Liquid-Based Cytology and Human Papillomavirus Testing to Screen for Cervical Cancer: A Systematic Review for the US Preventive Services Task Force

Background: Screening programs using conventional cytology have successfully reduced cervical cancer, but newer tests might enhance screening. Purpose: To systematically review the evidence on liquid-based cytology (LBC) and high-risk human papillomavirus (HPV) screening for U.S. Preventive Services Task Force use in updating its 2003 recommendation. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2000 through September 2010. Study Selection: Two independent reviewers selected fair-to good-quality English-language studies that compared LBC or HPV-enhanced primary screening with conventional cytology in countries with developed population-based screening for cervical cancer. Data Extraction: At least 2 independent reviewers critically appraised and rated the quality of studies and used standardized abstraction forms to extract data about test performance for detecting cervical intraepithelial neoplasia (CIN) and cancer and screening-related harms. Data Synthesis: On the basis of 4 fair-to good-quality studies (141 566 participants), LBC had equivalent sensitivity and specificity to conventional cytology. Six fair- to good-quality diagnostic accuracy studies showed that 1-time HPV screening was more sensitive than cytology for detecting CIN3+/CIN2+ but was less specific. On the basis of 2 fair- to good-quality randomized, controlled trials (RCTs) (120 533 participants), primary HPV screening detected more cases of CIN3 or cancer in women older than 30 years. Four fair- to good-quality diagnostic accuracy studies and 4 fair- to good-quality RCTs showed mixed results of cotesting (HPV plus cytology) in women aged 30 years or older compared with cytology alone, with no clear advantage over primary HPV screening. Incomplete reporting of results for all screening rounds, including detection of disease and colposcopies, limits our ability to determine the net benefit of HPV-enhanced testing strategies. Limitation: Resources were insufficient to gather unpublished data, short-term trial data showed possible ascertainment bias, and most RCTs used protocols that differed from current U. S. practice. Conclusion: Evidence supports the use of LBC or conventional cytology for cervical cancer screening, but more complete evidence is needed before HPV-enhanced primary screening is widely adopted for women aged 30 years or older.