Characterization of HPV subtypes in invasive cervical cancer in Botswana patients using a pan-pathogen microarray technology

Abstract

Human papillomavirus (HPV) plays a significant role in the development of cervical cancers in the setting of co-infection with HIV. Botswana has a high prevalence of HIV and cervical cancer. In this study, we investigated the distribution of HPV subtypes in cervical cancer biopsy samples from patients in Botswana using a highly sensitive pan-pathogen microarray technology, PathoChip, to detect both high- (HR-HPV) and low-risk HPV (LR-HPV) subtypes in women living with HIV (WLWH) and women living without HIV. We analyzed samples from 168 patients, of which 73% (n = 123) were WLWH with a median CD4 count of 479.5 cells/μL. Five HR-HPV subtypes were detected in the cohort: HPV 16, 18, 26, 34, and 53. The most prevalent subtypes were HPV 26 (96%) and HPV 34 (92%); 86% of WLWH (n = 106) had co-infection with four or more HR-HPV subtypes compared to 67% (n = 30) of women without HIV (p < 0.01). We detected 66 LR-HPV subtypes among all cervical cancer patients, with HPV 6b and 48 being most prevalent. Notably, signatures for LR-HPV subtypes 10, 41, 90, and 129 were only detected in WLWH. Signal intensity for HPV 18 was significantly weaker in WLWH with CD4 levels ≤200 cells/μL as compared to patients with >200 cells/μL and HIV-negative patients. Although the majority of cervical cancer specimens in this cohort were determined to have multiple HPV infections, the most prevalent HR-HPV subtypes (HPV 26 and HPV34) found in these cervical cancer samples are not covered in the current HPV vaccines. Though no conclusions can be made on the direct carcinogenicity of these subtypes the results do underlie the need for continued screening for prevention of cervical cancer.

Keywords: Africa; Cervical cancer; HIV; HPV subtypes; High risk HPV.

Fig. 1A

High-risk HPV subtype prevalence and hybridization signal intensity (HSI) by HIV status and age group.

Fig. 1B

Low-risk HPV prevalence and hybridization signal intensity (HSI) by HIV status and age group.

Fig. 2A

High-risk HPV subtype hybridization signal intensity (HSI) by CD4 cell count and HIV status. *Comparison of HPV subtype across CD4 ranges; #Comparison of HPV subtypes within the same CD4 category.

Fig. 2B

Low-risk HPV hybridization signal intensity (HSI) by CD4 cell count and HIV status. *Comparison of HPV subtype across CD4 ranges; #Compare of HPV subtypes with the same CD4 category.

Fig. 3A

High-risk HPV subtype prevalence and hybridization signal intensity (HSI) by HIV status and stage group.

Fig. 3B

Low-risk HPV subtype prevalence and hybridization signal intensity (HSI) by HIV status and stage group.