Cervical cancer death rates higher among older and black women

A woman’s risk of dying of cervical cancer is higher than long believed, particularly among older and black women, new Johns Hopkins Bloomberg School of Public Health-led research suggests.

The researchers found that black women in the United States are dying from cervical cancer at a rate 77 percent higher than previously thought while white women are dying at a rate 47 percent higher. The new figures reflect a change in how mortality rates are calculated. By excluding women who have had hysterectomies, which typically involves the removal of the cervix and therefore reduces the risk of developing cervical cancer to zero, the researchers say these data paint a more accurate picture of who is getting cervical cancer – and can be used to better understand how to prevent it.

Meanwhile, many of those who are dying are over the age of 65, a cutoff point where guidelines no longer recommend women with cervixes be regularly screened for cervical cancer. With routine screening, cervical cancer is preventable. In the United States, there are 12,000 cases of cervical cancer each year and around 4,000 deaths.

The findings, published Jan. 23 in the journal Cancer, highlight the need to understand the risks associated with cervical cancer in older and black women and determine both the best screening and treatment options for these women.

This is a preventable disease and women should not be getting it, let alone dying from it,” says study leader Anne F. Rositch, PhD, MSPH, an assistant professor in the Department of Epidemiology at the Bloomberg School. “Since the goal of a screening program is to ultimately reduce mortality from cervical cancer, then you must have accurate estimates within the population targeted by those programs — adult women with a cervix. These findings motivate us to better understand why, despite the wide availability of screening and treatment, older and black women are still dying from cervical cancer at such high rates in the United States.”

Excluding women with a history of a hysterectomy, something that has not been done in previous calculations, makes a sizable difference since one in five women in the United States have had a hysterectomy, with the number slightly higher in black women than white women. Current guidelines do not recommend cervical cancer screening after the age of 65, since it was believed that older women were at much less risk. These new findings suggest the risk remains – and even increases – in older women.

These data tell us that as long as a woman retains her cervix, it is important that she continue to obtain recommended screening for cervical cancer since the risk of death from the disease remains significant well into older age,” Rositch says.

To produce these national mortality rates, the researchers analyzed cervical cancer mortality rates using national death certificate data from the National Center for Health Statistics and from the Surveillance, Epidemiology, and End Results (SEER) national cancer registries and then removed the proportion of women who reported a hysterectomy, a number obtained from a national survey.

The rate of cervical cancer mortality among black women over the age of 20 was 5.7 per 100,000 each year and 3.2 per 100,000 each year in white women. The rate in black women jumped to 10.1 per 100,000 per year when corrected for hysterectomy, a rate similar to less developed nations, and to 4.7 per 100,000 per year in white women. Black women are more likely to have hysterectomies, and at younger ages, compared to white women, largely because black women are more susceptible to fibroids — benign masses in the uterus — which can cause symptoms requiring surgery. Including all women in mortality rate calculations underestimated the racial disparity in death rates between black and white women by 44 percent.

Current screening guidelines call for routine Pap smears to test for cervical cancer among women between 21 and 65. If women have had three healthy tests over the previous decade, they are no longer recommended for testing after the age of 65. An inexpensive Pap smear can find changes in the cervix before cancer develops. It can also find cervical cancer early, when it is in its most curable stage. Cervical cancer, which is caused by the human papillomavirus (HPV), can also be prevented by the HPV vaccine, which is offered to young people.

Rositch says it isn’t clear why older and black women are dying of cervical cancer at higher rates. Were they not properly screened? Was there no follow-up after an abnormal screening test? Was something missed during screening? Was treatment ineffective? Answering these questions are critical to identifying the most appropriate interventions that would lower these mortality rates.

Previous research suggests that black women are more likely to have their cervical cancer caught at a later stage of diagnosis and may receive different treatment than white women. One study found that black women had 50-percent lower odds of receiving surgery and 50-percent higher odds of receiving radiation compared to white women with the same stage and insurance.

While rare in the United States, cervical cancer is more common in the developing world. Worldwide, more than 500,000 women are diagnosed each year and more than 200,000 die. GLOBOCAN, an arm of the World Health Organization, estimated in 2012 that 9.8 women per 100,000 die of cervical cancer in less developed nations, including all of Africa, Asia (excluding Japan), Latin America and the Caribbean).

While trends over time show that the racial disparities gap has been closing somewhat, these data emphasize that it should remain a priority area,” Rositch says. “Black women are dying of cervical cancer at twice the rate as white women in the United States and we need to put in place measures to reverse the trend.”

Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States” was written by Anna Beavis, MD, MPH, Patti E. Gravitt, PhD, and Anne F. Rositch, PhD, MSPH. Collaborating institutions include the Johns Hopkins University School of Medicine and the George Washington University Milken Institute School of Public Health.

Beavis et al. Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States. Cancer. 2017;doi:10.1002/cncr.30507 [Abstract]

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Racial disparity lies at the intersection of HIV and Hodgkin lymphoma

A new study finds a significant racial disparity within a doubly troubled population of patients: those with HIV and Hodgkin lymphoma. In such cases, blacks are at significantly higher risk than whites of not receiving treatment for the cancer that in many cases would be effective.

Black patients have higher rates of not receiving treatment,” said lead author Dr. Adam Olszewski, associate professor of medicine in the Alpert Medical School of Brown University and a physician in the Cancer Center of Memorial Hospital in Pawtucket, R.I. “Hodgkin lymphoma is generally believed to be highly curable. We have an expectation to cure over 90 percent of early stage patients and even 70-80 percent of quite advanced cases.”

Olszewski’s study in the journal AIDS, conducted with Dr. Jorge Castillo of Dana-Farber Cancer Institute, identified the racial disparity in data from nearly 2,100 cases in the National Cancer Data Base between 2004 and 2012.

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​While the disparity is clear, Olsewski said, the root cause of it is not. Several closely entangled epidemiological, socioeconomic, and medical factors are at play.Heading into the study, researchers knew that people with HIV have a risk of Hodgkin lymphoma that is five to 20 times greater than people who do not have HIV. They also knew that HIV incidence has remained relatively high among blacks, while it has dropped significantly for whites. As a result, the new study found that between 2004 and 2012, blacks surpassed whites as the largest racial group with simultaneous HIV infection and Hodgkin lymphoma, making up 49 percent of such cases in 2012.

Meanwhile, doctors have had a muddy sense of whether HIV-positive people with Hodgkin lymphoma survive the cancer as well as people who are HIV-negative. Many HIV-positive patients didn’t tolerate an older treatment regime for the lymphoma, Olszewski said, but chemotherapy treatment has vastly improved in more recent years. While some small studies, particularly in Europe, have found that HIV status makes no difference to survival, observations in the U.S. population suggest that being HIV-positive makes survival less likely.

The new study, the largest to date, may reconcile that conflict. It shows that in the United States the reason people with HIV seem to fare worse with the cancer is because they are less likely to be treated for it.

Specifically, the study ostensibly showed that HIV-negative people had an 80 percent Hodgkin lymphoma survival rate five years after diagnosis, but HIV-positive people survived at a rate of only 66 percent over the same timeframe. But among HIV-positive patients, 16 percent went untreated. Among people in the study who did get lymphoma treatment, HIV-positive people were statistically just as likely to survive as HIV-negative people. The results apply to the majority of cases in which the subtype of Hodgkin lymphoma is determined.

Importantly, further statistical analysis showed that one of the main risk factors for an HIV-positive person going untreated was being black. Statistically adjusting for possibly confounding factors, HIV-positive blacks were 67 percent more likely than HIV-positive whites to go untreated for the lymphoma. Other risk factors, which are often related to race, were low income and lacking health insurance. Another was being over 60 years of age.

Olszewski acknowledged it’s not clear how the racial disparity arises. It could correlate with more advanced or poorly controlled HIV infection. It could also be a lingering assumption that HIV-positive patients (who are increasingly likely to be black) won’t tolerate the treatment well. Some patients may be declining treatment, either for HIV (thereby making them seem more vulnerable) or for the lymphoma itself. Another possibility is that the often-related socioeconomic status of being black and poor and uninsured makes it hard for patients to remain connected to care after diagnosis.

For patients who have HIV and Hodgkin lymphoma, treatment can be effective and tolerated, especially when the lymphoma subtype is known, Olszewski said, but doctors should understand that some patients many need extra assistance or attention to ensure they connect with that care.

To date, this study suggests, it’s apparent that some people who should get treatment aren’t getting it.

Olszewski et al., Outcomes of HIV-associated Hodgkin lymphoma in the era of antiretroviral therapy: analysis of the National Cancer Data Base. AIDS, 2016; doi: 10.1097/QAD.0000000000000986 [Abstract]

Genes of colon cancer recurrence differs among blacks, whites and Asians

The genetic makeup of colon cancer tumors and survival rates for patients with the disease differ by race, according to a study from researchers at the Mayo Clinic Cancer Center, published in the Journal of the National Cancer Institute.

These findings put the issue of race more prominently on the radar of investigators that cancer biology may contribute to race-based disparities,” says the study’s co-lead author, Harry Yoon, M.D., an oncologist at Mayo Clinic. “While it is too early to change the way we treat these patients, our results indicate that future studies are needed to examine potential biological drivers of these differences more closely.

According to the American Cancer Society, colon cancer is the third most common cancer in both men and women with more than 93,000 cases estimated to be diagnosed in 2015. Researchers have long known that blacks develop colon cancer at an earlier age and blacks with colon cancer are at higher risk of dying than whites. However, it has been difficult to identify why the differences in survival exist.

Researchers analyzed data from a large clinical trial of more than 3,000 patients with stage III colon cancer. The analysis revealed that tumors from whites, blacks, and Asians had different frequencies of mutations in two key cancer-related genes, BRAF and KRAS, which have been associated with worse outcomes. It also found that colon cancers were twice as likely to recur in black patients as in whites; however, the discrepancy was only evident in those under age 50.

Some of the potential reasons for this disparity include socio-economic factors, such as diagnosis at a later stage, decreased access to health care and suboptimal treatment.

The role of the biology of colon tumors according to race has not been examined as extensively,” says Dr. Yoon. “This biology can be reflected in the genetic makeup of tumors, as well as by whether and how quickly cancer returns after the patient has been treated.”

Dr. Yoon and his colleagues focused their efforts on finding out if colon cancers are genetically different based on race, as well as if race-based differences exist in recurrence rates. To do this, they examined data from a large clinical trial – Alliance N0147 – which included patients with stage III colon cancer from many centers in North America who all underwent surgery to remove their cancer and chemotherapy after surgery.

As part of the trial, the patients provided a self-description of their race as either white, Asian, or black or African-American. The researchers then evaluated the tumors from these participants to see if a mutation was present in the cancer-related genes BRAF and KRAS. They also noted if the cancer had returned after treatment.

Analysis of the data showed that tumors from whites, blacks and Asians were different in terms of the frequency of mutations in the BRAF and KRAS genes. Tumors from whites were twice as likely to have BRAF mutations; whereas, tumors from blacks had the highest frequency of KRAS mutations. Tumors from Asians were the most likely to have normal copies of both genes.

The analysis also indicated that the colon cancers among blacks had more than double the risk of cancer recurrence, compared to whites. However, this discrepancy was only visible among young patients – those under age 50. Almost half of younger black patients experienced colon cancer recurrence within five years, compared to only 22 to 35 percent of whites or Asian patients of any age.

This difference could not be explained by the genetic mutations most frequently found in the tumors of the different races. The researchers adjusted for a number of other potential confounders, such as tumor grade, the degree of lymph node involvement, depth of tumor invasion, body mass index, location of the tumor within the colon, history of smoking, and anomalies in mismatch repair genes; however, none seemed to affect the outcome for young blacks.

Because all patients were treated and had their disease monitored in a clinical trial,” says Dr. Yoon, “suboptimal treatment, differences in cancer stage, or reduced access to care cannot adequately explain the disparity.”

“In addition to published data indicating that a limited number of genes are preferentially mutated in colon cancers from black versus white patients, our study revealed differences in the mutation frequencies of BRAF and KRAS oncogenes that provide prognostic information in colon cancer patients,” says Frank Sinicrope, M.D., an oncologist at Mayo Clinic and co-lead author. “Our data provide further evidence that colon cancers from blacks are intrinsically different and are associated with more aggressive clinical behavior in young black patients.

​Yoon et al. Racial Differences in BRAF/KRAS Mutation Rates and Survival in Stage III Colon Cancer Patients. J Natl Cancer Inst. 2015; 107 (10): djv186 doi:10.1093/jnci/djv186 [Abstract]

Study sheds light on racial disparity in colon cancer

African-Americans half as likely to have genetic marker linked to better survival

African-Americans with colon cancer are half as likely as Caucasian patients to have a type of colon cancer that is linked to better outcomes. The finding may provide insight into why African-Americans are more likely to die of colon cancer than Caucasians with the same stage of disease.

The population-based study of 503 people with colon cancer found that 14 percent of Caucasians and 7 percent of African-Americans had a genetic marker called microsatellite instability, or MSI. These types of tumors are known to be resistant to the chemotherapy drug 5FU. Yet, even without chemotherapy, these patients tend to have better outcomes.

We know that patients with MSI colon cancer do better without chemotherapy. But these improved survival benefits are limited among African-Americans with colon cancer,” says lead study author John M. Carethers, M.D., John G. Searle Professor and Chair of internal medicine at the University of Michigan Medical School.

Results of the study appear in the journal PLOS ONE.

The researchers identified patients through the North Carolina Colon Cancer Study, a population-based, case-control study conducted throughout central and eastern North Carolina. The North Carolina study includes both rural and urban areas, creating adequate representation by African-American and rural residents.

The group of patients Carethers and his colleagues looked at was 45 percent African-American and 55 percent Caucasian. Researchers examined tissue samples taken at the time of surgery and assessed it for various markers, including MSI.

In addition to the racial imbalance in MSI, the researchers also found that African-Americans patients were more likely than Caucasian patients to have cancer on the right side of their colon. This is significant because right-sided colon cancer is easier to miss with screening and more likely to be found larger or more advanced than left-sided cancers.

Right-sided colon cancer may be the ‘black ice’ of the colon – unseen but potentially deadly. Strategies to better recognize and detect right-sided cancer may need to be pursued in a broader fashion,” Carethers says.

Carethers et al., (2014) Influence of Race on Microsatellite Instability and CD8+ T Cell Infiltration in Colon Cancer. PLoS ONE, 9(6): e100461. doi:10.1371/journal.pone.0100461 [Article]