Distribution of treatment for human papillomavirus-associated gynecologic carcinomas before prophylactic vaccine

Authors


  • We appreciate the thorough review by Dr. Cyril Spann.

  • The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

  • This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

BACKGROUND.

This report describes the distribution of treatment for cervix uteri, vagina, and vulva carcinomas by demographic characteristics before the widespread implementation of human papillomavirus (HPV) vaccination in the US.

METHODS.

The authors used data collected by the Surveillance, Epidemiology, and End Results Program from 2000 through 2004 to calculate the distribution of surgical procedures and radiotherapy by carcinoma site, disease stage, and tumor histology (squamous vs nonsquamous). For women with localized cervical carcinomas, the proportions of hysterectomy procedures were analyzed by age, race, ethnicity, marital status, and histology, including a 13-year trend analysis of hysterectomy use.

RESULTS.

Although 75% of the women with cervical carcinomas underwent hysterectomy, there were significant differences in treatment by race and ethnicity. Black women were least likely to undergo hysterectomies: The large gap between them and other racial/ethnic groups persisted throughout the study period. For all 3 carcinoma sites, both tumor histology and disease stage influenced radiotherapy modality and the extent of surgery. Nonsquamous histology, ages 30 to 64 years, Asian/Pacific Islander race, and marriage were associated positively with hysterectomy. Overall, a gradual decrease in hysterectomy use was observed over time. Hysterectomies among Hispanic white women increased slightly.

CONCLUSIONS.

Cancer surveillance data suggest that treatment patterns of HPV-associated carcinomas are correlated with both clinical and demographic characteristics. The decreasing use of hysterectomy before introduction of the HPV vaccine and the vaccine's potential effect on the age-related stage distributions warrant consideration when evaluating its future impact on the delivery of care for women with HPV-associated tumors. Cancer 2008;113(10 suppl):2926–35. Published 2008 by the American Cancer Society.

Epidemiologic studies have indicated a strong link between human papillomavirus (HPV) infection and certain types of gynecologic tumors, such as cervical, vaginal, and vulvar carcinomas.1–4 Despite the overall decrease in HPV-associated carcinoma rates, health disparities persist in incidence, mortality, survival, and screening practices across racial/ethnic groups, socioeconomic groups, and geographic regions.5–11 Recently in the US, the Food and Drug Administration approved the quadrivalent HPV vaccine for clinical use. Its introduction is expected to have a long-term impact on the epidemiology of HPV-associated gynecologic carcinomas.12–14

Multiple treatment options are available for cervical, vaginal, and vulvar carcinomas, including surgery alone, radiotherapy alone, radiosurgery, neoadjuvant chemotherapy and surgery, surgery and adjuvant radiotherapy, surgery and adjuvant chemotherapy, chemoradiotherapy, and chemotherapy alone.15–17 The choice of treatment generally depends on the extent of the disease, tumor histology, and comorbidities at the time of diagnosis.18 Several studies have described patterns of care within specific racial, marital status, and age subgroups and within selected geographic regions.19–22 However, to our knowledge recent treatment practices nationwide have not been well documented. Accordingly, there have been limited opportunities for the assessment of HPV-vaccination efficacy and impact on the quality of care, the quality of life, and healthcare costs in the US. Generally, surveillance programs provide adequate, inexpensive data for the assessment of public health interventions.23 We propose using treatment surveillance data collected by central cancer registries to evaluate the long-term impact of prophylactic vaccination on the delivery of care for HPV-associated tumors. The current analysis may help facilitate a future comparison of prevaccine and postvaccine treatment practices in the US by presenting empiric data concerning treatment trends and patterns as reported by cancer registries. This analysis does not intend either to compare the efficacy of various treatment modalities or to evaluate the compliance with current or past clinical practice guidelines.

We hypothesize that the same factors that are correlates of screening and access to care (age, race, ethnicity, marital status) may be associated with treatment of HPV-associated gynecologic cancers. This report describes the distribution of treatment administered for carcinomas of the cervix uteri, vagina, and vulva before the license approval of the first HPV vaccine in the US. In particular, the objectives of this study were to 1) describe the frequency distribution of locoregional treatment for HPV-associated gynecologic carcinomas by tumor characteristics and disease stage, 2) examine the frequency distribution of hysterectomies related to cervical cancer by demographic and tumor characteristics, and 3) examine the temporal trend of hysterectomy procedures for cervical carcinomas by demographic characteristics.

MATERIALS AND METHODS

Sources of Data and Case Selection

The study population included women diagnosed with cervical, vulvar, and vaginal carcinomas who, at the time of diagnosis, were residents of areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute.24 The SEER Program includes 23.4% of the white US population, 22.7% of the black US population, 53.3% of the Asian US population, 69.8% of the Pacific Islander US population, and 40.4% of the Hispanic US population.24 Except for the trend analysis, we based all of our analyses on SEER cases diagnosed between January 1, 2000, and December 31, 2004, to ensure a good representation of all racial groups.25 The trend analysis includes cases diagnosed between January 1, 1992, and December 31, 2004. Excluded from the trend analysis were 4 registries (Louisiana, New Jersey, Greater California, and Kentucky) that joined SEER in 2001 and 1 registry that reports Alaska Natives only (Alaska Natives Tumor Registry).24

In the selection process, we used the SEER Incidence Site Recode table based on the International Classification of Diseases for Oncology, 3rd edition (ICD-O-3), which is used commonly for presenting cancer statistics in the US. A detailed description of the histology codes included in this analysis (codes 8010-8671 and 8940-8941) is provided elsewhere in this supplement to Cancer.26 We analyzed vaginal and vulvar carcinomas separately, including grade 3 vaginal intraepithelial neoplasia (VAIN-3) (ICD-O-3 code 8077), which accounts for 79% of all in situ vaginal tumors, and grade 3 vulvar intraepithelial neoplasia (VIN-3) (ICD-O-3 code 8077), which accounts for 65% of all in situ vulvar tumors. The analysis did not include in situ cervical tumors (CIN-3), because the SEER Program discontinued the registration of these tumors (effective January 1, 1996). Also excluded were cases without histologic confirmation, cases for which the index HPV-associated neoplasm was not the first primary cancer, and cases first diagnosed at autopsy.

During the period from 2000 through 2004, there were 16,678 cases diagnosed with invasive cervical cancer; 2829 diagnosed with in situ or invasive vaginal cancer; and 11,365 diagnosed with in situ or invasive vulvar cancer. However, only 15,091 cases (90.5%) of cervical cancer, 1812 cases (64.1%) of vaginal cancer, and 8785 cases (77.3%) of vulvar cancer satisfied the selection criteria for inclusion in the current analysis. The percentages of excluded cases for vaginal and vulvar cancers were relatively high, primarily because the neoplasm of interest was not the first primary cancer.

Treatment Data

The standard rules and codes for collecting and reporting surgery and radiotherapy information were established by the Commission on Cancer of the American College of Surgeons (ACoS) and defined in the Facility Oncology Registry Data Standards (FORDS) manual.27 For the treatment analysis, we used standard cancer surveillance data that describe the surgery of the primary tumor and radiotherapy procedures. Information regarding chemotherapy and other therapeutic modalities, which are relatively rare for the cancers of interest, was not available.

Surgical procedures for cervical carcinoma treatment include local tumor destruction (ie, a surgical event with no pathologic specimen), local tumor excision (ie, a surgical event resulting in a specimen sent to pathology), and several hysterectomy techniques (eg, total, modified radical). Tumor destruction procedures include, but are not limited to, photodynamic therapy, fulguration, cryosurgery, laser, and thermal ablation. A loop electrocautery excision procedure (LEEP) is counted when the intent is to diagnose and cure the tumor. Local excision procedures include, but are not limited to, excisional biopsy, polypectomy and myomectomy, electrocauterization, cryosurgery, and laser ablation. According to ACoS rules, dilation and curettage is not recorded as local tumor destruction or excision.27 Special codes describe the absence of surgical treatment, unknown surgical procedures, and lack of knowledge of whether surgery was performed.

For vaginal and vulvar carcinomas, the surgery data item recorded whether local disease control was attempted by tumor destruction techniques that did not result in a pathologic specimen (eg, laser, fluorouracil cream), by wide local excision, or by organ removal (ie, vaginectomy, vulvectomy). For all cancer sites of interest, treatment surveillance data allowed for the identification of patients who received radiation therapy and provided the categorization of irradiation procedures (ie, external beam vs brachy-therapy).

Classification and Analysis

The tumors that were included in this analysis were classified according to the American Joint Committee on Cancer (AJCC) staging rules,28 which are identical to the widely used International Federation of Gynecology and Obstetrics (FIGO) staging system but differ slightly from the SEER Summary Staging system. We stratified tumors on the basis of the clinically relevant AJCC/FIGO stage to compare the treatment of cancer cases with similar disease progression at diagnosis. The analysis of cervical tumors was performed by FIGO group stage IA, IB, IIA, IIB, III, and IV. Staging information at the finest level of granularity (FIGO stages IA1, IA2, IB1, and IB2) was available for cases diagnosed in year 2004 only.

Demographic information (ie, race, ethnicity, age, and marital status at diagnosis) was collected and reported according to SEER standards.29 Cases with missing information on marital status (n = 314), cases of unknown/other race (n = 79), and cases of American Indian or Alaskan Native race (n = 34) were not included in the analysis of hysterectomy performed to treat cervical carcinoma.

We calculated the proportion of cervical carcinomas by treatment status (eg, treatment vs no treatment vs unknown treatment), AJCC stage (eg, stage I vs stages II-III vs stage IV), and tumor cell histology (eg, ‘squamous carcinoma/carcinoma, not otherwise specified’ vs ‘nonsquamous carcinoma’). We combined cases with missing information for either surgical treatment or radiation therapy into 1 group. Cases with disease stages II and III were grouped into 1 category, because preliminary analysis indicated that there was no significant variation between these stage groups with regard to no treatment or missing treatment data patterns. Because of small numbers and similar treatment characteristics, adenocarcinomas were combined with other nonsquamous carcinomas. A small number of carcinomas with ‘surgery, not otherwise specified’ (n = 84) were reclassified to the hysterectomy group based on observed surgery distribution among cases with similar tumor characteristics. We analyzed the distribution of cervical cancer cases that received treatment by surgery/radiotherapy combination, AJCC stage, and tumor histology. Similarly, we examined the treatment of vaginal and vulvar cancer cases by tumor stage (stage 0 vs stages I-III vs stage IV).

For AJCC stage I cervical carcinomas, we determined the proportion of women who underwent hysterectomy by age category (ages 20-29 years, 30-44 years, 45-64 years, ≥65 years), race (white, black, and Asian/Pacific Islander), ethnicity (non-Hispanic vs Hispanic), marital status, and tumor histology. Next, we used Poisson regression modeling (ie, SAS GENMOD Procedure30) to estimate the likelihood of undergoing hysterectomy by age, race/ethnicity, marital status, and tumor histology compared with the baseline category of black women ages 20 to 29 years who were diagnosed with cervical squamous carcinoma while adjusting for participating registry. Finally, we used the SAS GENMOD Procedure and the Joinpoint Regression Program31 to test whether there was a trend in the frequency of hysterectomy for cervical carcinomas between 1992 and 2004 after adjusting for age and histology, stratified by the race/ethnicity combination. Because of small numbers (n = 27), Hispanic black women were classified as black in this analysis. The SEER Program had converted earlier treatment codes to the current FORDS codes, enabling us to use data going back to 1992 for the time trend analysis.

RESULTS

Table 1 shows the treatment distribution of cervical carcinomas by histology type and AJCC stage grouping. Approximately 94% of women diagnosed with stages I through III squamous cervical carcinomas received surgery and/or radiation therapy; however, a much lower percentage of women (77.9%) with stage IV disease received these treatments. A similar treatment distribution also was observed for women with nonsquamous cervical carcinomas.

Table 1. Treatment Status for Invasive Cervical Carcinomas by Known American Joint Committee on Cancer/International Federation of Gynecology and Obstetrics Stage: Combined Surveillance, Epidemiology, and End Results Registries, 2000-2004*
 Squamous Carcinoma/Carcinoma, NOSNonsquamous Carcinoma
 Stage IStage II-IIIStage IVStage IStage II-IIIStage IV
Treatment StatusCount%Count%Count%Count%Count%Count%
  • NOS indicates not otherwise specified; RT, radiation therapy.

  • *

    Source: Surveillance, Epidemiology, and End Results (SEER) Program: Incidence—SEER 17 Registries Limited-Use, National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Cancer Statistics Branch (released April 2007, based on the November 2006 submission). Data are from 17 population-based cancer registries that participate in SEER and meet high-quality data criteria (San Francisco-Oakland Standard Metropolitan Statistical Area, Connecticut, Metropolitan Detroit, Hawaii, Iowa, New Mexico, Seattle-Puget Sound, Utah, Alaska Natives, Metropolitan Atlanta, San Jose-Monterey, Los Angeles, Rural Georgia, Greater California, Kentucky, Louisiana, and New Jersey). These registries cover approximately 27% of the U.S. population.

Surgery was performed and/or RT was administered475194.2331493.896077.9201495.783694.035375.6
Neither surgery nor RT was administered1703.41464.123419.0472.2303.49821.0
Unknown whether surgery and/or RT were administered1242.5742.1394.2442.1232.6163.3
Total5045 3534 1233 2105 889 467 

For those who did receive treatment for cervical carcinomas, the treatment modality varied by tumor stage. Women with less advanced disease (stage IA and IB) were more likely to undergo surgical treatment, as expected. Table 2 shows that 73.4% of patients with stage IA cervical carcinoma and 78.3% of patients with stage IB cervical carcinoma underwent hysterectomy (with or without adjuvant radiation therapy). Overall, <6% of patients with stage IA cervical carcinoma were treated with radiation. This is significantly different from the proportion we observed among stage IB patients (approximately 40%). The distribution of treatment recorded for patients diagnosed at stage IIA and III was similar to some extent: Approximately 35% of patients underwent hysterectomy, and 28% received a combination of external pelvic irradiation and intracavitary radiotherapy. The treatment distribution for patients with stage IIB disease differed from the treatment distribution both for patients with stage IIA disease and for patients with III disease; patients with stage IIB cervical carcinoma were less likely to undergo hysterectomy (18.2%) and more likely to receive a combination of external beam and intracavitary radiation therapy (42.7%). Patients with late-stage (stage IV) cervical carcinoma received radiation more frequently (>92%); however, approximately 29% of women in this category also underwent some form of cancer-directed surgery.

Table 2. Treatment Modality Distribution for Invasive Cervical Carcinomas by American Joint Committee on Cancer/International Federation of Gynecology and Obstetrics Stage: Combined Surveillance, Epidemiology, and End Results Registries, 2000-2004*
 Stage IAStage IBStage I, NOSStage IIAStage IIBStage IIIStage IV
Treatment ModalityCount%Count%Count%Count%Count%Count%Count%
  • NOS indicates not otherwise specified; RT, radiotherapy.

  • *

    Source: Surveillance, Epidemiology, and End Results (SEER) Program: Incidence—SEER 17 Registries Limited-Use, National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Cancer Statistics Branch (released April 2007, based on the November 2006 submission). Data are from 17 population-based cancer registries that participate in SEER and meet high-quality data criteria (San Francisco-Oakland Standard Metropolitan Statistical Area, Connecticut, Metropolitan Detroit, Hawaii, Iowa, New Mexico, Seattle-Puget Sound, Utah, Alaska Natives, Metropolitan Atlanta, San Jose-Monterey, Los Angeles, Rural Georgia, Greater California, Kentucky, Louisiana, and New Jersey).

  • Counts include 13 patients who underwent surgery, NOS.

  • Counts include 71 patients who underwent surgery, NOS.

Local excision (any procedure)68823.51023.28412.761.390.7220.9151.1
Local excision and RT361.21454.6467.05110.61108.41275.4715.4
Hysterectomy without adjuvant206170.3179356.428042.46212.9352.71526.4806.1
Hysterectomy with adjuvant903.169621.911016.79920.720315.572630.821116.1
Beam RT alone (pelvic irradiation)160.51554.9548.210822.533625.659925.463548.4
RT (beam and intracavitary)130.42568.17110.813428.056042.766328.127220.7
Other combination of surgery and RT240.8300.9152.3194.0594.5703.0292.2
Total2928 3771 660 479 1312 2359 1313 

The analysis of a subset of patients diagnosed in the year 2004 (data not shown in tables) indicated that local excision was the treatment choice for 24.3% of women with stage IA1 disease and for 27.2% of women with stage IA2 disease. All other stage groups (stages IB1, IB2, IIA, IIB, III, and IV) included small proportions of patients who underwent local tumor excision (typically between 1% and 5%); between 2% and 12% of patients in these stage groups who received a combination of local excision followed by adjuvant pelvic irradiation. Hysterectomy, either alone or in combination with pelvic irradiation, was undergone by the majority of patients who were diagnosed at stage IA1, IA2, IB1, or IB2. In addition, the proportion of patients who received some form of radiation (external beam and/or intracavitary) varied dramatically, from 3% among patients with stage IA1 disease to 80% among patients with stage IB2 disease (data not shown in tables).

Because in situ (stage 0) carcinomas of the vagina and vulva are reportable to the SEER Program, cases diagnosed with such tumors were included in the analyses. Approximately 73.4% of women who were diagnosed with stage 0 vaginal carcinomas and 84.8% of women who were diagnosed with stage 0 vulvar carcinomas underwent surgery and/or received radiation (Table 3). Compared with women who had stage 0 disease, treatment was more frequent among women who were diagnosed at stages I through III (90.9% for vaginal carcinomas and 95.1% for vulvar carcinomas) and slightly less frequent among women who were diagnosed at stage IV (72% for vaginal carcinomas and 77.4% for vulvar carcinomas). Among patients who underwent surgery and/or received radiation therapy, the treatment modality distribution also was related to the disease stage (Table 4). For patients with stage 0 disease, the most common procedure was wide local excision (53.8% for vaginal carcinomas and 63% for vulvar carcinomas), followed by local tumor destruction for carcinomas of the vagina (26.3%), and vulvectomy without adjuvant therapy for carcinomas of the vulva (30.5%). For women who had vaginal carcinomas in stage I through III, brachytherapy alone or in combination with external-beam therapy together accounted for approximately 40.1% of treatments. However, vulvectomy without adjuvant therapy (58.2%) was the most common treatment combination used to treat stage I through III vulvar carcinomas. External-beam irradiation alone was more likely to be the treatment selection of women with either vaginal (67.4%) or vulvar (45.8%) carcinomas at stage IV.

Table 3. Treatment Status for Vaginal and Vulvar Carcinomas by Known American Joint Committee on Cancer Stage: Combined Surveillance, Epidemiology, and End Results Registries, 2000-2004*
 Carcinomas of the VaginaCarcinomas of the Vulva
 Stage 0Stage I-IIIStage IVStage 0Stage I-IIIStage IV
Treatment StatusCount%Count%Count%Count%Count%Count%
  • RT indicates radiotherapy.

  • *

    Source: Surveillance, Epidemiology, and End Results (SEER) Program: Incidence—SEER 17 Registries Limited-Use, National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Cancer Statistics Branch (released April 2007, based on the November 2006 submission). Data are from 17 population-based cancer registries that participate in SEER and meet high-quality data criteria (San Francisco-Oakland Standard Metropolitan Statistical Area, Connecticut, Metropolitan Detroit, Hawaii, Iowa, New Mexico, Seattle-Puget Sound, Utah, Alaska Natives, Metropolitan Atlanta, San Jose-Monterey, Los Angeles, Rural Georgia, Greater California, Kentucky, Louisiana, and New Jersey).

Surgery was performed and/or RT was administered73173.446190.99572.0478884.8159595.112077.4
Neither surgery nor RT was administered25025.1316.13526.572612.9472.82717.4
Unknown whether surgery and/or RT was administered151.5153.021.51352.4352.185.2
Total996 507 132 5649 1677 155 
Table 4. Treatment Modality Distribution for Vaginal and Vulvar Carcinomas by Known American Joint Committee on Cancer/International Federation of Gynecology and Obstetrics Stage: Combined Surveillance, Epidemiology, and End Results Registries, 2000-2004*
 Carcinomas of the VaginaCarcinomas of the Vulva
 Stage 0Stage I-IIIStage IVStage 0Stage I-IIIStage IV
Treatment ModalityCount%Count%Count%Count%Count%Count%
  • *

    Source: Surveillance, Epidemiology, and End Results (SEER) Program: Incidence—SEER 17 Registries Limited-Use, National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Cancer Statistics Branch (released April 2007, based on the November 2006 submission). Data are from 17 population-based cancer registries that participate in SEER and meet high-quality data criteria (San Francisco-Oakland Standard Metropolitan Statistical Area, Connecticut, Metropolitan Detroit, Hawaii, Iowa, New Mexico, Seattle-Puget Sound, Utah, Alaska Natives, Metropolitan Atlanta, San Jose-Monterey, Los Angeles, Rural Georgia, Greater California, Kentucky, Louisiana, and New Jersey).

Local tumor destruction (laser, fluorouracil cream)19226.300.000.02996.220.100.0
Wide local excision (with/without grafting)39353.8306.555.3301763.023614.854.2
Vaginectomy/vulvectomy without adjuvant therapy13818.94610.033.2146230.592858.21915.8
Vaginectomy/vulvectomy with adjuvant therapy00.06614.31111.620.025415.93226.7
External-beam irradiation alone20.313429.16467.430.11247.85545.8
Other, including combined therapies60.818540.11212.650.1513.297.5
Total731 461 95 4788 1595 120 

Among patients with stage I cervical carcinoma (Table 5), age, race, marital status, and tumor histology all were found to be associated significantly with hysterectomy. Specifically, the likelihood of undergoing hysterectomy was higher for women ages 30 to 64 years than for women ages 20 to 29 years, who had a likelihood of undergoing hysterectomy that was no different from that for women aged ≥65 years. White women and Asian/Pacific Islander women were more likely to undergo hysterectomy than black women. Hispanic ethnicity was not associated significantly with the likelihood of undergoing hysterectomy when the Poisson model was adjusted for other factors (age, race, marital status, tumor histology, and participating registry). The likelihood of undergoing hysterectomy was higher for married women than for single women. In addition, women with nonsquamous carcinomas had a higher likelihood of undergoing hysterectomy than women with squamous carcinomas.

Table 5. Crude and Adjusted Likelihood of Hysterectomy for American Joint Committee on Cancer/International Federation of Gynecology and Obstetrics Stage I Cervical Carcinomas by Selected Demographic and Tumor Characteristics: Combined Surveillance, Epidemiology, and End Results Registries, 2000-2004*
VariableCount% HysterectomyCrude RR (95% CI)Adjusted RR (95% CI)
  • RR indicates relative risk; 95% CI, 95% confidence interval; NOS, not otherwise specified.

  • *

    Source: Surveillance, Epidemiology, and End Results (SEER) Program: Incidence—SEER 17 Registries Limited-Use, National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Cancer Statistics Branch (released April 2007, based on the November 2006 submission). Data are from 16 population-based cancer registries that participate in SEER and meet high-quality data criteria (San Francisco-Oakland Standard Metropolitan Statistical Area, Connecticut, Metropolitan Detroit, Hawaii, Iowa, New Mexico, Seattle-Puget Sound, Utah, Metropolitan Atlanta, San Jose-Monterey, Los Angeles, Rural Georgia, Greater California, Kentucky, Louisiana, and New Jersey).

  • Crude RR estimated from a simple Poisson regression model.

  • Adjusted RR estimated from a multivariate Poisson regression model that included demographic characteristics, tumor histology, and participating registry.

  • §

    Counts exclude 113 cases with American Indian-Alaska Native/other /unknown race (63.7% underwent hysterectomy).

  • Counts exclude 314 cases with unknown marital status (60.5% underwent hysterectomy).

Age category, y    
 20-2958354.91.01.0
 30-44316078.01.4 (1.3-1.5)1.4 (1.2-1.5)
 45-64231378.21.4 (1.3-1.5)1.4 (1.2-1.5)
 ≥6571759.11.1 (1.0-1.2)1.0 (0.9-1.2)
Race§    
 Black78359.91.01.0
 White530975.61.3 (1.2-1.3)1.1 (1.0-1.3)
 Asian/Pacific Islander56881.01.4 (1.3-1.5)1.2 (1.0-1.4)
Ethnicity    
 Non-Hispanic518873.41.01.0
 Hispanic158576.21.0 (1.0-1.1)1.0 (0.9-1.1)
Marital status at diagnosis    
 Single165366.41.01.0
 Married348079.91.2 (1.2-1.3)1.1 (1.1-1.2)
 Separated/divorced/widowed132671.51.1 (1.0-1.1)1.1 (1.0-1.2)
Tumor histology    
 Squamous/carcinoma NOS475670.71.01.0
 Nonsquamous201781.21.2 (1.1-1.2)1.1 (1.1-1.2)

Figure 1 illustrates the trend of hysterectomy procedures performed per 100 patients with stage I cervical cancer, by race and ethnicity, over a 13-year observation period. After adjusting for participating registry, age, and tumor histology, women in the Asian/Pacific Islander group had underwent highest proportion of hysterectomy procedures (ranging from 85% in 1992 to 80% in 2004), followed by non-Hispanic white women, and Hispanic white women. Black women were less likely to undergo hysterectomy (approximately 60%) than nonblack women. During the last 13 years, a decreasing trend of hysterectomy was observed for non-Hispanic white women (P = .02) and Asian/Pacific Islander women (P > .05), whereas there was a very slight increase in hysterectomies among white women of Hispanic origin (P > .05). Black women did not experience much change in the frequency of hysterectomies between 1992 and 2004.

Figure 1.

Hysterectomy procedures per 100 cases diagnosed with American Joint Committee on Cancer/International Federation of Gynecology and Obstetrics stage I cervical carcinoma, by race and ethnicity, adjusted for age and tumor histology for the Surveillance, Epidemiology, and End Results (SEER)-13 registries combined areas, 1992 through 2004. API indicates Asian/Pacific islander. Source: SEER Program: Incidence—SEER 13 Registries Limited-Use, National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Cancer Statistics Branch (released April 2007, based on the November 2006 submission). Data are from 12 population-based cancer registries that participate in SEER and meet high-quality data criteria (the San Francisco-Oakland Standard Metropolitan Statistical Area, Connecticut, Metropolitan Detroit, Hawaii, Iowa, New Mexico, Seattle-Puget Sound, Utah, Metropolitan Atlanta, San Jose-Monterey, Los Angeles, and Rural Georgia).

DISCUSSION

In this report, we provide data on the distribution of treatment for HPV-associated gynecologic cancers before the implementation of HPV-immunization programs in the US. We observed that, as expected, the type of treatment was associated with tumor histology and stage at diagnosis. Specifically, we observed that women with early-stage cancer (stages IA and IB) were more likely to undergo surgery, whereas those diagnosed at stages IIA, IIB, III, and IV tended to receive radiation therapy. There were no major differences in the distribution of treatment for stage IA1 versus stage IA2, but patients who were diagnosed at stage IB2 were significantly more likely to receive radiation therapy than any other stage I subgroup. Women with nonsquamous cervical carcinomas were more likely to undergo hysterectomy than to receive pelvic irradiation. The analysis of surgical treatment for stage I cervical cancer suggests that there was significant variation in hysterectomy use by age group, race, marital status, and tumor histology. Among those with stage I cervical carcinoma, black women were more likely than white women to be treated with LEEP and adjuvant radiotherapy rather than hysterectomy. Over the past 13 years, there has been a gradual downtrend in the use of hysterectomy, although the use of the procedure increased slightly among Hispanic white women. Black women were approximately 25% less likely than nonblack women to undergo hysterectomy, and the gap has not narrowed over time.

Nonsquamous carcinomas of the cervix tend to be associated with higher case fatality relative to squamous cell carcinomas.32 This association may explain why, in our study, women with nonsquamous tumors were more likely to receive aggressive treatment (hysterectomy), independent of disease stage. Alternatively, because approximately 90% of nonsquamous cervical cancers with known subsite were localized to the endocervix (data not shown), the decision for these women to undergo hysterectomy may have been because of the endocervical origin and the likelihood of disease progression to the uterine corpus. Endocervical cancers are more likely than cancers that arise in other subsites to have nonsquamous histology; however, because nearly 90% of cervical cancers were reported without a specific subsite, we were not able to analyze the frequency of hysterectomy based on either the site of origin alone or on the combination of the site and histology. The National Comprehensive Cancer Networks's Clinical Practice Guidelines for cervical cancer do not differentiate treatment recommendations according to either tumor histology or cervical subsite.33

Another major determinant of hysterectomy treatment was the age at diagnosis. Hysterectomy was less frequently the first choice of treatment among young women (ages 20-29 years), possibly in an effort to preserve fertility.34 The use of hysterectomy for the treatment of gynecologic malignancies was highest for women ages 30 to 64 years. Our finding is consistent with the pattern recently reported by Babalola et al in Minnesota35 and with a multicenter, multinational case series analyzed by Quinn et al.16 Hysterectomy has the advantage of removing the risk of recurrent cervical disease.34 In our study, hysterectomy was the method of choice for early cervical cancer in the majority of patients. The higher risk of morbidity associated with removal of the uterus most likely limits the use of hysterectomy in women aged ≥65 years.36

Poor Papanicolaou (Pap) test screening practices37, 38 and overuse of hysterectomy39 for benign conditions have been documented both in black women and Hispanic women. We observed no positive association between hysterectomy and black race or Hispanic ethnicity for women who were diagnosed with stage I cervical cancer. Specifically, the trends of hysterectomy use point toward a slight increase among Hispanic white women and a steady decrease among non-Hispanic white and Asian/Pacific Islander women. The lower rate of hysterectomy procedures among black women than among nonblack women remained. This may be attributable to any combination of previously reported findings concerning black women's health: higher rates of posthysterectomy complications, higher comorbidity, the inappropriate use of hysterectomy, misperception of cancer fatalism, and lower hysterectomy rates among noninsured/Medicaid patients.40–43

By design, the SEER Program comprises a large proportion of racial and ethnic minority groups; therefore, the treatment distribution we report in this article may be biased toward patterns observed in minority groups—whereas Asians/Pacific Islanders tend to receive more aggressive treatment, black women seem to receive less aggressive treatment. The proportion of women who did not undergo surgery or receive radiation therapy was low, although it tended to be somewhat higher for those with unknown tumor stage. Our results demonstrate that women with stage 0 vaginal cancer were less likely than women with stage 0 vulvar cancer to undergo surgery or receive radiation. A noticeable proportion of vulvar and vaginal cancer cases were reported by independent pathology laboratories or private physician offices (data not shown). Because it is likely that procedures such as excisional biopsies performed in physicians' offices are not documented or reported as frequently as those performed in a hospital setting, this may explain in part why the proportion of untreated women was relatively high.

The trends and patterns we present in this report, in particular those illustrated in Table 5 and Figure 1, were not adjusted for comorbidities or other factors that may have played a role in the selection of treatment. To the extent that these factors were associated with a particular demographic group (ie, black race), they may have biased the results presented. In addition, the standard and quality of care are expected to vary across stage groups. To address these prospective limitations, we carefully restricted the analysis to FIGO stage I cervical tumors reported by 12 central cancer registries, and we adjusted for differences in reporting patterns as well as for variation in the distribution of histology, age, and other demographic factors. Although admittedly it is less than perfect, the adjustment reduces the likelihood of bias associated with geographic patterns of care and socioeconomic disparities.

Notwithstanding the limitations, the findings in this study may have important cost implications. Substantial treatment costs of female genital carcinomas have been reported. For example, in 2003, Fetters et al reported unit costs of the following treatment procedures: local tumor destruction using 5-fluorouracil cream (average cost, $70; range: $53-88), laser ablation (average cost, $951; range, $713-4440), vaginectomy (average cost, $23,000; range, $17,125-28,750), and radiation therapy (average cost, $18,000; range, $13,500-22,500).44 These estimated unit costs can be used to quantify the magnitude of the direct medical treatment costs for each cancer site presented in this study. For instance, the direct medical cost of treating cervical cancer in 2004 has been estimated at $1.7 billion.45 The direct medical costs of treating vaginal and vulvar cancers have not been reported; however, direct medical treatment costs of HPV-associated infections, which include vaginal and vulvar cancers as well as cervical cancer, have been estimated to range from $2.3 billion to $6 billion per year.46–48 At the aggregate level, the direct medical cost of treating all cancer in 2004 was estimated at $72.1 billion.45 These treatment costs are significant, and they underscore the need for more effective intervention strategies to reduce the health and economic cost burden to individuals who are diagnosed with these HPV-associated cancers, their families, and society as a whole.

Currently, there is consensus that the frontier in HPV-associated cancers is in the potential use of prophylactic vaccines to control HPV infection and of therapeutic vaccines to treat genital cancers. The baseline treatment data reported in this article provide information that can be used to quantify the distribution of costs associated with treatment of these HPV-associated cancers. This information also may aid health policy researchers in comparing the financial and human costs associated with HPV-associated cancer prevention and treatment before and after the widespread use of HPV vaccination.

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