The impact of HIV status on staging, treatment and outcomes in locally advanced cervical carcinoma

Simonds, Hannah (2019-12)

Thesis (PhD)--Stellenbosch University, 2019.

Thesis

ENGLISH ABSTRACT: Cervical carcinoma is one of the most frequently diagnosed malignancies in women in many countries in sub-Saharan Africa, including South Africa. In sub-Saharan Africa, among women without HIV the age-standardised cervical cancer incidence rate is greater than 40 per 100 000. However, women infected with both the human-immunodeficiency virus (HIV) and the human papilloma virus (HPV) have a higher risk of developing cervical carcinoma than women infected with HPV alone. Published studies of the ideal staging methods, treatment algorithms, and outcomes for women with comorbid locally advanced cervical carcinoma and HIV are scarce. The aim of this body of work is to fill some of these gaps. We conducted four cohort studies of patients with locally advanced cervical carcinoma with or without HIV, recording demographic data, staging information and treatment delivered. Additional information gathered for individual studies included treatment response and survival outcomes. We evaluated the statistical significance of differences between HIV-positive and negative patients. Logistic regression models were utilised to evaluate risk for toxicity, treatment response, and survival outcomes. In the first of three retrospective cohort studies, among 383 patients, early response to chemoradiation was found to be related to advanced stage [OR 2.39, 95% CI 1.45-3.96] and completion of brachytherapy [OR 3.14; 95% CI 1.24-7.94] but not HIV status. In the second retrospective study, among 213 patients undergoing radical radiotherapy, acute Grade 3 / 4 toxicity was associated with receiving chemotherapy [OR4.41; 95%CI 1.76- 11.1; p 0.023] and having HIV [OR 2.16; 95% CI0.98-4.8; p 0.05]. In a prospective study of 492 patients, OS at 5 years was 49.5% (95%CI; 44.6% - 54.4%) among HIV-negative patients but only 35.9% (95% CI; 23.9% - 48.0%) among HIV-positive patients (p=0.002). In our Cox models, factors affecting outcome were HIV infection, stage IIIB disease, hydronephrosis, and delivery of concurrent chemotherapy. In the fourth cohort study, among 273 patients with locally advanced cervical carcinoma who underwent a radiotherapy planning PET-CT scan, overall 235 (84.5%) were upstaged. Upstaging was not associated with HIV status (HIV-negative 83.9% vs HIV-positive 87.2%; p=0.47). Following the PET-CT scan, among the 263 patients who attended for radiotherapy treatment, intent changed for 124 patients (46.3%): 53.6% of HIV-positive patients and 42.9% of HIV-negative patients (p=0.11). This body of work demonstrated that in HIV-positive patients, integration of PET-CT into staging algorithms for cervical carcinoma is a viable option. During treatment HIV-positive patients experienced increased toxicity, but most were able to complete treatment, and their 5-year overall survival was nearly 40%. Among women with locally advanced cervical cancer, those with HIV infection should be treated with the best standard of care. Future research should focus on factors that improve outcomes for these women.

AFRIKAANSE OPSOMMING: Servikale karsinoom is een van die mees gediagnoseerde kwaadaardige gewasse in vroue in baie lande in sub-Sahara Afrika, insluitende Suid-Afrika. Die voorkoms van servikale kanker is meer as 40 per 100 000 (ouderdom-gestandaardiseerde koers) in sub- Sahara Afrika, selfs onder vroue sonder menslike immuniteitsgebrek virus (MIV). Vroue met beide MIV en menslike papilloom virus (MPV) infeksies het 'n hoër risiko vir die ontwikkeling van servikale karsinoom as vroue wat slegs MPV infeksie het. Daar is 'n tekort aan gepubliseerde werk oor die ideale stadiërings ondersoeke, behandeling algoritmes en uitkomste vir vroue met lokaal gevorderde servikale karsinoom en MIV infeksie. Verder dit is onduidelik wat die impak van MIV-positiwiteit mag hê op hierdie parameters. Die doel van hierdie navorsing is om sommige van hierdie vrae te antwoord. Pasiënte, met of sonder MIV en lokaal gevorderde servikale karsinoom is in vier kohort studies bestudeer. In al die studies is inligting versamel oor demografie, stadiëring en die behandeling ontvang. Bykomende inligting vir individuele studies het respons op behandeling en oorlewing-uitkomste ingesluit. Die statistiese betekenisvolheid van verskille tussen MIV-positiewe en negatiewe pasiënte is bereken. Logistiese regressie modelle is gebruik om die risiko vir newe-effekte, behandelingsuitkoms en oorlewing te evalueer. In die eerste van die drie terugskouende kohort studies op 383 pasiënte, is bevind dat vroeë reaksie op chemo- bestraling betekenisvol verband hou met gevorderde stadium van karsinoom [KV 2.39, 95% VI 1.45- 3.96] en voltooiing van bragiterapie [KV 3.14; 95% VI 1.24-7.94] maar nie met MIV status nie. In die tweede terugskouende studie, wat 213 pasiënte ingesluit het wat radikale radioterapie ondergaan het, was akute graad 3 / 4 toksisiteit betekenisvol geassosieer met byvoeging van chemoterapie [KV4.41; 95% VI 1.76-11.1; p 0.023] en MIV positiwiteit [KV 2.16; 95% VI 0.98-4.8; p 0.05]. Vyf jaar algehele oorlewing is in 'n prospektiewe studie van 492 pasiënte geëvalueer. Die algehele oorlewing van MIV-negatiewe pasiënte was 49.5% (95% VI 44.6% – 54.4%) teen 5 jaar. Die algehele oorlewing van MIV-positiewe pasiënte was aansienlik laer, 35.9% (95% VI 23.9% – 48.0%) teen 5 jaar (p = 0.002). In die Cox modelle was die faktore wat uitkoms beïnvloed het, MIV-infeksie, stadium IIIB siekte, die teenwoordigheid van hidronefrose en toediening van gelyktydige chemoterapie. In die vierde kohort studie van 273 pasiënte met lokaal gevorderde servikale karsinoom, het pasiënte vir radioterapie beplanning 'n Pet-RT (rekenaar tomografie) skandering ontvang. In totaal is 235 pasiënte (84.5%) se stadiëring verhoog weens die bykomende inligting verkry van Pet-RT skandering. Verhoging in stadium het nie verband gehou met MIV-status nie (MIV-negatiewe 83.9% teenoor MIV-positiewe 87.2%; p = 0.47). Van die 263 pasiënte wat wel radioterapie behandeling ontvang het, is die plan verander vir 124 pasiënte as gevolg van die Pet-RT skandering (46.3%), 53.6% van MIV-positiewe pasiënte en 42.9% van MIV-negatiewe pasiënte (p = 0.11). Hierdie navorsing het getoon dat integrasie van Pet-RT in stadiëring algoritmes vir servikale karsinoom 'n redelike opsie is vir MIV-positiewe pasiënte. Verder is aangetoon MIV-positiewe pasiënte meer newe-effekte ervaar tydens behandeling, maar in staat is om behandeling in die meerderheid van gevalle te voltooi met 'n 5-jaar algehele oorlewing van bykans 40%. In vroue met lokaal gevorderde servikale kanker moet diegene met MIV-infeksie met die beste standaard van sorg behandel word. Toekomstige navorsing moet fokus op faktore wat uitkomste verbeter vir hierdie vroue.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/107293
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