To clarify the contribution of cytology to the earlier diagnosis of invasive cervical cancer as part of screening cotesting every 3 years.
Women who underwent cotesting within Kaiser Permanente Northern California over the period 2003 through 2013 and subsequently were diagnosed with invasive cervical cancer were identified. Completeness of ascertainment of cancer cases was verified by comparison to the Northern California SEER registry. Laboratory results and clinical records were reviewed to establish the contribution of the screening cytology component of cotesting to the diagnosis of invasive cervical cancer.
From 2003 through 2013, 699 women underwent cotesting at KPNC prior to the diagnosis of invasive cancer. One hundred seventy (24%) of the 699 cancers had at least one HPV-negative cotest at any time interval prior to the diagnosis. Of the 170 women with one or more HPV negative results, 116 (68%) and 39 (23%) were Pap negative and positive, respectively. Fifteen women (9%) had both Pap negative and Pap positive diagnoses. The following clinical settings characterized this heterogeneous group (categories are not mutually exclusive):
Most recent Pap positive HPV negative result > 3 years before cancer diagnosis: 7
Probable Stage 2 Adenocarcinoma of the endometrium: 5
Cancer biopsy before results of cotest returned: 9
Symptomatic from cancer or clinically apparent cancer on exam at testing visit: 7
Cotested as part of follow-up of a previous positive HPV test: 3
Subsequent positive HPV test prior to diagnosis: 11
Cotest result was ASC-US HPV negative (for which followup testing in 3 years is recommended): 14
Of the 54 women with HPV-negative, Pap-positive results prior to a cancer diagnosis, a maximum of 14/699 (2%) of women might have had their primary cervical cancer diagnosed earlier because of the inclusion of cytology as part of their screening cotest conducted within 3 years of cancer diagnosis. During the study period, 2,438,474 cotests were performed in KPNC.
The majority of women with HPV-negative cotests prior to a cancer diagnosis were also Pap-negative. Of the 54 women with Pap-positive HPV-negative cotests reported from KPNC prior to the diagnosis of cervical cancer, most were either not screening tests, were associated with cancer likely originating from the endometrium, had ASC-US cytology or had a subsequent positive HPV test prior to the cancer diagnosis. Description of the clinical context of testing is required to accurately characterize the potential contribution of including cytology in screening cotesting to the diagnosis of invasive cervical cancer.