Cervical cancer therapy access lacking
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HIV infection linked with death from cervical cancer

HIV-infected women with cervical cancer have significantly lower survival rates than women with cervical cancer who are not infected, investigators found.

A study of 348 women with invasive cervical cancer in Botswana, a nation with robust and wide-reaching HIV prevention and antiretroviral therapy (ART) programs, showed that women who had HIV infections had a twofold greater risk for death within 3 years than women without HIV, reported Scott Dryden-Peterson, MD, from the Brigham and Women’s Hospital and Harvard TH Chan School of Public Health in Boston, and his colleagues.

“Even in the context of good access to and use of ART, HIV infection more than doubled the risk of death among women who received curative guideline-concordant therapy. Competing mortality from HIV-associated infections seemed to contribute minimally to the excess risk of death; rather, earlier oncologic progression among women with HIV seemed to account for the excess mortality,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.9613).

It is well known that HIV infection significantly increases the risk of cervical cancer, with HIV-infected women having a sixfold greater risk for the malignancy than women in the general population, the investigators stated.

Whether HIV has a detrimental effect on cervical cancer–specific survival was unclear, however, prompting them to investigate the question in a cohort of 348 women, 231 of whom were infected with HIV, 96 of whom were free of infection, and 21 of whom had unknown HIV status.

Of the women with HIV, 189 (81.8%) had started on ART before their cancers were diagnosed, and had been on therapy for a median of 4.8 years. Most of the HIV-infected women had CD4 cell counts that fell in the moderate or mildly immunosuppressed range (median 397 cells per microliter). Of this group, only 24 had CD4 counts below 200, the threshold for a diagnosis of AIDS.

After a median follow-up of 19.7 months, 157 participants had died, including 117 women with HIV infections and 40 without infections.

Three-year survival, the primary outcome, was 35% for women with HIV, compared with 48% for uninfected women.

In an analysis adjusted for age, cancer stage, CD4 cell counts, duration of ART, radiation dose received and treatment intent (curative or palliative), the hazard ratio for death among women with HIV was 1.95 (P = .007).

In an analysis restricted to women who received therapy with curative intent, the HR was 2.35 (P = .002), and an analysis restricted to women who received therapy with curative intent that adhered to clinical guidelines showed that the HR for death among HIV-infected women was 2.65 (P = .037).

Of note, the detrimental effect of HIV on survival was highest among women with stage I (HR, 4.03) and stage II (HR, 2.44) cancers, compared with stages III or IV (P = .035).

Among women with CD4 cell counts below 250, the HR for death was 2.75. This risk diminished with increasing cell counts, but remained significantly higher among women with near-normal counts (350 to 500 cells/microliter; HR, 1.87; significant according to confidence intervals).

“Advanced stage and poor treatment completion contributed to high mortality overall,” the investigators wrote.

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Despite methodological concerns and the absence of detailed data about certain aspects, this study describes the importance of further research and investment into improving the outcomes of women with both HIV and cervical cancer. International collaboration through research networks, such as the recently established Cervix Cancer Research Network, that could provide infrastructure, quality assurance, financial support, data sharing, education, and expertise in conducting clinical trials can potentially help establish future initiatives to answer outstanding questions such as those highlighted by Dryden-Peterson et al. We commend these authors for their dedication to improve treatment for women with HIV and cervical cancer in this rising burden of disease that has had limited research to date.

One clear major barrier to optimal treatment of cervical cancer, and indeed many cancers, is access to radiation therapy. A recent analysis of radiation therapy infrastructure in 139 low- and middle-income countries found that only 4 (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. 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.

Linda R. Mileshkin, MD and Alison E. Freimund, MD are with the Peter MacCallum Cancer Centre, Melbourne. These comments are excerpted from an accompanying editorial (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.69.0784).

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Despite methodological concerns and the absence of detailed data about certain aspects, this study describes the importance of further research and investment into improving the outcomes of women with both HIV and cervical cancer. International collaboration through research networks, such as the recently established Cervix Cancer Research Network, that could provide infrastructure, quality assurance, financial support, data sharing, education, and expertise in conducting clinical trials can potentially help establish future initiatives to answer outstanding questions such as those highlighted by Dryden-Peterson et al. We commend these authors for their dedication to improve treatment for women with HIV and cervical cancer in this rising burden of disease that has had limited research to date.

One clear major barrier to optimal treatment of cervical cancer, and indeed many cancers, is access to radiation therapy. A recent analysis of radiation therapy infrastructure in 139 low- and middle-income countries found that only 4 (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. 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.

Linda R. Mileshkin, MD and Alison E. Freimund, MD are with the Peter MacCallum Cancer Centre, Melbourne. These comments are excerpted from an accompanying editorial (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.69.0784).

Body

Despite methodological concerns and the absence of detailed data about certain aspects, this study describes the importance of further research and investment into improving the outcomes of women with both HIV and cervical cancer. International collaboration through research networks, such as the recently established Cervix Cancer Research Network, that could provide infrastructure, quality assurance, financial support, data sharing, education, and expertise in conducting clinical trials can potentially help establish future initiatives to answer outstanding questions such as those highlighted by Dryden-Peterson et al. We commend these authors for their dedication to improve treatment for women with HIV and cervical cancer in this rising burden of disease that has had limited research to date.

One clear major barrier to optimal treatment of cervical cancer, and indeed many cancers, is access to radiation therapy. A recent analysis of radiation therapy infrastructure in 139 low- and middle-income countries found that only 4 (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. 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.

Linda R. Mileshkin, MD and Alison E. Freimund, MD are with the Peter MacCallum Cancer Centre, Melbourne. These comments are excerpted from an accompanying editorial (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.69.0784).

Title
Cervical cancer therapy access lacking
Cervical cancer therapy access lacking

HIV-infected women with cervical cancer have significantly lower survival rates than women with cervical cancer who are not infected, investigators found.

A study of 348 women with invasive cervical cancer in Botswana, a nation with robust and wide-reaching HIV prevention and antiretroviral therapy (ART) programs, showed that women who had HIV infections had a twofold greater risk for death within 3 years than women without HIV, reported Scott Dryden-Peterson, MD, from the Brigham and Women’s Hospital and Harvard TH Chan School of Public Health in Boston, and his colleagues.

“Even in the context of good access to and use of ART, HIV infection more than doubled the risk of death among women who received curative guideline-concordant therapy. Competing mortality from HIV-associated infections seemed to contribute minimally to the excess risk of death; rather, earlier oncologic progression among women with HIV seemed to account for the excess mortality,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.9613).

It is well known that HIV infection significantly increases the risk of cervical cancer, with HIV-infected women having a sixfold greater risk for the malignancy than women in the general population, the investigators stated.

Whether HIV has a detrimental effect on cervical cancer–specific survival was unclear, however, prompting them to investigate the question in a cohort of 348 women, 231 of whom were infected with HIV, 96 of whom were free of infection, and 21 of whom had unknown HIV status.

Of the women with HIV, 189 (81.8%) had started on ART before their cancers were diagnosed, and had been on therapy for a median of 4.8 years. Most of the HIV-infected women had CD4 cell counts that fell in the moderate or mildly immunosuppressed range (median 397 cells per microliter). Of this group, only 24 had CD4 counts below 200, the threshold for a diagnosis of AIDS.

After a median follow-up of 19.7 months, 157 participants had died, including 117 women with HIV infections and 40 without infections.

Three-year survival, the primary outcome, was 35% for women with HIV, compared with 48% for uninfected women.

In an analysis adjusted for age, cancer stage, CD4 cell counts, duration of ART, radiation dose received and treatment intent (curative or palliative), the hazard ratio for death among women with HIV was 1.95 (P = .007).

In an analysis restricted to women who received therapy with curative intent, the HR was 2.35 (P = .002), and an analysis restricted to women who received therapy with curative intent that adhered to clinical guidelines showed that the HR for death among HIV-infected women was 2.65 (P = .037).

Of note, the detrimental effect of HIV on survival was highest among women with stage I (HR, 4.03) and stage II (HR, 2.44) cancers, compared with stages III or IV (P = .035).

Among women with CD4 cell counts below 250, the HR for death was 2.75. This risk diminished with increasing cell counts, but remained significantly higher among women with near-normal counts (350 to 500 cells/microliter; HR, 1.87; significant according to confidence intervals).

“Advanced stage and poor treatment completion contributed to high mortality overall,” the investigators wrote.

HIV-infected women with cervical cancer have significantly lower survival rates than women with cervical cancer who are not infected, investigators found.

A study of 348 women with invasive cervical cancer in Botswana, a nation with robust and wide-reaching HIV prevention and antiretroviral therapy (ART) programs, showed that women who had HIV infections had a twofold greater risk for death within 3 years than women without HIV, reported Scott Dryden-Peterson, MD, from the Brigham and Women’s Hospital and Harvard TH Chan School of Public Health in Boston, and his colleagues.

“Even in the context of good access to and use of ART, HIV infection more than doubled the risk of death among women who received curative guideline-concordant therapy. Competing mortality from HIV-associated infections seemed to contribute minimally to the excess risk of death; rather, earlier oncologic progression among women with HIV seemed to account for the excess mortality,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.9613).

It is well known that HIV infection significantly increases the risk of cervical cancer, with HIV-infected women having a sixfold greater risk for the malignancy than women in the general population, the investigators stated.

Whether HIV has a detrimental effect on cervical cancer–specific survival was unclear, however, prompting them to investigate the question in a cohort of 348 women, 231 of whom were infected with HIV, 96 of whom were free of infection, and 21 of whom had unknown HIV status.

Of the women with HIV, 189 (81.8%) had started on ART before their cancers were diagnosed, and had been on therapy for a median of 4.8 years. Most of the HIV-infected women had CD4 cell counts that fell in the moderate or mildly immunosuppressed range (median 397 cells per microliter). Of this group, only 24 had CD4 counts below 200, the threshold for a diagnosis of AIDS.

After a median follow-up of 19.7 months, 157 participants had died, including 117 women with HIV infections and 40 without infections.

Three-year survival, the primary outcome, was 35% for women with HIV, compared with 48% for uninfected women.

In an analysis adjusted for age, cancer stage, CD4 cell counts, duration of ART, radiation dose received and treatment intent (curative or palliative), the hazard ratio for death among women with HIV was 1.95 (P = .007).

In an analysis restricted to women who received therapy with curative intent, the HR was 2.35 (P = .002), and an analysis restricted to women who received therapy with curative intent that adhered to clinical guidelines showed that the HR for death among HIV-infected women was 2.65 (P = .037).

Of note, the detrimental effect of HIV on survival was highest among women with stage I (HR, 4.03) and stage II (HR, 2.44) cancers, compared with stages III or IV (P = .035).

Among women with CD4 cell counts below 250, the HR for death was 2.75. This risk diminished with increasing cell counts, but remained significantly higher among women with near-normal counts (350 to 500 cells/microliter; HR, 1.87; significant according to confidence intervals).

“Advanced stage and poor treatment completion contributed to high mortality overall,” the investigators wrote.

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Key clinical point: HIV infection appears to be an independent risk factor for worse survival among women with invasive cervical cancer.

Major finding: Three-year survival was 35% for women with HIV, compared with 48% for uninfected women.

Data source: Prospective study of 348 women with invasive cervical cancer treated in Botswana.

Disclosures: The study was supported by grants from the US National Institutes of Health and the Paul G. Allen Family Foundation. Dr. Dryden-Peterson disclosed royalties for articles, two co-authors, and editorialists Dr. Mileshkin and Dr. Freimund disclosed relationships with various pharmaceutical companies.