PurposeTo provide evidence-based, resource-stratified global recommendations to clinicians and policymakers on the management and palliative care of women diagnosed with invasive cervical cancer.MethodsASCO convened a multidisciplinary, multinational panel of cancer control, medical and radiation oncology, health economic, obstetric and gynecologic, and palliative care experts to produce recommendations reflecting resource-tiered settings. A systematic review of literature from 1966 to 2015 failed to yield sufficiently strong quality evidence to support basic- and limited-resource setting recommendations; a formal consensus-based process was used to develop recommendations. A modified ADAPTE process was also used to adapt recommendations from existing guidelines.ResultsFive existing sets of guidelines were identified and reviewed, and adapted recommendations form the evidence base. Eight systematic reviews, along with cost-effectiveness analyses, provided indirect evidence to inform the consensus process, which resulted in agreement of 75% or greater.RecommendationsClinicians and planners should strive to provide access to the most effective evidence-based antitumor and palliative care interventions. If a woman cannot access these within her own or neighboring country or region, she may need to be treated with lower-tier modalities, depending on capacity and resources for surgery, chemotherapy, radiation therapy, and supportive and palliative care. For women with early-stage cervical cancer in basic settings, cone biopsy or extrafascial hysterectomy may be performed. Fertility-sparing procedures or modified radical or radical hysterectomy may be additional options in nonbasic settings. Combinations of surgery, chemotherapy, and radiation therapy (including brachytherapy) should be used for women with stage IB to IVA disease, depending on available resources. Pain control is a vital component of palliative care. Additional information is available at www.asco.org/rs-cervical-cancer-treatment-guideline and www.asco.org/guidelineswiki. It is the view of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Cervical cancer is the leading cause of cancer death among women in Uganda. Given the high prevalence of genital human papillomavirus infection, the current unavailability of radiotherapy, and the absence of a national cervical cancer prevention and control program, these deaths will likely increase. Efforts to organize an effective cervical cancer screening and treatment program will require adequate financial resources, the development of infrastructure, training needed manpower, and surveillance mechanisms of the targeted women. Screening with VIA (visual inspection with acetic acid) and HPV DNA testing on self-collected samples with processing at a specific site could, for the first time, make national, large-scale population-based screening feasible in Uganda. Combining screening efforts with timely treatment of all screen positives for HPV infection can prevent progression to invasive cervical cancer. To date, this is the most effective intervention in closing the current prevention gap.Training of health professionals, ongoing construction of new radiotherapy bunkers, and opening of regional centers are all geared towards improving cervical cancer care in Uganda. The Uganda Cancer Institute Bill establishes the Institute as a semi-autonomous agency mandated to undertake and coordinate the prevention and treatment of cancer. Its implementation will be a milestone in cervical cancer prevention and control. However, execution will require political will and an increase in domestic and international investment.

ersistent HPV infection, in episomal or integrated form, is necessary but not sufficient for the development of cervical cancer 1. HPV-16 and HPV-18 are detected in at least 70% of affected individuals 2. HPV-16 (clade A9) is common in both squamous cell carcinomas and adenocarcinomas, while HPV-18 (clade A7) is associated with adenocarcinomas 2 and inferior survival 3-5. Cervical cancer prevention strategies include vaccination and screening for HPV and treatment of high-grade precancer. Although effective 6 , vaccine use remains low in low-and middle-income countries 7 where HIV is prevalent. Resource constraints similarly complicate screening, surgery 8 and radiotherapy 9 , such that a 50% increase in cervical cancer mortality by 2040 is predicted 10. Genomic cervical cancer studies, primarily conducted in non-African individuals 11,12 , identified APOBEC mutational signatures, copy number amplifications of CD274 (PD-L1) and PDCD1LG2 (PD-L2), somatic alterations affecting the PI(3)K-MAPK and TGFβR2 pathways 11,12 and mutations in chromatin modifier genes 11-13. Studies in HPV-infected individuals with head and neck squamous cell carcinomas linked HPV integration to changes in histone modification 14 and DNA methylation 15 , suggesting the potential for similar findings in cervical cancer. As part of the National Cancer Institute's (NCI's) HIV+ Tumor Molecular Characterization Project (HTMCP), we characterized the genomic, transcriptomic and epigenomic landscapes of cervical cancers from Ugandan patients. We identified previously uncharacterized differences in the epigenomes and transcriptomes of cervical tumors from individuals infected by different HPV clades and note that these clades appear relevant to prognosis. Results Patient samples and clinical data. Our cohort of 212 patients with cervical cancer received treatment at the Uganda Cancer Institute in Kampala. Of these, 118 made up our discovery cohort and 89 made up our extension cohort (Supplementary Tables 1 and 2, and Methods). HIV + patients (72/118, 61%) were 10 years younger, on average, than HIV-negative (HIV-) patients (mean, 42.9 versus 52.4 years).