Cytology compared with Hybrid Capture 2 human papilloma virus cervical cancer screening in HIV positive and HIV negative South African women.

OBJECTIVES: Cervical cancer is preventable and caused by persistent infection with oncogenic human papilloma virus (HPV) types. HPV screening is more sensitive and is the preferred screening test. HPV screening data are mainly from developed settings, and the purpose of this study was to investigate the performance of HPV screening in previously unscreened HIV positive and negative women. METHODS: In this cross sectional multicenter study, liquid based cytology and HPV testing were performed on women attending different clinics. Patients with positive screening tests had colposcopy and biopsy or large loop excision of the transformation zone. Some women with normal screening had colposcopy and biopsy. Data of women with histology results, and data of HIV positive and negative women were analyzed for comparison. For women without histology results, data were imputed using a statistical model. RESULTS: In 903 women with known HIV status, 683 (75.6%) had negative cytology, 202 women (22.4%) had abnormal cytology, and in 18 patients (2.0%) the results were uncertain. Mean age was 41.4 years (range 25-65). HPV tests were negative in 621 women (68.8%). In HIV positive women, 54.5% tested negative compared with 79.7% HIV negative women (p<0.0001). HPV screening had higher sensitivity (60.9%), but lower specificity (82.4%), compared with cytology (48.6% and 86.7%) for detection of cervical intraepithelial neoplasia (CIN) 2+ in all women. For detection of CIN 3+, HPV screening had higher sensitivity (70.4%) compared with cytology (62.9%), and specificity (75.5%) was lower compared with cytology at a threshold of atypical squamous cells of undetermined significance (ASCUS+) (82.4%). CONCLUSION: HPV screening was more sensitive than cytology in HIV positive and HIV negative women, but specificity was lower. Although HPV screening should be the preferred screening test, cytology is a suitable screening test in HIV positive women in low resource settings. TRIAL REGISTRATION NUMBER: NCT02956031.

DNA damage response of haematopoietic stem and progenitor cells to high-LET neutron irradiation.

The radiosensitivity of haematopoietic stem and progenitor cells (HSPCs) to neutron radiation remains largely underexplored, notwithstanding their potential role as target cells for radiation-induced leukemogenesis. New insights are required for radiation protection purposes, particularly for aviation, space missions, nuclear accidents and even particle therapy. In this study, HSPCs (CD34+CD38+ cells) were isolated from umbilical cord blood and irradiated with 60Co γ-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 h post-irradiation, a significantly higher number of 1.28 ± 0.12 γ-H2AX foci/cell was observed after 0.5 Gy neutrons compared to 0.84 ± 0.14 foci/cell for photons, but this decreased to similar levels for both radiation qualities after 18 h. However, a significant difference in late apoptosis was observed with Annexin-V+/PI+ assay between photon and neutron irradiation at 18 h, 43.17 ± 6.10% versus 55.55 ± 4.87%, respectively. A significant increase in MN frequency was observed after both 0.5 and 1 Gy neutron irradiation compared to photons illustrating higher levels of neutron-induced cytogenetic damage, while there was no difference in the nuclear division index between both radiation qualities. The results point towards a higher induction of DNA damage after neutron irradiation in HSPCs followed by error-prone DNA repair, which contributes to genomic instability and a higher risk of leukemogenesis.

HIV status does not have an impact on positron emission tomography-computed tomography (PET-CT) findings or radiotherapy treatment recommendations in patients with locally advanced cervical cancer.

INTRODUCTION: Positron emission tomography-computed tomography (PET-CT) imaging is commonly used to identify nodal involvement in locally advanced cervical carcinoma, but its appropriateness for that purpose among HIV-positive patients has rarely been studied. We analyzed PET-CT findings and subsequent treatment prescribed in patients with locally advanced cervical carcinoma in Cape Town, South Africa. METHODS: We identified a cohort of consecutive cervical carcinoma patients International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIB at our cancer center who underwent a planning 18-fluorodeoxyglucose (18FDG) PET-CT scan from January 2015 through December 2018. Demographics, PET-CT findings, and subsequent treatment prescribed were recorded. Patients were selected for PET-CT only if they had no signs of distant disease on staging chest X-ray or abdominal ultrasound; were deemed suitable for radical chemoradiation by the multi-disciplinary team; and had normal renal function. HIV-positive patients ideally had to have been established on continuous antiviral therapy for more than 3 months and to have a CD4 cell count above 150 cells/µL. Small cell and neuroendocrine carcinoma cases were excluded from the study. Differences in demographic and clinical measures between HIV-positive and HIV-negative patients were evaluated by means of t-tests for continuous variables and χ2 tests for categorical variables. RESULTS: Over a 4 year period, 278 patients-192 HIV-negative (69.1%) and 86 HIV-positive (30.9%)-met the inclusion criteria. HIV-positive patients had a median CD4 count of 475 cells/µL (IQR 307-612 cells/µL). More than 80% of patients had pelvic nodal involvement, and more than 40% had uptake in common iliac and/or para-aortic nodes. Nodal involvement was not associated with HIV status. Fifty-four patients (19.4%) had at least one site of distant metastatic disease. Overall, 235 patients (84.5%) were upstaged following PET-CT staging scan. Upstaging was not associated with HIV status (HIV-negative 83.9% vs HIV-positive 87.2%; p=0.47). Ten patients who did not return for radiotherapy were excluded from the analysis. Following their PET-CT scan, treatment intent changed for 124 patients (46.3%): 53.6% of HIV-positive patients and 42.9% of HIV-negative patients (p=0.11). CONCLUSION: We found no differences between HIV-positive or HIV-negative patients in nodal involvement or occult metastases, and PET-CT imaging did not lead to, or justify, treatment differences between the two groups. Future studies will evaluate survival and correlation of upstaging with outcome.

Progression and persistence of low-grade cervical squamous intraepithelial lesions in women living with human immunodeficiency virus.

OBJECTIVE: This study aimed to investigate the progression and persistence of low-grade squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)-infected women. METHODS: Study participants for this retrospective cohort study were 1,720 women who had LSIL as their first abnormal Pap smear. A comparison of the survival of LSIL without progression to high-grade SIL as progression-free time and the survival of SIL without clearance of the lesion as persistence of SIL was done for women of HIV-positive, HIV-negative, or unknown status using the Kaplan-Meier method. Multivariable Cox proportional hazards regression model was applied to identify independent risk factors for disease progression or persistence. RESULTS: We found progression of LSIL not different between HIV groups but that persistence occurred more in HIV-positive women (63.8% vs 35.0%, p < .001). For the HIV group, antiretroviral therapy that was started before the first LSIL was associated with decreased risk for progression compared with no antiretroviral therapy (hazard ratio = 0.66, 95% CI = 0.54-0.81, p < .001). Antiretroviral therapy also improved clearance when corrected for excision treatment and age (hazard ratio = 1.71, 95% CI = 1.29-2.27, p < .001). Excision of LSIL reduced the risk of progression. In HIV-negative women, progression was reduced from 54.7% to 0.0% (p < .001), and from 46.9% to 6.4% in HIV-positive women (p < .001). Excision also reduced persistence in HIV-negative women from 39.5% to 7.1% (p = .001), but for HIV-positive women, the effect was smaller (from 66.3% to 45.5%, p < .001). CONCLUSIONS: Antiretroviral treatment reduced the risk for progression and persistence of LSIL in HIV-infected women.