reading system; and Cervicography. Patients with any abnormal screening test were referred for colposcopy, punch biopsy, and loop excision of cases with high grade cytologic abnormalities not explained by punch biopsy. For this investigation, the results of ThinPrep cytology and HPV testing alone and in combination were compared with the final diagnoses, with an emphasis on the detection of carcinoma and high grade SIL. The 200 subjects studied included 7 women with a final diagnosis of carcinoma, 44 with high grade SIL, 34 with low grade SIL, 51 with a variety of equivocal diagnoses, and 64 with normal diagnoses. A ThinPrep cytologic diagnosis of SIL or carcinoma was made in 39 (76%) of the 51 women with final diagnoses of high grade SIL or carcinoma. Hybrid Capture testing detected carcinoma-associated types of HPV DNA in 100% of women with carcinoma, 75% with high grade SIL, 62% with low grade SIL, 20% with equivocal final diagnoses, and 12% of normal women. If colposcopy referral had been limited to women with a ThinPrep diagnosis of SIL or a diagnosis of ASCUS associated with the detection of carcinoma-associated HPV DNA from the same vial, 100% of women with carcinoma and 80% with high grade SIL would have been examined. To achieve this high sensitivity in the entire population of 9174 women would have required the referral of about 7% of the population. The combined screening strategy would have performed marginally better than optimized conventional screening with referral of any abnormal cytology (ASCUS and above). A cervical carcinoma screening technique which uses a single sample for cytopathology and HPV testing to triage equivocal diagnoses may be promising if it proves to be cost-effective.

Cervical specimens collected in liquid buffer are suitable for both cytologic screening and ancillary human papillomavirus testing

BACKGROUND Several new techniques have been developed to improve the sensitivity of cervical carcinoma screening and reduce equivocal cytologic diagnoses referred to as atypical squamous cells of undetermined significance (ASCUS). This study evaluates the effectiveness of combining two newly introduced diagnostic techniques: preparation of thin-layer cytologic slides from ThinPrep liquid buffer and selected Hybrid Capture testing for human papillomavirus (HPV) DNA. Because HPV DNA detection has been strongly associated with the presence of a cervical carcinoma precursor (“squamous intraepithelial lesion,” or SIL), HPV testing might be useful for identifying women with ASCUS who have an underlying SIL. METHODS Two hundred specimens demonstrating diverse cervical abnormalities were selected from a prospective population-based study of 9174 women conducted in Costa Rica. The entire cohort had been screened with conventional cervical smears; ThinPrep slides made from liquid buffer; PAPNET, a computerized slide reading system; and Cervicography. Patients with any abnormal screening test were referred for colposcopy, punch biopsy, and loop excision of cases with high grade cytologic abnormalities not explained by punch biopsy. For this investigation, the results of ThinPrep cytology and HPV testing alone and in combination were compared with the final diagnoses, with an emphasis on the detection of carcinoma and high grade SIL. RESULTS The 200 subjects studied included 7 women with a final diagnosis of carcinoma, 44 with high grade SIL, 34 with low grade SIL, 51 with a variety of equivocal diagnoses, and 64 with normal diagnoses. A ThinPrep cytologic diagnosis of SIL or carcinoma was made in 39 (76%) of the 51 women with final diagnoses of high grade SIL or carcinoma. Hybrid Capture testing detected carcinoma-associated types of HPV DNA in 100% of women with carcinoma, 75% with high grade SIL, 62% with low grade SIL, 20% with equivocal final diagnoses, and 12% of normal women. If colposcopy referral had been limited to women with a ThinPrep diagnosis of SIL or a diagnosis of ASCUS associated with the detection of carcinoma-associated HPV DNA from the same vial, 100% of women with carcinoma and 80% with high grade SIL would have been examined. To achieve this high sensitivity in the entire population of 9174 women would have required the referral of about 7% of the population. The combined screening strategy would have performed marginally better than optimized conventional screening with referral of any abnormal cytology (ASCUS and above). CONCLUSIONS A cervical carcinoma screening technique which uses a single sample for cytopathology and HPV testing to triage equivocal diagnoses may be promising if it proves to be cost-effective. Cancer (Cancer Cytopathol) 1997; 81:89-97. © 1997 American Cancer Society.

Human papillomavirus detection by hybrid capture in paired cervicovaginal lavage and cervical biopsy specimens.

Infection of the uterine cervix with human papillomavirus (HPV) is associated with dysplastic lesions that may progress to malignancy. Certain HPV types are associated with higher risk of cervical cancer than other genital HPVs. The goal of this study was to determine if cells obtained by cervicovaginal lavage contain similar HPV types as paired cervical biopsy in women referred because of abnormal cervical cytology. Thirty-four paired lavage and biopsy samples were analyzed for HPV DNA by hybrid capture, using "low risk" (HPV types 6. 11, and related types and "high risk" group (HPV types 16, 18, and related types) HPV. HPV was detected in 24 lavage samples and 18 biopsies. High risk types were predominant. In 14 of 18 HPV-positive biopsies, the paired lavage was also positive for the same HPV group. Four biopsies were HPV-positive at low levels, and the paired lavage was HPV-negative. The mean viral copy numbers of the biopsies from patients with positive and negative lavage samples were 2.7 and 0.1, respectively (P = .02). Ten low level HPV infections were detected by lavage that were not detected by biopsy. HPV detection by hybrid capture in cells obtained by cervicovaginal lavage reflects the results of HPV testing in cervical biopsies.

Follow-up evaluation of cervicovaginal human papillomavirus infection in adolescents

We performed a second examination for human papillomavirus (HPV) DNA on 51 sexually experienced 13- to 21-year-old (mean = 17.8 years) female patients seen at an urban teaching hospital. Cervicovaginal lavages were performed 6 to 36 months apart (median = 13.3 months) to collect cells for HPV DNA detection and typing by Southern blot hybridization. At the first and second visits, 39.2% (20/51) and 25.5% (13/51) of patients, respectively, were infected with HPV. Collectively, 56.9% (29/51) of patients had at least one positive HPV test result. Although 7.8% (4/51) were infected with HPV at both visits, only one patient had infection with the same HPV type. These findings suggest that although HPV infection is a common sexually transmitted disease, genotype-specific HPV infection detected by Southern blot at two visits was rare.

Blood pressure, race and socioeconomic status in employed males: Jess F. Kraus, University of California, Department of Community Health, Davis, California; Nemat O. Borhani; Charles E. Franti

Questions have recently been raised about the acceptability of increased cervical cancer risk projected with the new guideline-recommended rescreening interval of 5 years after negative cytology and human papillomavirus (HPV) cotest results. Additional data sources capable of evaluating cervical cancer risk over time are being sought. We employed the continuously updated Bayesian Pittsburgh Cervical Cancer Screening Model (PCCSM) to estimate invasive cancer risks for patients screened at extended screening intervals after negative HPV test results.The analyzed database included cervical screening data collected over 10 years (2005-2014) at Magee Womens Hospital with 976,624 liquid-based cytology (LBC) results, 285,351 companion high-risk US Food and Drug Administration–approved HPV test results from LBC vials, and 112,435 follow-up histopathologic results from surgical procedures with cervical tissue sampling. Histopathologic cervical cancer risk estimates for patients with prior double negative results with cervical LBC and from-the-vial HPV cotesting were computed using the PCCSM for women rescreened at intervals ranging from 1 to 9 years. Similar risks were computed for women with any negative HPV test result, not considering cytology results.Histopathologic invasive cervical cancer risk computed following LBC and HPV cotesting double negative results progressively increased with rescreening intervals of 1 to 9 years. Cervical cancer risks computed following any HPV-negative result, not considering cytology results, were consistently even higher at each comparable extended rescreening interval.The PCCSM is a new data source that allows evaluation of cervical cancer risk over time. Cervical cancer risk is minimized with more frequent cytology and HPV cotesting.