Prognostic value of histopathology and trends in cervical cancer: a SEER population study

Abstract

Background: Histopathology is a cornerstone in the diagnosis of cervical cancer but the prognostic value is controversial.

Methods: Women under active follow-up for histologically confirmed primary invasive cervical cancer were selected from the United States Surveillance, Epidemiology, and End Results (SEER) 9-registries public use data 1973-2002. Only histologies with at least 100 cases were retained. Registry area, age, marital status, race, year of diagnosis, tumor histology, grade, stage, tumor size, number of positive nodes, number of examined nodes, odds of nodal involvement, extent of surgery, and radiotherapy were evaluated in Cox models by stepwise selection using the Akaike Information Criteria.

Results: There were 30,989 records evaluable. From 1973 to 2002, number of cases dropped from 1,100 new cases/year to 900/year, but adenocarcinomas and adenosquamous carcinoma increased from 100/year to 235/year. Median age was 48 years. Statistically significant variables for both overall and cause-specific mortality were: age, year of diagnosis, race, stage, histology, grade, hysterectomy, radiotherapy, tumor size and nodal ratio. The histological types were jointly significant, P < 0.001. Cause-specific mortality hazard ratios by histological type relatively to non-microinvasive squamous cell carcinoma were: microinvasive squamous cell carcinoma 0.28 (95% confidence interval: 0.20-0.39), carcinoma not otherwise specified 0.91 (0.79-1.04), non-mucinous adenocarcinoma 1.06 (0.98-1.15), adenosquamous carcinoma 1.35 (1.20-1.51), mucinous adenocarcinoma 1.52 (1.23-1.88), small cell carcinoma 1.94 (1.58-2.39).

Conclusion: Small cell carcinoma and adenocarcinomas were associated with poorer survival. The incidental observation of increasing numbers of adenocarcinomas despite a general decline suggests the inefficiency of conventional screening for these tumors. Increased incidence of adenocarcinomas, their adverse prognosis, and the young age at diagnosis indicate the need to identify women who are at risk.

Figure 1

Numbers of new cervical cancers, by histopathological type. All graphs are centered around the mean number of cases per year (horizontal line). The vertical axes are scaled to highlight the trend within each histopathological type.

Figure 2

Overall survival by histopathology group. (a) Unadjusted Kaplan-Meier survival estimates. (b) Expected survival after adjustment taking into account registry area, age, year of diagnosis, race, marital status, grade, stage, surgery and radiotherapy, for a theoretical patient presenting with average characteristics of the population.

Figure 3

Ranking of histopathological types by cause-specific mortality hazard ratios. The hazard ratios were computed taking into account registry area, age, year of diagnosis, race, marital status, grade, stage, surgery, and radiotherapy. Horizontal bars: 95% confidence interval. Size of the boxes drawn as a function of the number of patients.

Figure 4

Numbers of newly diagnosed in situ carcinomas per year. The plots were centered around the respective means and were scaled by dividing with the respective standard deviations.