Data on human papillomavirus (HPV) type-specific cervical cancer risk in women living
with human immunodeficiency virus (WLHIV) are needed to understand HPV–HIV interaction and to
inform prevention programs for this population. We assessed high-risk HPV type-specific prevalence
in cervical samples from 463 WLHIV from South Africa with different underlying, histologically
confirmed stages of cervical disease. Secondly, we investigated DNA hypermethylation of host
cell genes ASCL1, LHX8, and ST6GALNAC5, as markers of advanced cervical disease, in relation
to type-specific HPV infection. Overall, HPV prevalence was 56% and positivity increased with
severity of cervical disease: from 28.0% in cervical intraepithelial neoplasia (CIN) grade 1 or less
( CIN1) to 100% in invasive cervical cancer (ICC). HPV16 was the most prevalent type, accounting
for 9.9% of HPV-positive CIN1, 14.3% of CIN2, 31.7% of CIN3, and 45.5% of ICC. HPV16 was
significantly more associated with ICC and CIN3 than with CIN1 (adjusted for age, ORMH 7.36
(95% CI 2.33–23.21) and 4.37 (95% CI 1.81–10.58), respectively), as opposed to non-16 high-risk HPV
types. Methylation levels of ASCL1, LHX8, and ST6GALNAC5 in cervical scrapes of women with
CIN3 or worse (CIN3+) associated with HPV16 were significantly higher compared with methylation
levels in cervical scrapes of women with CIN3+ associated with non-16 high-risk HPV types (p-values
0.017, 0.019, and 0.026, respectively). When CIN3 and ICC were analysed separately, the same trend
was observed, but the differences were not significant. Our results confirm the key role that HPV16
plays in uterine cervix carcinogenesis, and suggest that the evaluation of host cell gene methylation
levels may monitor the progression of cervical neoplasms also in WLHIV.
Van Zummeren, Marjolein; Kremer, Wieke W.; Van Aardt, M.C. (Matthys Cornelis); Breytenbach, Erika; Richter, Karin Louise; Rozendaal, Lawrence; Witte, Birgit I.; De Strooper, Lise M.A.; Hesselink, Albertus T.; Heideman, Danielle A.M.; Snijders, Peter J.F.; Steenbergen, Renske D.M.; Dreyer, Greta; Meijer, Chris J.L.M.(Lippincott Williams and Wilkins, 2017-09)
OBJECTIVE : Cervical cancer is the leading cause of cancer-related death in women in South Africa. This study evaluates DNA methylation levels in cervical (pre)cancer and aims to assess the value of high-risk human ...
HIV-related immunodeficiency has complex effects on female genital HPV, which include increased risks of infection, multiple types, persistence, reactivation and the risk to develop pre-invasive and invasive disease.
More than 40 genital types of HPV have been identified, of which 15 are known to be oncogenic. High risk HPV types cause all cervical cancers and true cervical pre cancer lesions, including cervical intra epithelial neoplasie ...