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HIV infection increases mortality in African women with cervical cancer
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Women with cervical cancer and HIV experienced significantly worse survival outcomes, despite access to antiretroviral treatment, according to a study conducted in Botswana.
Cervical cancer is the most frequent cause of death among African women. Women with HIV have a sixfold increased cervical cancer incidence.
Little study has addressed the impact of HIV infection on survival among women with cervical cancer, although some observations suggested that survival may be poorer in these women.
“Botswana was the first country in Africa to provide comprehensive HIV treatment to its citizens and has one of the most effective antiretroviral treatment programs globally,” Scott Dryden-Peterson, MD, instructor of medicine at Harvard Medical School and associate physician at Brigham and Women’s Hospital, told HemOnc Today. “As such, trends in Botswana are indicative of what will happen in other heavily HIV affected countries that also now have good access to HIV treatment. Botswana also has provided its citizens with access to guideline-concordant therapy for cervical cancer. These factors make Botswana and ideal location to understand the emerging co-epidemic of HIV and cervical cancer in order to direct our response.”
The study included data from 327 women (median age, 45.1 years; interquartile range [IQR], 38.8-54.4) with known HIV status (HIV infection, n = 231; no HIV infection, n = 96) between 2010 and 2015.
Women with HIV were significantly younger than women without HIV (median age, 41.5 years vs. 57 years; P < .001).
The majority of women with HIV (81.8%; n = 189) received antiretroviral therapy prior to their cancer diagnosis (median duration of antiretroviral therapy, 4.8 years; IQR, 1.6-8.6).
Women with HIV had a median CD4 cell count of 397 cells/L (IQR, 264-554); 10.4% (n = 24) of women had a CD4 count below 200 cells/L.
Women enrolled in the study received standard therapy for cervical cancer, including external-beam radiation therapy (45-50 Gy) with concurrent cisplatin (35 mg/m2), followed by brachytherapy.
Median follow-up was 19.7 months.
A total of 157 patients died (HIV infection, n = 117; no HIV infection, n = 40). The researchers attributed one death to HIV. The majority of deaths (HIV infection, n = 102; no HIV infection, n = 38) were attributed to cancer.
The 3-year survival rate was 35% (95% CI, 27-44) among women with HIV and 48% (95% CI, 35-60) among women without HIV.
An adjusted analysis showed that women with HIV had a significantly higher risk for death than women without HIV (HR = 1.95; 95% CI, 1.2-3.17).
An analysis that only included women treated with a curative intent showed similar outcomes (HR = 2.35; 95% CI, 1.36-4.06). Women who received guideline-concordant curative treatment also demonstrated a higher mortality risk (HR = 2.63; 95% CI, 1.05-6.55).
The greatest adverse effect of HIV infection occurred in women with more localized disease (P = .035), women treated with curative intent (P = .003) and women with lower CD4 cell counts (P = .036).
Forty-eight percent of patients with HIV (n = 85) and 48% of women without HIV (n = 40) completed recommended radiation therapy. Researchers noted a sizable amount of women in both arms (HIV infection, n = 50; no HIV infection, n = 29) received an inadequate radiation dose.
The researchers determined that poor completion rates, as well as advanced-stage disease, contributed to the study’s high mortality rate.
“Further work is needed to better understand barriers to treatment completion,” Dryden-Peterson and colleagues wrote. “Due to limited documentation, we were unable to determine with confidence that access to and tolerability of cisplatin was not affected by HIV status or to determine the proportion of participants who received guideline-concordant therapy.”
Other study limitations included the lack of cross-sectional imaging during staging evaluation, as well as limited available data on relapses and death.
“Antiretroviral therapy, either of the infected or uninfected partner, is the most effective HIV prevention modality,” Dryden-Peterson said. “This is being expanded further in Botswana, but with nearly a quarter of adults infected and most early infections asymptomatic, incidence of new infection remains high (although well down from peak). HPV vaccine is being given to girls and cervical dysplasia screening via pap smear, VIA see-and-treat, and HPV screening pilots. However, these modalities face logistic challenges in resource constrained environments like Botswana. Also, these approaches will not have a population impact for many years. Further investigation is needed to understand how to overcome with poorer outcomes of HIV–associated cervical cancer, possibly with immune adjuvants or immune checkpoint inhibition.”
Improving access to radiation therapy could potentially improve treatment completion rates and outcomes in women with cervical cancer who reside in low-income countries, Linda R. Mileshkin, MBBS, and Alison E. Freimund, MD, medical oncologists at Peter MacCallum Cancer Centre in Melbourne, Australia, wrote in an accompanying editorial.
“A recent analysis of radiation therapy infrastructure in 139 low- and middle-income countries found that only four (2.87%) have the requisite number of teletherapy units to manage the estimated burden of cancer in 2020 and that 55 (39.5%) have no radiation facilities,” Mileshkin and Freimund wrote. “Another analysis of radiotherapy resources found that brachytherapy is available in only 20 of 52 African countries. If we are to reduce the number of deaths from cervical cancer in women with and without HIV, it is paramount that access to screening, vaccination, and treatment facilities in those areas of the world with the greatest burden of disease is addressed.” – by Cameron Kelsall
For more information:
Scott Dryden-Peterson, MD, can be reached at sldrydenpeterson@bwh.hardvard.edu.
Disclosure: Dryden-Peterson reports royalties from UpToDate. Please see the full study for a list of all other researchers’ relevant financial disclosures. Mileshkin reports research funding from Hospira and travel expenses from Merck Sharp & Dohme and Roche. Freimund reports travel expenses from Bristol-Myers Squibb and Roche.
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