Cervical Adenocarcinoma and Squamous Cell Carcinoma Incidence Trends Among White and Black Women in the United States

Abstract & Commentary

Synopsis: Changes in screening, endocervical sampling, nomenclature, and improvements in treatment likely explain the increased in situ cervical SCC incidence in white and black women. Increasing AIS incidence over the past 20 years in white women has not yet translated into a decrease in invasive AC incidence.

Source: Wang S, et al. Cancer. 2004;100:1035-1044.

It is widely recognized that cervix cancer incidence rates have declined greatly in the United States following introduction of the Papanicolaou smear. However little is known about these rates among different histological subtypes. Wang and colleagues from the National Cancer Institute analyzed the Surveillance, Epidemiology, and End Results (SEER) database to evaluate this trend for a 25-year period, ending in the year 2000. The SEER Program collects data from 9 geographically distinct population-based cancer registries and is available for public analysis. Incidence rates by histologic subtype, namely adenocarcinoma and squamous cell carcinoma, race, age and disease stage were computed and analyzed for trends.

For both races, overall incidence of invasive squamous cell carcinoma declined over time and the majority of tumors currently detected are carcinoma in situ and localized cancers. Most striking was an increase in the incidence of squamous cell insitu disease reported over the final decade of analysis. Adenocarcinoma in situ rates among both races has increased and adenocarcinoma incidence has increased among young white women. In black women, invasive adenocarcinoma increases with age. Wang and colleagues conclude that changes in screening, endocervical sampling, nomenclature and improvements in treatment likely explain the increased squamous cell carcinoma in situ and decreased invasive squamous cell carcinoma incidence rates among both races. However, unlike this histology, the increased incidence of adenocarcinoma in situ diagnosis has not yet translated into a decreased incidence of invasive adenocarcinoma. The relationship of adenocarcinoma incidence and age among black women may reflect lack of effective screening or differential disease etiology.

Comment by Robert L. Coleman

One of the greatest successes in cancer prevention in the United States is undoubtedly the Pap smear. Introduced to a speculative audience by Dr. Papanicolaou in the 1940s, the Pap smear is now ubiquitously available, the focus of National screening programs (such as the National Breast and Cervical Cancer Early Detection Program) and individually responsible for a dramatic decrease in disease-specific mortality witnessed over the last 60 years. In many ways it is the ideal screening tool for a disease, which, by its nature, is "screen-able." Yet nearly half of new cervical cancer cases occur in women either previously unscreened or infrequently screened.

In this study, Wang et al accessed the SEER Program to evaluate recent trends in the diagnosis of "significant" lesions (in situ, localized, regional and advanced) by histology (squamous cell vs adenocarcinoma), race (white and black), and age. This database represents about 10% of the US population and has been particularly useful in providing insight into population-based cancer trends. While inconsistencies in data reporting and lack of precise parity with individual cancer staging criteria are limiting, the large number of available patients allows analysis of otherwise inevaluable trends and rare diagnoses. In the current study, the strength of the database is used to evaluate cancer trends of the uncommon adenocarcinoma histology and its incidence among different races and ages. What is of particular interest is the relationship of in situ disease and cancer. It would seem logical that if our efforts in screening were successful, we should identify more pre-invasive conditions resulting in declining rates of cancer. This "stage" migration effect is clearly confirmed among both races for squamous lesions. Unfortunately, the same has not yet been realized for adenocarcinoma lesions, particularly among black women. In recent years, cytopathologists and investigators have not only become more savvy in making these diagnoses on Pap smears but also have modified the criteria of reporting these lesions so as to not confuse them with their squamous counterparts. However, many studies continue to report not only increasing adenocarcinoma to squamous cell carcinoma ratios but also real increases in new adenocarcinoma diagnoses. In the current study, adenocarcinoma incidence is increasing, particularly among young (25 to 34 year-old) white women and in all age groups of black women. Interestingly, incidence rates of invasive adenocarcinoma plateau at about age 35 for white women yet continue to increase in blacks, being highest in the 75 and older cohort. If screening practices are equivalent, why is this effect being seen?

The answer is not immediately available in the current report. However, some hypotheses may be drawn in evaluating known risk factors for invasive adenocarcinoma and balancing these against population trends over the study time interval. Nulliparity and obesity have been associated with cervical adenocarcinoma risk and both have increased in recent years. Although a hormone effect from endogenous obesity may influence incidence, it has been hypothesized that just the occurrence of obesity may interfere with effective population-based screening and complicating detection. Still, the age-effect seen between the races suggests an etiological factor not heretofore identified. HPV-18 is most often HPV subtype associated invasive cervix adenocarcinoma. It is unknown if prevalence rates have altered over the last 25 years or whether the cofactors previously mentioned interact with this viral infection to effect this observation. More mechanistic investigation is needed.

In the big picture, significant progress is being made in the United States thanks to the tireless efforts of our healthcare providers. More needs to be done to ensure that all women are appropriately screened and managed for pre-invasive disease. However, the worldwide burden problem cannot be overlooked and it is hoped an effective model can be enacted in those high-risk populations where resources are more limited.

Robert L. Coleman, MD, Dept. of Gynecologic Oncology, University of Texas Southwestern Medical Center, Dallas, TX, is an Associate Editor for OB/GYN Clinical Alert.

Suggested Reading

1. Altekruse SF, et al. Am J Obstet Gynecol. 2003; 188:657-663.
2. Hiatt RA, et al. J Natl Cancer Inst. 2002;94:1837-1846.
3. Lacey JV Jr, et al. Cancer. 2003;98:814-821.
4. Smith HO, et al. Gynecol Oncol. 2000;78:97-105.
5. Solomon D, et al. JAMA. 2002;287:2114-2119.