Atypical squamous cells of undetermined significance in liquid-based cytologic specimens: results of reflex human papillomavirus testing and histologic follow-up in routine practice with comparison of interpretive and probabilistic reporting methods.

Human papillomavirus (HPV) DNA testing for high-risk types after Papanicolaou (Pap) smear interpretations of atypical squamous cells of undetermined significance (ASCUS) is a sensitive method for identifying women who harbor underlying high-grade squamous intraepithelial lesions (HSIL). To the authors' knowledge, the application of HPV testing to ASCUS smears in routine practice with comparison of probabilistic and interpretive models of cytologic reporting has not been reported. HPV DNA testing was performed reflexively on 216 liquid-based Pap smears that initially were interpreted as ASCUS. According to the interpretive model, ASCUS interpretations were modified and reported as either low-grade squamous intraepithelial lesions (LSIL) or squamous intraepithelial lesions (SIL) when HPV positive and as reactive when HPV negative. Using the probabilistic model, ASCUS interpretations were maintained and simply reported with the HPV test result. Histologic follow-up data were obtained. Of the 216 women with ASCUS cytology, 142 (65.7%) were positive for high-risk HPV types. Of the 142 HPV-positive ASCUS smears, 101 (71.1%) were modified to an interpretation of LSIL (96 cases) or SIL (5 cases). Histologic follow-up of 55 of the 101 HPV-positive smears in the interpretive group and 26 of the 41 HPV-positive smears in the probabilistic group yielded similar percentages of lesions (18 lesions [32.7%] and 9 lesions [34.6%], respectively). However, there was a preponderance of low-grade lesions in the interpretive group (89%) but a nearly equal distribution of low-grade and high-grade lesions in the probabilistic group (56% and 44%, respectively); overall, 22% of the lesions were high-grade. Of the 74 HPV-negative ASCUS smears, 71 (96%) were modified to reactive and all 5 with histologic follow-up were judged as negative. Colposcopy with tissue studies was virtually restricted to HPV-positive cases, regardless of the reporting model used, suggesting that clinicians are basing colposcopy triage on the HPV test result rather than the definitiveness of the cytologic interpretation. This observation, the similar yield of lesions in both groups, and the significant risk of high-grade lesions argue against application of the interpretive model to HPV-tested ASCUS cases.

Levi AW ，Kelly DP ，Rosenthal DL ，Ronnett BM ... -  《CANCER》

Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results.

Manos MM ，Kinney WK ，Hurley LB ，Sherman ME ，Shieh-Ngai J ，Kurman RJ ，Ransley JE ，Fetterman BJ ，Hartinger JS ，McIntosh KM ，Pawlick GF ，Hiatt RA ... -  《JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION》

Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity, specificity, and frequency of referral.

Kulasingam SL ，Hughes JP ，Kiviat NB ，Mao C ，Weiss NS ，Kuypers JM ，Koutsky LA ... -  《JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION》

Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia.

Arbyn M ，Buntinx F ，Van Ranst M ，Paraskevaidis E ，Martin-Hirsch P ，Dillner J ... -  《-》

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: diagnostic performance, human papillomavirus testing, and follow-up results.

Current guidelines recommend colposcopy rather than high-risk human papillomavirus (HPV) testing for the evaluation of abnormal cervical cytology interpreted as "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" (ASC-H) based on data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion (ASCUS/LSIL) Triage Study (ALTS), which indicated that ASC-H had a significantly greater frequency of high-risk HPV positivity and underlying high-grade squamous intraepithelial lesions (HSIL) compared with ASCUS. The cytologic interpretations in the ALTS were expert consensus diagnoses rather than routine, single-pathologist readings. The authors conducted a comparative analysis of Hybrid Capture 2 high-risk HPV positivity and frequency of histologically diagnosed HSIL for ASC-H and ASCUS to evaluate the performance of ASC-H as a cytologic interpretation subcategory and the potential utility of HPV testing for colposcopy triage of ASC-H in routine practice. Sixty-four of 96 patients with ASC-H (66.7%) were HPV-positive compared with 484 of 1079 patients with ASCUS (44.9%). Among the patients who had histologic follow-up, HSIL was identified in 18 of 45 patients (40.0%) with HPV-positive ASC-H compared with 27 of 266 patients (10.2%) with HPV-positive ASCUS (P < 0.0001) and 1 of 22 patients (4.5%) with HPV-negative ASC-H (P = 0.003); the latter result was similar to the finding of HSIL in 5 of 85 patients (5.9%) with HPV-negative ASCUS. The frequency of HPV-positive ASC-H in the current study (67%) was lower than that obtained in the ALTS for ASC-H (86%) but higher than that for ASCUS in both this study (45%) and in the ALTS (51% for all ASC; 63% for ASCUS, equivocal for LSIL). Underlying HSIL was detected in a similar percentage of patients with HPV-positive ASC-H in this study and in the ALTS (41%). The greater frequency of HPV positivity and the significantly increased risk of underlying HSIL for ASC-H compared with ASCUS indicated that ASC-H category utilization and performance are appropriate in this routine clinical practice setting. The lower frequency of HPV positivity for ASC-H compared with the ALTS data and the similar low risk of HSIL in HPV-negative ASC-H and HPV-negative ASCUS indicate that HPV testing for triage of ASC-H in routine practice has the potential to reduce the number of women who are referred for colposcopy without an increased risk of failure to detect HSIL among HPV-negative women, similar to its triage role for ASCUS.

Srodon M ，Parry Dilworth H ，Ronnett BM 《CANCER》