HPV triage is optimal management for ASCUS [Classics Series]

1. A single human papillomavirus (HPV) test identified 92.4% of women diagnosed with CIN-III.

2. A strategy of HPV triage testing detected high-grade intraepithelial lesion (HSIL) with 72% sensitivity, compared to 54% with immediate colposcopy and 55% with conservative management strategies.

3. In the HPV triage arm, 56% of women were referred for colposcopy whereas 100% and 12% of women in the immediate colposcopy and conservative management arms, respectively, underwent cervical biopsy.

Original date of publication: June 2003

Study Rundown: Over the past 3 decades, the incidence of and mortality associated with cervical cancer has precipitously dropped by over 50% due to improvements in screening programs. However, while detecting cervical cancer is the primary goal of screening, protecting women from invasive, painful and unnecessary diagnostic tests is similarly important given the progressive decline in disease prevalence. Overtreatment of lesions that are likely to regress increases healthcare costs and patient anxieties. Atypical cells of undetermined significance (ASCUS) represents the most common cytologic abnormality yet is the least likely to represent HSIL because 30-60% of ASCUS lesions are not related to HPV.

Researchers compared three management strategies for ASCUS pap: immediate colposcopy, HPV triage with repeat cytology or conservative management (repeat cytology). Findings demonstrate that HPV triage was at least as sensitive as immediate colposcopy and spared about 50% of women from unnecessary cervical biopsy. Strengths include randomized design, 2-year follow-up period and clinically relevant study endpoints. Although researchers requested pap slides for centralized review, the preparation of conventional pap slides is imprecise such that results might be biased away from the null since patients in the HPV triage arm received liquid-based pap along with their HPV test. This study was performed prior to the distinction between ASCUS and ASC-H (atypical squamous cells, cannot exclude high-grade) which likely overestimated the 5-year risk of HSIL with the HPV triage management strategy for ASCUS.

Click to read the study in the AJOG (American Journal of Obstetrics and Gynecology)

Background reading: Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors

In-Depth [randomized trial]: A total of 3488 women receiving care at 1 of 4 large academic centers for an ASCUS Pap were randomized to 1 of 3 initial management strategies: immediate colposcopy, HPV triage (HPV testing and liquid-based Pap with colposcopy referral for HPV+ or HSIL pap) conservative management (repeat cytology with colposcopy referral for HSIL pap). Regardless of initial management group, all women underwent cytology every 6 months for 2 years. All women underwent colposcopy at the conclusion of the 2-year study and those with a histologic diagnosis of HSIL or those with persistent LSIL at study exit were offered cervical excision procedure. Primary outcome was 2-year cumulative incidence of cervical intraepithelial neoplasia grade III (CIN-III).

Immediate colposcopy, where 100% of women were referred to colposcopy, detected 53.6% of CIN-3 cases over a cumulative 2-year period. The HPV triage strategy referred 55.6% of women for colposcopy with a sensitivity of 72.3%. The conservative strategy referred 12.3% of women for colposcopy and detected 54.6% of CIN 3 cases. The cumulative 2-year diagnosis of CIN-III was 8-9% in all study arms.

More from this author: Risks of trial of labor after cesarean delivery (TOLAC) [Classics Series], Vaginal progesterone for sonographic short cervix decreased preterm birth [Classics Series], Progesterone injections reduce recurrent preterm birth [Classics Series], Recurrent pregnancy loss associated with increased cardiovascular morbidity 

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