ReviewAdenocarcinoma: A unique cervical cancer
Introduction
Carcinoma of the cervix has showed a marked decline in developed countries over the past 40 years, due to wider implementation of cytologic screening and increased detection of premalignant disease. Although the decline is mainly attributable to a decrease in incidence of the most common histologic variant, squamous cell carcinoma (SCC), there has also been an increase in relative and absolute incidence of adenocarcinoma and adenosquamous carcinoma (AC) of the uterine cervix over the same period, especially among younger women [1], [2], [3], [4], [5], [6], [7], [8]. The relative increase in the proportion of AC has resulted in this histology comprising more than 20% of all cervical cancers in North America [3], [5], [6], [9].
Most of our knowledge on the treatment of cervical cancer comes from studies where the majority of the patients had SCC; AC only comprised on average 10% of the cases [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21]. Very few of these studies reported separate outcome results for AC of the cervix even on exploratory subset analyses. No prospective study has focused on the treatment of AC as the sole histology. As a consequence, our understanding of the natural history and optimal management of AC is limited. For the purposes of this review, the two most common histologies of non-SCC, adenocarcinoma and adenosquamous carcinoma of the cervix, will be labeled as AC and analyzed together given the scarce data separating these two histologies.
It appears that AC and SCC of the cervix behave differently. They are different in epidemiology, prognostic factors, and patterns of failure after similar treatments. Available data suggest that they may also differ in their response to treatment. We postulate that new treatment strategies specifically tailored to AC should be explored.
The purpose of this review was to give an overview of the current knowledge on AC of the cervix and its differences from SCC and to focus on possible therapeutic directions to explore in their management.
Section snippets
Literature search strategy
The literature was searched using MEDLINE (OVID: 1950 through December 2008) and EMBASE (OVID: 1988 through December 2008), using combined disease-specific terms (uterine cervix neoplasms/ or cervi:.ti AND cancer:.ti or neoplasms/ or carcinoma:.ti or adenocarcinoma:.ti or adenosquamous:.ti) with outcome-specific terms (prognosis/ or treatment/). The search was restricted to English language and humans. Additionally, Pubmed was searched with terms “adenocarcinoma” or “adenosquamous” and
Differences in epidemiology
Over the past 40 years multiple reports have documented the increase in relative distribution of AC compared to SCC in developed countries [4], [7]. Eifel et al. [9] reported between 1960 and 1989 the proportion of patients with AC increased 24% to 49% while the proportion of patients with SCC remained stable at 32%. Similar findings were observed from nine US-based Surveillance, Epidemiology, and End Results (SEER) registries [3]. Overall, from 1973 to 1996, the incidence of invasive cervical
Prognostic factors and differences in survival
Controversy exists as to whether histologic type is an independent prognostic factor for survival. Although some studies have shown no differences in survival between AC and SCC [28], [29], [30], [31], [32], [33], the majority have shown that AC carries a worse prognosis with 10%–20% differences in 5-year overall survival rates [9], [34], [35], [36], [37], [38], [39], [40], [41]. The most important prognostic factors for survival are clinical stage and lymph node status.
Clinical stage is a
Differences in patterns of dissemination and recurrences
Differences in patterns of disease dissemination have been reported for patients with AC histology. Shimada et al. [51] reported on the largest series of 3471 surgically treated stage IB–IIB cervix cancers where 52 patients (1.5%) had ovarian metastasis (23/52 SCC and 29/52 AC). Patients with AC had a significantly higher rate of ovarian metastasis (5% vs. 0.8%, p < 0.01). This difference was also observed stage for stage; in stage IB, 4% of AC had ovarian metastasis compared to 0.2% of SCC,
Differences in response to treatment in randomized trials
Current standard treatment of AC has evolved through Level 1 evidence from trials incorporating SC and AC, but with a minority proportion of AC (from 9% to 21%). Few studies have reported unplanned subset analyses of response rate or survival for AC [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21]. However, three randomized trials report subgroup analyses by cell type and demonstrate that treatments can have different effects on recurrence rates and survival.
A phase III
Differences in response to chemotherapy
Patients regardless of histology who present with metastatic, persistent, or recurrent carcinomas of the cervix continue to have very poor prognosis. Most studies evaluating chemotherapy in this setting have insufficient numbers of patients to come to any accurate conclusions regarding treatment of AC as a separate entity. However, there are studies that have attempted to evaluate the response of AC to chemotherapy.
Curtin et al. [54] reported on a series of 42 patients with histologically
Future directions and conclusions
Based on hypotheses developed from review of limited available data unique to AC on patterns of disease dissemination and risks of failure after conventional treatment, several summary statements can be made for patients with AC of the cervix.
For patients with small tumors < 2 cm in size and negative LVSI, the survival difference between AC and SCC is negligible. Surgical management with radical hysterectomy or radical trachelectomy for these carefully selected patients result in low recurrence
Conflict of interest statement
Conflict of interest statementThe authors have no conflicts of interest to declare.
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