Characteristics of 44 cervical cancers diagnosed following Pap-negative, high risk HPV-positive screening in routine clinical practice

Objective: To characterize the cervical cancers diagnosed following a Pap-negative, high risk human papillomavirus (HPV)-positive (Pap-/HPV+) screen in routine clinical practice. Methods: Using data from Kaiser Permanente Northern California, we investigated the cases of cervical cancer diagnosed between January, 2003 and January, 2009 following Pap-/HPV+ screen. Two cervical specimens were routinely collected for cervical cancer screening, one for conventional cytology and the other for high risk HPV testing using Hybrid Capture 2 (Qiagen). Results: Forty-four women (median age at diagnosis = 44 years) were diagnosed with primary invasive cervical cancer with a recent history of one or more Pap-/HPV+ screens. Twenty-six women had one Pap-/HPV+ screen preceding the diagnosis of cancer, 15 had two, and three had three. There were 16 squamous cancers, one small cell cancer, 24 adenocarcinomas, 2 adenosquamous carcinomas, and one case with separate invasive squamous and adenocarcinoma. FIGO Stage was IA in 11 women, IB in 31 women and IIA in 2 women. Treatment included a pelvic node dissection in 30, 2 (6.7%) of whom had positive nodes. Conclusions: HPV testing contributes to early cervical cancer diagnosis detection in women with negative Pap tests. Most women in this cohort have early stage, node negative, treatable and potentially curable disease. Adenocarcinoma predominated as might be expected because cytology misses these cancers and their precursors. The majority of cancers were diagnosed following a single Pap-/HPV+ screen, suggesting that effective triage to colposcopy of women with a Pap-/HPV+ screen would be preferable to retesting in one year as currently recommended.