Background: Invasive cervical carcinoma (ICC) accounts for 23% of all cancer-related deaths in Zimbabwean women. Trials for a national program of genotype-specific human papillomavirus (HPV) vaccines are underway to prevent cervical carcinoma, but the distribution of HPV types among women with ICC according to HIV status is unknown. Methods: To determine prevalence and distribution of high-risk HPV genotypes by HIV status in women with ICC, we performed a cross-sectional study on women referred for ICC testing at 4 urban referral hospitals in Zimbabwe from June 2014 to December 2015. Cervical biopsies were obtained for histology and HPV genotyping. HIV serology testing was performed. HPV testing was performed using MY09/MY11 polymerase chain reaction followed by typing using dot-blot hybridization. Results: Of 107 participants with histologically proven ICC, HIV prevalence was 49.5% (53/107). HIV-positive women tended to be younger (median age 44 years) than HIV-negative women (median age 59 years). HPV prevalence was 94% (101/107), ranging from 1 to 5 genotypes per participant. HPV 16 (81.5%), 18 (24%), 33 (13%), 35 (11%), 56 (9%), and 45 (7.4%) were the most prevalent genotypes among HIV-negative participants; HPV 16 (67.9%), 18 (43.4%), 56 (18.9%), 45 (15.1%), 33 (11.3%), and 58 (9.4%) were the most prevalent among HIV-positive participants. Eighty-three percent of women were infected with either HPV-16 or HPV-18. Conclusions: Effective vaccination programs against HPV 16 and HPV 18 could prevent up to 83% of cases of cervical cancer in Zimbabwe. HIV may influence distribution of some HPV genotypes given the significant increase in prevalence of HPV 18 among HIV-positive participants.

Background: Human papillomavirus (HPV) infection is now a well-established cause of cervical cancer and other anogenital cancers. An association between human immunodeficiency virus (HIV) infection and higher HPV incidence and prevalence are commonly reported. This study was conducted to demonstrate HPV prevalence, genotypes and its characteristics, according to the HIV status in women from Maputo in Mozambique. Methods: A total of 233 participants with ages ranging from fourteen to forty-five were included. Cervical samples were collected, DNA extracted, and HPV genotyping was performed using the HPV Direct Flow CHIP Kit. Results: In total, 177 HIV-negative and 56 HIV-positive women were included in the analysis. The overall HPV prevalence was 63% and was significantly higher among HIV-positive women (79% versus 58% among HIV-negative women; p = 0.005). The prevalence of multiple HPV type infections was 32%. High-risk HPV types 52, 68, 35, 18 and 16 were the most frequent. A higher proportion of HIV-positive women had multiple HPV types compared with HIV-negative women. Conclusions: This study demonstrated a high prevalence of HPV in the study cohort. HIV-positive women were identified as having the highest HPV prevalence and infection with multiple HPV types across all ages. High-risk genotypes were the most commonly found.

A subgroup of women who are co-infected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV), progress rapidly to cervical disease. We characterized HPV genotypes within cervical tumor biopsies, assessed the relationships of cervical disease stage with age, HIV-1 status, absolute CD4 count, and CD4 percentage, and identified the predictive power of these variables for cervical disease stage in a cohort of South African women.We recruited 181 women who were histologically diagnosed with cervical disease; 87 were HIV-1-positive and 94 were HIV-1-seronegative. Colposcopy-directed tumor biopsies were confirmed by histology and used for genomic DNA extraction. The Roche Linear Array HPV genotyping test was used for HPV genotyping. Peripheral whole blood was used for HIV-1 rapid testing. Fully automated FC500MPL/CellMek with PanLeucogate (PLG) was used to determine absolute CD4 count, CD4 percentage, and CD45 count. Chi-squared test, a logistic regression model, parametric Pearson correlation, and ROC curves were used for statistical analyses. We used the Benjamini-Horchberg test to control for false discovery rate (FDR, q-value). All tests were significant when bothPand q were <.05.Age was a significant predictor for invasive cervical cancer (ICC) in both HIV-1-seronegative (P < .0001, q < 0.0001) and HIV-1-positive women (P= .0003, q = 0.0003). Sixty eight percent (59/87) of HIV-1-positive women with different stages of cervical disease presented with a CD4 percentage equal or less than 28%, and a median absolute CD4 count of 400 cells/μl (IQR 300–500 cells/μl). Of the HIV-1-positive women, 75% (30/40) with ICC, possessed ≤28% CD4 cells vs 25% (10/40) who possessed >28% CD4 cells (bothP < .001, q < 0.001). Furthermore, 70% (28/40) of women with ICC possessed CD4 count >350 compared to 30% (12/40) who possessed CD4 count ≤ 350 (bothP < .001, q < 0.001).Age is an independent predictor for ICC. In turn, development of ICC in HIV-1-positive women is independent of the host CD4 cells and associates with low CD4 percentage regardless of absolute CD4 count that falls within the normal range. Thus, using CD4 percentage may add a better prognostic indicator of cervical disease stage than absolute CD4 count alone.

Six novel human papillomaviruses from penile swabs were characterised. Multiple full genome clones for each novel type were generated, and complete genome sizes were: HPV211 (7253bp), HPV212 (7208bp), HPV213 (7096bp), HPV214 (7357), HPV215 (7186bp) and HPV216 (7233bp). Phylogenetically the novel papillomaviruses all clustered with Gammapapillomaviruses: HPV211 is most closely related to HPV168 (72% identity in the L1 nucleotide sequence) of the Gamma-8 species, HPV212 is most closely related to HPV144 (82.9%) of the Gamma-17 species, HPV213 is most closely related to HPV153 (71.8%) of the Gamma-13 species, HPV214 is most closely related to HPV103 (75.3%) of the Gamma-6 species, HPV215 and HPV216 are most closely related to HPV129 (76.8% and 79.2% respectively) of the Gamma-9 species. The novel HPV types demonstrated the classical genomic organisation of Gammapapillomavirusess, with seven open reading frames (ORFs) encoding five early (E1, E2, E4, E6 and E7) and two late (L1 and L2) proteins. Typical of Gammapapillomavirusess the novel types all lacked the E5 ORF and HPV214 also lacked the E6 ORF. HPV212 had nine unique variants, HPV213 had five and HPV215 had four variants. Conserved domains observed among the novel types are the Zinc finger Binding Domain and PDZ domains. A retinoblastoma binding domain (pRB) binding domain in E7 protein was additionally identified in HPV214. This study expands the knowledge of the rapidly growing Gammapapillomavirus genus.

Background: Human papillomavirus (HPV) vaccination programs are a key intervention in protecting individuals against HPV-related disease. HIV1-infected individuals are at increased risk of HPV-associated cancers. This study was conducted to evaluate the potential role of prophylactic HPV vaccines in preventing new HPV infections among participants with perinatally acquired HIV who received the quadrivalent HPV vaccine at least five years before this study. Methods: This cross-sectional study was conducted at Newlands Clinic, Harare, Zimbabwe. The clinic provided the Gardasil quadrivalent HPV vaccine (4vHPV) to 624 adolescents living with HIV starting in December 2015. Vaginal and penile swabs were collected and tested for HPV types from the study participants who had received the 4vHPV vaccine 5–6 years before enrolment. Results: We present the results of 98 participants (44.6% female) vaccinated at a median age of 15 years (IQR 12–16). The mean amount of time since vaccination was 6 years (SD: ±0.4). The HPV-positive rate amongst the analyzed swabs was 69% (68/98). Among 30/98 (31%) HPV-positive participants, 13/98 (13%) had low-risk HPV types, and 17/98 (17%) had high-risk HPV types. Twelve participants tested positive for HPV18, only one participant tested positive for HPV16, and an additional four (4.3%) tested positive for either type 6 or 11, with respect to vaccine-preventable low-risk HPV types. Conclusion: The Gardasil quadrivalent HPV vaccine (4vHPV) was expected to protect against infection with HPV types 16, 18, 6, and 11. We demonstrated a possible waning of immunity to HPV18 in 17% of the participants, and an associated loss in cross-protection against HPV45. We observed a relatively high prevalence of ‘opportunistic non-vaccine HPV types’ or ‘ecological niche occupiers’ in this cohort, and suggest further research on the involvement of these types in cervical and other genital cancers. Our study is one of the few, if not the first, to report on HPV vaccine immunoprotection among people living with HIV (PLWH), thereby setting a baseline for further studies on HPV vaccine effectiveness among PLWH.