Cervical cancer is still an incredibly devastating cancer, especially when it is late-stage disease. It is important that women still recognize the need to be screened, the fact that you can catch it early, and the importance of being referred to a gynecologic oncologist at the time of diagnosis to receive appropriate treatment.— Anna Beavis, MD, MPH
Cervical cancer mortality rates were significantly higher, particularly among black women, when national data were corrected to exclude women who have had hysterectomies. For black women, the cervical cancer mortality rate rose from 5.7 to 10.1 per 100,000 when corrected for hysterectomy, an increase of 77%. For white women, the cervical cancer mortality rate rose from 3.2 to 4.7 per 100,000 when corrected for hysterectomy, an increase of 47%. “Without the correction, the disparity in mortality between races was underestimated by 44%,” the authors of the study revealing the disparity wrote in Cancer.1
“Age-specific cervical cancer mortality rates increased with age for all races, and corrected and uncorrected rates did not plateau at any point,” the authors noted. “Corrected rates were highest for black women who were 85 years and older.”
Aware of the Disparity
The authors concluded: “Given that both older age and black race have been shown to be independent predictors of inadequate treatment after diagnosis, clinicians must be aware of the disparity to help ensure equal treatment in the future.”
Publication of the study and reporting by national media, including network news, USA Today, Time, and New York Magazine, is already raising awareness of the disparity. “The press coverage was more extensive than I had anticipated, but I am very pleased with the attention the study has received from both the public and the gynecology and oncology communities,” the study’s lead author, Anna Beavis, MD, MPH, said in an interview with The ASCO Post. Dr. Beavis is Clinical Fellow with the Kelly Gynecologic Oncology Service, Johns Hopkins Hospital, Baltimore.
Commenting on the study for the PBS NewsHour,2 Jennifer Caudle, DO, said she was “speaking as a family physician, but also as a black woman,” when she wrote an op-ed piece for CNN, noting the existence of health disparities “is not a new phenomenon, and it is not unique to cervical cancer, but it still takes my breath away that racial disparities in health continue to be so robust.”3 A family medicine physician and Assistant Professor, Department of Family Medicine, Rowan University-School of Osteopathic Medicine, Philadelphia, Dr. Caudle said that cervical cancer mortality is “something we have to keep talking about.”
Dr. Beavis was pleased that the study has fostered that conversation. “I think it is very important, because we have reduced rates of cervical cancer with the Papanicolaou smear, and in the next several decades, we will likely see a reduction from the human papillomavirus (HPV) vaccine as well.” But cervical cancer, she continued, “is still an incredibly devastating cancer, especially when it is late-stage disease. It is important that women still recognize the need to be screened, the fact that you can catch it early, and the importance of being referred to a gynecologic oncologist at the time of diagnosis to receive appropriate treatment.”
The authors wrote: “Prior studies have shown that a failure to account for the prevalence of hysterectomy has resulted in an underestimation of cervical cancer incidence rates because women who have had their cervix surgically removed are inappropriately retained in the population-at-risk denominator. This underestimation had the most profound effect in black women because they have the highest prevalence of hysterectomy.”
Other studies have shown that black women are more likely than white women to have had hysterectomies, and may have the procedure at younger ages, possibly because they are more susceptible to fibroid tumors. “Other studies have shown that black women are just more likely to have fibroids, more likely to have larger fibroids, and may be more symptomatic at a younger age,” Dr. Beavis said.
Other studies have looked at cervical cancer incidence, but this was the first study to correct for hysterectomy in determining cervical cancer mortality, Dr. Beavis noted.
Comparing the corrected mortality rates for black and white women in the United States to global mortality rates “helps to put the significance of the racial disparity into perspective,” according to the study report. The corrected mortality for white women (3.4 per 100,000) was equivalent to the GLOBOCAN estimated rate of 3.3 per 100,000 for women in Europe, Australia/New Zealand, and Japan. “However, the corrected estimate for black women living in the United States of 10.1 per 100,000 is on par with the GLOBOCAN estimate of 9.8 per 100,000 for less-developed nations (ie, all of Africa, Asia [excluding Japan], Latin America, and the Caribbean),” the authors wrote, and “as high as those seen in sub-Saharan Africa.”
According to the American Cancer Society, there will be an estimated 12,820 new cervical cancer cases in the United States in 2017 and an estimated 4,210 deaths.
Implications for Older Women
The study found that “age-specific cervical cancer mortality rates increased with age” and “did not plateau at any point.” Current screening guidelines from the U.S. Preventive Services Task Force (USPSTF), however, recommend against screening for cervical cancer in “women older than age 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer.”4 (According to the USPSTF website, an updated recommendation statement is in development, scheduled for release in 2018.)
“It is beyond the scope of this study to say that we should change any screening recommendations, but I do think that it is important to recognize that older women are still at risk and to make sure women are appropriately screened within the guidelines,” Dr. Beavis said.
“A couple of national studies demonstrated that screening rates are basically the same between races, but that it is potentially the follow-up from screening where things fall short [among black women],” Dr. Beavis added. If we could identify upfront which women are at risk for not finishing therapy, delaying surgery, or taking a long time to complete radiation, we could institute interventions, like a navigator, to try to ensure therapy is completed in a timely manner.”
Effects of Screening and HPV Vaccine
Despite the disparity in cervical cancer mortality between black and white women, “a trend analysis of the corrected cervical cancer mortality data does suggest that the mortality gap may in fact be closing, because black women have a larger annual percentage decrease in mortality compared with white women after correction.” Because cervical cancer is a slow-growing cancer, the more recent decrease in mortality “reflects changes that happened likely at least 10 years ago, probably over the past 2 decades.” It is still too early to ascertain the effects of the HPV vaccine, she said.
Despite efficacy approaching 100%, a survey in 2014 showed that only 40% of girls aged 13 to 17 years in the United States had completed the recommended 3 doses of the vaccine, and 60% had received just 1 dose,5 according to an editorial accompanying the study report.6 (The newer monovalent vaccine requires just 2 doses for boys and girls between the ages of 9 and 14.) The editorial was written by Heather J. Dalton, MD, of Arizona Oncology, and John H. Farley, MD, of Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, Phoenix.6
Provider Role in Vaccine Use
Why hasn’t the vaccine been more widely used? “Reviewing the literature on this, it seems to be a combination of lack of recognition that the vaccine is necessary and providers not recommending the vaccine with the same enthusiasm that they recommend other vaccines,” Dr. Beavis said. “There are also data to suggest that who recommends the vaccine changes vaccination rates.” For example, she said, a pediatrician’s recommendation might lead to higher rates of vaccination among patients than advice from a family physician.
“HPV vaccination is expected to
decrease disparities across races, but this requires access to adequate preventive care. Much like screening for cervical dysplasia, programs that increase community and provider knowledge about HPV vaccination and facilitate access to preventive care and vaccination are essential,” Dr. Dalton and Dr. Farley wrote in their editorial.
Resistance from parents questioning the need for vaccination in young people not thought to be sexually active “probably is decreasing as a factor, as people recognize that regardless, this is an incredibly common virus,” Dr. Beavis said. “Yes, it is due to a sexually transmitted infection, but it can be passed without penetrative intercourse, and the reality is that most people will be infected with HPV at some point in their lifetime. It causes a cancer that we can prevent, and so why shouldn’t we?”
Dr. Beavis reported that she recently performed an analysis of the parent-reported reasons for lack of initiation of HPV immunization in teenagers and will be presenting the data at the upcoming annual meeting of the Society of Gynecologic Oncology.
Cause of Disparity ‘Elusive’
The cause of the disparity in cervical cancer mortality “is elusive but is felt to be multifactorial, with factors ranging from differences in tumor histology and stage to differences in access to screening programs and cultural differences,” according to the editorial accompanying the study report.
“A differential distribution of histologic subtypes by age and race may explain some of the differences in mortality rates: Rates of adenocarcinoma in black women increase with increasing age, whereas they plateau at age 35 in white women,” the study authors noted. As noted in the editorial, “although the incidence of squamous cell carcinoma has decreased, this trend has not been mirrored in cases of adenocarcinoma. Compared with a squamous histology, adenocarcinoma is associated with a worse prognosis and worse survival for both early- and late-stage disease.”
“Regular Pap screenings can help detect precancerous lesions but tend to be better at picking up squamous cell lesions than glandular lesions. She also pointed out that the HPV vaccine is effective against both squamous cell carcinoma and adenocarcinoma, “and so hopefully, that increased amount of adenocarcinoma can be somewhat prevented by uptake of the HPV vaccine.”
Access to Screening and Treatment
“Access to cervical cancer screening has been investigated as a significant contributor to racial disparities,” according to the editorial accompanying the study report. “Data suggest that women at high risk for cervical cancer either do not have adequate access to preventive services or choose not to use preventive services. Cultural differences, including mistrust of the health-care system, may play a role. In these high-risk populations, community-based interventions offer potential solutions because they may better cater to cultural beliefs and attitudes. Other studies have found equivalent cervical screening rates in black and white women.”
An evaluation of Maryland Cancer Registry data7 cited in the study report found that black women were “less likely to get appropriate treatment or complete treatment upfront,” Dr. Beavis noted. “That has been confirmed in national data, in the [Surveillance, Epidemiology, and End results (SEER)] database as well,”8 she added. The finding from the SEER data “is concordant with the current study’s finding that the oldest black women have the highest cervical cancer mortality rates and supports research to gain an understanding of why this unique population receives differential treatment for the same disease,” Dr. Beavis and her coauthors wrote.
Studies show that black women diagnosed with cervical cancer “are less likely to have surgery,” Dr. Beavis said. “We also know that black women present at a later stage for cervical cancer, which could be due to not wanting to come in, even if they are having symptoms, for example. But even if we look at stage for stage, white vs black, black women are still less likely to have surgery.”
Social Determinants of Health
The study report concludes that future research should “focus on overcoming factors that contribute to this mortality gap” and “on determining why black women and older women receive different and inadequate treatment for the same disease.”
“Our research needs to focus on why there isn’t the same treatment for black women as white women, and I think we will have to delve into the social determinants of health,” Dr. Beavis said. “A lot of times cervical cancer treatment involves chemotherapy and radiation, which requires a lot of social support, transportation, and related factors.”
“I have initiated a study looking specifically at Johns Hopkins as a single institution, because I think getting down to that granular data is very difficult to do in these large databases,” Dr. Beavis said. “So while we hope to collect data from other institutions as well, initially I am looking at our data, because we can actually look at day-by-day reasons why women aren’t either completing radiation on time or getting their recommended radiation treatment.” The study will also consider other forms of treatment for cervical cancer.
Combining Multiple Databases
To estimate cervical cancer mortality rates corrected for hysterectomy, the investigators first estimated the age-, race-, year- and state-stratified hysterectomy prevalence from national survey data and then used those estimates to correct the denominator of equivalently stratified cervical cancer mortality estimates. Those estimates came from the SEER database.
“With this type of study, you have to combine multiple databases,” Dr. Beavis explained. “We actually had to obtain death records from the National Center for Health Statistics, which is not a publicly available data set, and then combine it with another national study that estimates hysterectomy prevalence. Those studies are typically not combined, and we had to methodologically put them together,” Dr. Beavis explained. “Moving forward, it’s important to continue to correct cervical cancer rates for hysterectomy and look at trends over time,” she said. ■
Disclosure: Dr. Beavis reported no potential conflicts of interest.
4. U.S. Preventive Services Task Force: Cervical cancer: Screening. Available at www.uspreventiveservicestaskforce.org. March 2012 (update in progress).
5. Reagan-Steiner S, Yankey D, Jeyarajah J, et al: National, regional, state, and selected local area vaccination coverage among adolescents aged 13–17 years—United States, 2014. MMWR Morb Mortal Wkly Rep 64:784-792, 2015.