Bergeron Christine, Giorgi-Rossi Paolo, Cas Frederic, Schiboni Maria Luisa, Ghiringhello Bruno, Dalla Palma Paolo, Minucci Daria, Rosso Stefano, Zorzi Manuel, Naldoni Carlo, Segnan Nereo, Confortini Massimo, Ronco Guglielmo
Department of Pathology, Laboratoire Cerba, Cergy Pontoise France (CB, FC); Servizio Interaziendale Epidemiologia, AUSL Reggio Emilia, Italy (PGR); Department of Pathology, S. Giovanni Hospital, Rome, Italy (MLS); Laboratory Department University Hospital "Città della Salute e della Scienza di Torino," Turin, Italy (BG); Department of Pathology, S. Chiara Hospital, Trento, Italy (PDP); Women's Health Department, University Hospital, Padua, Italy (DM); Veneto Oncology Institute IRCCS, Padua, Italy (MZ); Emilia-Romagna Region, Bologna, Italy (CN); Laboratory of Preventive Oncology, Institute for Cancer Study and Prevention (ISPO), Florence (MC); Department of Cancer Screening, Center for Epidemiology and Prevention in Oncology (CPO), University Hospital "Città della Salute e della Scienza di Torino," Turin, Italy (GR, NS, SR).
J Natl Cancer Inst. 2015 Jan 7;107(2). doi: 10.1093/jnci/dju423. Print 2015 Feb.
Human papillomavirus (HPV)-based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status.
Women age 25 to 60 years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV testing with cytology were referred to colposcopy if HPV positive and, if no cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV negativity. Cytological slides taken at the first colposcopy were retrieved and independently interpreted by an external laboratory, which was only aware of patients' HPV positivity. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were computed for histologically proven CIN2+ with HPV status-informed cytology for women with a determination of atypical squamous cells of undetermined significance (ASCUS) or more severe. All statistical tests were two-sided.
Among HPV-positive women, informed cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of 85.6% (95% confidence interval [CI] = 76.6 to 92.1), 65.9% (95% CI = 63.1 to 68.6), 16.2% (95% CI = 13.0 to 19.8), and 1.7 (95% CI = 0.9 to 2.8), respectively. Cytology was also associated with subsequent risk of newly diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs blind cytology obtained by referring to colposcopy and following up only HPV positive women who had HPV status-informed cytology greater than or equal to ASCUS was 1.58 (95% CI = 1.22 to 2.01), while the corresponding relative referral to colposcopy was 0.95 (95% CI = 0.86 to 1.04).
Cytology informed of HPV positivity is more sensitive than blind cytology and could allow longer intervals before retesting HPV-positive, cytology-negative women.
基于人乳头瘤病毒（HPV）的筛查需要分流。在大多数关于HPV检测及细胞学分流的随机对照试验（RCT）中，细胞学判读对HPV状态是盲法的。
年龄在25至60岁之间、参加宫颈癌新技术（NTCC）RCT（比较HPV检测与细胞学检查）的女性，若HPV检测呈阳性则转诊至阴道镜检查；若未检测到宫颈上皮内瘤变（CIN），则随访至HPV转阴。收集首次阴道镜检查时的细胞学玻片，并由外部实验室进行独立判读，该实验室仅知晓患者的HPV阳性情况。计算经组织学证实为CIN2+且具有HPV状态告知细胞学结果的女性（其细胞学诊断为意义不明确的非典型鳞状细胞（ASCUS）或更严重病变）的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）。所有统计检验均为双侧检验。
在HPV阳性女性中，知晓HPV状态的细胞学检查对CIN2+的横断面敏感性、特异性、PPV和1-NPV分别为85.6%（95%置信区间[CI]=76.6至92.1）、65.9%（95%CI=63.1至68.6）、16.2%（95%CI=13.0至19.8）和1.7（95%CI=0.9至2.8）。细胞学检查还与新诊断CIN2+和CIN3+的后续风险相关。对于CIN2+，通过转诊至阴道镜检查并仅随访HPV阳性且具有知晓HPV状态的细胞学检查结果大于或等于ASCUS的女性，其横断面相对敏感性（与盲法细胞学检查相比）为1.58（95%CI=1.22至2.01），而相应的相对转诊至阴道镜检查率为0.95（95%CI=0.86至1.04）。
知晓HPV阳性情况的细胞学检查比盲法细胞学检查更敏感，并且可以延长对HPV阳性、细胞学检查阴性的女性进行再次检测的间隔时间。
