HPV types 16/18 L1 E6 and E7 proteins seropositivity and cervical cancer risk in HIV-positive and HIV-negative black South African women

Abstract

Background In populations with high rates of human immunodeficiency virus (HIV)-coinfection, the nature of the relationship between human papillomavirus (HPV)-16 and -18 (L1, E6 and E7) antibodies and cervical cancer is still uncertain. We measured the association between seropositivity to HPV (L1, E6 and E7) proteins and cervical cancer among black South African women with and without HIV co-infection. Methods We used questionnaire data and serum collected from consecutively recruited patients with a newly diagnosed cancer from the Johannesburg Cancer Study from 1346 cervical cancer cases and 2532 controls (diagnosed with other non-infection related cancers). Seropositivity to HPV proteins was measured using a multiplex serological assay based on recombinant glutathione S-transferase (GST) fusion proteins. We measured associations between their presence and cervical cancer using unconditional logistic regression models and evaluated the sensitivity and specificity of these HPV biomarkers. Results Among controls, HIV-negative women from rural areas compared to urban had significantly higher HPV seroprevalence, HPV16 E7 (8.6% vs 3.7%) and HPV18 E7 (7.9% vs 2.0%). HPV16 E6 and E7 antibodies were positively associated with cervical cancer in HIV-positive (Adjusted Odds Ratio (AOR) = 33; 95% CI 10–107) and HIV-negative women (AOR = 97; 95% CI 46–203). In HIV-positive women, HPV E6/E7 antibodies had low sensitivity (43.0%) and high specificity (90.6%) for cervical cancer detection. In HIV-negative women, HPV E6/E7 antibodies sensitivity was 70.6% and specificity was 89.7%. Conclusions Our data show that HPV (L1, especially E6 and E7) antibody positivity is associated with cervical cancer in both HIV-positive and HIV-negative women. Nonetheless, being HIV-positive plays an important role in the development of cervical cancer.

Antibodies against high‐risk human papillomavirus proteins as markers for noncervical HPV‐related cancers in a Black South African population, according to HIV status

“…29 For our study, and after excluding cancers without serum samples, we included a total of 535 noncervical HPV-related cases, con- The JCS is amenable to a case-control study design and analysis, where the selection of cancer controls can be used to examine exposures of interest. 9 During the same period, after excluding other infection-related cancers (including 4306 cervical cancers for which HPV serology results have been reported previously), 9 10,397 participants with non-infection-related cancers were recruited in the JCS (the distribution of the cancers are in Supplementary Table S2). Of these 10,397 participants with non-infection-related cancers, 6651…”

“…4 It can also influence the proportion of noncervical cancers attributable to HPV, [5][6][7][8] but it may also influence the immune response to HPV proteins. 9 Different HPV proteins are expressed during the development process toward HPV-related malignancy and can produce antibody responses. The late protein L1 forms the virus capsid, and antibodies against HPV L1 are considered markers of cumulative exposure to the virus, even though many HPV-infected women are known to not seroconvert.…”

“…10 Early HPV oncoproteins E6 and E7 interact with cellular proteins involved in cell cycle control and DNA repair, most notably p53 and pRb, and are implicated in malignant cellular transformation. Indeed, antibodies against E6 of HPV16 and HPV18 have been found to be highly specific markers of cervical cancer in comparison to controls, [9][10][11][12][13] as well as of oropharyngeal cancer. [14][15][16][17][18] However, there remains a limited understanding of E6 and E7 antibodies as potential biomarkers for other HPV-related cancers, [19][20][21][22][23] which were performed in European or North American populations only.…”

Seroprevalence and Molecular Investigation of Human Papillomavirus (HPV) Type-16 in HIV Positive Women in Abakaliki, Nigeria

“…Genes E6 and E7 of the HPV-16 encode the two major oncoproteins E6 and E7, which are required for cell cycle transformation and virus immune system evasion of the infecting organism 7 . The HPV-associated cancers are usually common amongst patients 8,9 . It is therefore important to screen for HPV strains as a routine to guide therapy in such individuals in order to control the evolution and transmission of the virus in human population.…”

Dihydromyricetin Inhibited Migration and Invasion by Reducing S100A4 Expression through ERK1/2/β-Catenin Pathway in Human Cervical Cancer Cell Lines

“…It has two histological types, adenocarcinoma (AC) and squamous cell carcinoma (SCC) [ 1 ], of which SCC accounts for 70% of diagnoses [ 3 ]. Human papillomavirus (HPV) infection plays a primary role in cervical cancer [ 4 ]. HPV causes approximately 90–100% of cervical cancer cases, especially in patients aged <35 years [ 5 ].…”