Improvement of Outcomes for Women With HIV Infection and Cervical Cancer

Patients with HIV infection are at an increased risk for certain cancers. With 36.7 million individuals estimated to be living with HIV worldwide, only 46% receive antiretroviral treatment. Human papillomavirus (HPV) –associated malignancies occur in excess among patients with HIV, with cervical cancer designated as an AIDS-defining condition. Of note, although the introduction of highly active antiretroviral treatment (HAART) has reduced the incidence of some cancer types in those living with HIV, such as Kaposi’s sarcoma and CNS non-Hodgkin lymphoma, the incidence of cervical cancer has not decreased. The link among HPV, HIV, and cervical cancer is becoming better understood and attributed to enhanced HPV carcinogenesis in the setting of HIVrelated immunosuppression as well as more frequent infections, withmultiple and/or high-risk HPV subtypes inwomenwith HIV. In a study of . 309,000 US patients with HIV from 5 years before the date of HIV onset to 5 years after, the incidence of cervical cancer was documented to be significantly increased in women with HIV infection (relative risk, 5.4; 95% CI, 3.9 to 7.2). Some evidence also suggests that cervical cancer is more aggressive in women with HIV, who are more likely to present with more advanced-stage disease and respond less well to therapy. Cervical cancer remains the fourth leading cause of cancer death in women worldwide and is the leading cause of cancer death in women with HIV in sub-Saharan Africa. Because the majority of the disease burden is seen in lowand middle-income countries, with regions of a high prevalence of cervical cancer corresponding with regions of a high prevalence ofHIV infection, our understanding of the impact of concurrent HIV on cervical cancer and its response to treatment is paramount. The implementation of routine Papanicolaou smears in developed countries has led to the detection of early cervical cancers curable with surgery alone. Similarly, the development of the cervical cancer vaccine is expected to significantly reduce the incidence of cervical cancer over the next 60 years. Despite this, women in the developing world and even disadvantaged areas of developed countries continue to have low vaccination and Papanicolaou test rates, which result in more locally advanced stages of cervical cancer at diagnosis. For example, in Botswana, a country in sub-Saharan Africa, cervical cancer is the leading cause of cancer death in women, with more than two thirds of cases occurring in women with HIV infection. The national prevalence of HIV in Botswana is 17% to 24%. In South Africa, cervical cancer is the most common cancer; however, despite this, the country’s cancer screening policy is only able to offer asymptomatic women three free cervical smears in a lifetime, which begin at age 30 years and are performed 10 years apart. For women with HIV and CD4 T-cell counts , 350 cells/mL, screening is done annually. The problem is compounded by the lack of knowledge about the survival interplay between HIV and cervical cancer. However, should these dual diagnoses predict worse outcomes, then a modified treatment approach may be required. Most concerning is that the last major improvement in cervical cancer survival was based on reports published 17 years ago and later confirmed in a large meta-analysis in 2008, which demonstrated the superiority of cisplatin-based chemoradiation to radiation therapy alone and resulted in a low 58% versus 50% 5-year disease-free survival. No subgroup analysis of the potential confounding effects of a concurrent HIV infection on outcome was possible because patients with HIVare commonly excluded from clinical trials in oncology. In the article that accompanies this editorial, Dryden-Peterson et al present results of a prospective cohort of 348 women with cervical cancer treated in Botswana from 2010 to 2015. The primary objective was to determine the impact of concurrent HIV infection, which was present in two thirds of the cohort, on survival. Their conclusion is that despite good access to and use of antiretroviral treatment in 82% of the women before a cancer diagnosis, HIV infection significantly decreases survival from cervical cancer. Specifically, 3-year survival for the group with HIV infection was only 35% (95% CI, 27% to 44%) compared with 48% in the group without HIV infection (95% CI, 35% to 60%), with the majority of the deaths attributable to the cancer rather than to HIV. This occurred despite the fact that patients with HIV were younger, (median age, 42 years) compared with patients without HIV (median age, 58 years), had significantly greater access to education, and higher measures of wealth than those without HIV. Another concerning finding is that although the majority (82.9%) of patients were considered candidates for potentially curative therapy, the radiotherapy completion rates were far from ideal. Specifically, 30.6% of the cohort were considered to have received an inadequate radiotherapy dose, with only 61.2% completing the planned brachytherapy, some of which had to be administered in another country. Furthermore, only 80.8% received at least one dose