Specificity of L1 Peptides versus Virus-Like Particles for Detection of Human Papillomavirus-Positive Cervical Lesions in Females Attending Engativa Hospital, Bogota, Colombia

Abstract

A serological test for the detection of human papillomavirus (HPV) infection in females at risk of developing cervical cancer could be based on conserved L1 peptides with low levels of antigenicity specifically recognized by antibodies from patients with cervical lesions infected with high-risk HPV (HR-HPV) types. The aim was to assess the ability of L1 peptides 18283, 18294, and 18301 compared with the ability of virus-like particles (VLPs) to identify these infections in females. A total of 391 HPV-infected female volunteers were interviewed, and peripheral blood and cervical cells were obtained for detection of anti-HPV antibodies and HPV DNA; all of the patients had a Pap smear test; 287 patients were referred for colposcopy or biopsy, according to gynecological criteria. The level of agreement, as determined by the use of the Lin coefficient (rho value), showed that 75 to 83% of females with HR-HPV DNA-positive cervical lesions had antibodies that recognized VLPs and peptide 18283, 18294, or 18301, while 15 to 23% of the HPV DNA-negative females with a normal cytology had antibodies that recognized these three peptides and 45% had antibodies that recognized VLPs. The rate of agreement between peptides and VLPs for antibody detection was higher for patients with HPV DNA-positive cervical lesions. Peptides 18283, 18294, and 18301 showed similar sensitivities for the detection of HR-HPV DNA-positive cervical lesions and were more specific than VLPs. Peptide 18301 might be detecting protective antibodies in HPV DNA-negative females with atypical squamous cells of undetermined significance. These peptides could be useful for the design of a serology test for the detection of HR-HPV infection in females with cervical lesions and at risk of cervical cancer.More than 100 human papillomavirus (HPV) types infect human tissues; 40 of these types of viruses (named high-risk HPV [HR-HPV] types) are able to induce carcinomas such as cervical cancer (3, 23). About 70% of females become infected with HPV within the 2 years following the start of sexual activity (22,37), and 90% of these females have transient HPV infections (2, 13). Cervical lesions caused by persistent HPV infection are detected in about 5% of females; some of these can progress to cervical cancer. Seventy to 90% of HPV-infected females seroconvert 6 to 18 months after HPV DNA is detected, but this rarely occurs in females with transient HPV infection (1,4,25).There is a relationship between a high viral load and the progression of cervical lesions and cervical cancer (13, 27). The anti-HPV antibody response is correlated with the viral load (11, 36). Most potentially oncogenic, persistent, long-term HPV infections elicit an antibody response which can be detected by using virus-like particles (VLPs) (5,20). In fact, the anti-VLP antibody response is stable; is related to persistent infection, the viral load, and neoplastic lesion development; and is rarely found in patients with transient HPV infections (10,16,25,29).Seropositivity for VLPs seems to be a...

Age-Specific Human Papillomavirus Antibody and Deoxyribonucleic Acid Prevalence: A Global Review

“…Central and South American seroprevalence data were available for women from Argentina (16), Brazil (109-111), Colombia (111-115), and Costa Rica (116,117) (Supplementary Figure 1I-J). No data on HPV seroprevalence in children and adolescents under age 15 were available (16).…”

Differential Antibody Response against Conformational and Linear Epitopes of the L1 Proteins from Human Papillomavirus Types 16/18 Is Observed in Vaccinated Women or with Uterine Cervical Lesions

“…For instance, in the Wang SS and colleagues study [ 33 ], it was shown that the anti-VLPs HPV16/18 antibodies were strongly associated with the HPV DNA-positive CIN3/cancer women group (OR = 34.7 and 16.6, respectively), but the associations dropped drastically when only the presence of anti-VLPs HPV16/18 antibodies were considered in the statistical analysis (OR = 2.0 and 1.9, respectively) [ 33 ]. In contrast, Urquiza and colleague’s study [ 18 ] showed that antibodies against three L1 peptides from HPV16 were more sensitive than anti-VLPs antibodies for the detection of HPV DNA-positive cervical lesions [ 18 ]. Our results are in agreement with both studies, as we observed a similar low association for anti-VLPs-16 antibodies in the CIN3/CC group (OR = 2.29), as in the Wang report when the HPV DNA status was not considered in the analysis.…”

“…For instance, by using and ELISA-VLPs for HPV16, the prevalence range was from 7% to 43% in healthy women, from 25% to 68% among women with CIN lesions, and from 28% to 100% among women with CC [ 14 , 15 , 21 , 23 , 40 ]. When the L1 protein from HPV16 was used in the ELISA (linear L1 or recombinant GST-L1), the prevalence varied from 3% to 52% in healthy women, from 10% to 95% in CIN lesions, and from 21% to 100% in CC [ 17 , 18 , 41 , 42 ]. The variability in the ELISA results could be due to differences in the antigen preparations (VLPs or L1) used by each laboratory.…”

“…Based on the results from these systems, several groups have reported a high prevalence of these antibodies in patients with low-grade lesions (~60%), which increases with the severity of the uterine cervical lesion [ 16 , 17 , 18 ]. A low prevalence of anti-L1 antibodies has also been reported among healthy women (<25%), which may point to previous HPV infections [ 17 , 18 , 19 , 20 ]. Recently, the generation of VLPs in baculovirus and yeast has allowed the measurement of neutralizing antibodies, as well as of antibodies against conformational epitopes [ 20 ].…”

“…These VLPs have been used in epidemiological studies to characterize the anti-VLPs immune response in different female populations, such as women from the general population, women with precancerous lesions, or those with CC [ 16 ] and, more recently, to evaluate the efficacy of the HPV vaccines [ 9 , 10 , 11 , 21 ]. Using the ELISA system for VLPs or denatured L1 antigens, several groups showed an antibody prevalence ranging from 7% to 43% in healthy women [ 14 , 18 , 21 , 22 ], from 25% to 65% in women with CIN 1–3 lesions [ 14 , 18 , 21 , 23 ], and from 43% to 100% in CC patients [ 23 , 24 , 25 ]. Although these results are heterogeneous, a constant was that both types of antibodies (anti-L1 and anti-VLPs) increased with the severity of the cervical lesion.…”