HPV-related Cervical Lesions Research Articles

Neutralizing antibodies against oncogenic human papillomavirus as a possible determinant of the fate of low-grade cervical intraepithelial neoplasia

To determine whether neutralizing antibodies (NAs) against HPV16 is responsible for a higher regression rate of low-grade cervical intraepithelial neoplasia (CIN1), we investigated an association between the presence of the NAs and the fate of the HPV16-related CIN1. All the women examined in this study had HPV16 positive cervix. The women were allocated into four groups by their cervical pathology, i.e., non-pathological (n:7), CIN1 (n:37), CIN2/3 (n:19), and cervical cancer (n:13). Their sera were tested for the presence of NAs against HPV16 by an in vitro assay using HPV16-pseudovirions. As for the CIN1 cases, clinical regression of the lesions were compared between NA-positive and NA-negative groups. Copy number of HPV16-DNA in smear samples was measured by quantitative PCR. The incidence of the presence of the NAs in the women with a non-pathological cervix (85.7%) was significantly higher than in the CIN1 cases (21.5%), the CIN2/3 cases (15.7%), and the cervical cancer cases (0%) ( p<0.0001). The regression of the CIN1 lesion was closely associated with the presence of the N As ( p=0.0002). The presence of the NAs was associated with low-level copy number of the viral DNA relative to the NA-negative group ( p=0.05). The presence of the NAs against HPV16 was associated with a higher regression rate of HPV-related CIN1 lesions. The NAs seem to have a role in deterring HPV-related cervical lesions from progressing to CIN2/3 by inhibiting the infection with de novo replicated HPV. This study further suggests that HPV vaccine to induce the NAs may be effective in eliminating CIN lesions, especially in the NA-negative cases.

Morphometric Characterization of HPV-Related Lesions of Uterine Cervix

This study addresses three issues related to human papillomavirus (HPV) cervical lesions: identification of HPV in histologic normal tissue, identification of HPV subtypes with risk for cervical cancer, and histologic differences between HPV not associated to cervical intraepithelial neoplasia (CIN1) lesions (condyloma) and HPV associated to CIN1 lesions. The authors histologically classified 48 cervical biopsy slides into three groups: normal (n = 22), condyloma (n = 20), and CIN1 (n = 6). Morphometric analyses of nuclear and cytoplasmic ratio for area, length, and diameter of 25 cells per case were performed. Histologic reports and in situ hybridization for HPV subtype were compared to morphometric data to assess correlation among them. Using image analysis, the authors correctly classified all cases except two into histologic or in situ hybridization diagnosis. Morphometry helped identify viral changes in cells that appeared histologically normal, HPV subtype at risk in condyloma lesions, and condyloma from those combining HPV lesions and CIN1. There were enough data supporting morphometric distinction of HPV-related cervical lesions assessed by nuclear and cytoplasmic ratio.

Morphometric Characterization of HPV-Related Lesions of Uterine Cervix

Objectives. This study addresses three issues related to human papillomavirus (HPV) cervical lesions: identification of HPV in histologic normal tissue, identification of HPV subtypes with risk for cervical cancer, and histologic differences between HPV not associated to cervical intraepithelial neoplasia (CIN1) lesions (condyloma) and HPV associated to CIN1 lesions. Materials and Methods. The authors histologically classified 48 cervical biopsy slides into three groups: normal (n = 22), condyloma (n = 20), and CIN1 (n = 6). Morphometric analyses of nuclear and cytoplasmic ratio for area, length, and diameter of 25 cells per case were performed. Histologic reports and in situ hybridization for HPV subtype were compared to morphometric data to assess correlation among them. Results. Using image analysis, the authors correctly classified all cases except two into histologic or in situ hybridization diagnosis. Morphometry helped identify viral changes in cells that appeared histologically normal, HPV subtype at risk in condyloma lesions, and condyloma from those combining HPV lesions and CIN1. Conclusions. There were enough data supporting morphometric distinction of HPV-related cervical lesions assessed by nuclear and cytoplasmic ratio.

P53 Codon 72 Polymorphism as a Risk Factor in the Development of HPV-Associated Cervical Cancer

Human papilloma virus (HPV) has been implicated in cervical carcinoma, and the p53 gene is polymorphic at amino acid 72 of the protein that it encodes. The association between p53 polymorphisms and risk for HPV-associated cervical cancer has been examined, but the results have been conflicting. It has been reported that patients with the arginine form have a higher risk of developing cervical cancer than those with the proline form. The purpose of this study was to examine whether p53 Arg at the polymorphic position 72 could represent a risk factor for women with high-risk HPV-associated premalignant and malignant cervical lesions. The study was carried out on 60 smears from patients with high-risk HPV-related cervical lesions. Also, 74 HPV-negative normal smears and 61 normal blood samples were used as controls. HPV-18 was the most frequent type. There was a difference in the distribution of p53 genotypes between high-risk HPV-cervical lesions and the normal samples. The allele frequency of p53 Arg/Arg was much higher than the normal samples (46.5% versus 20.5% in HPV-negative normal smears and 20% in blood samples). Based on the findings of this study, it is suggested that p53 Arg homozygosity could possibly represent a potential risk factor for the tumorigenesis of the cervix. Statistically significant correlation was not observed between the presence of Arg/Pro homozygosity or Arg/Pro heterozygosity and HPV typing.

Low false-negative rate of PCR analysis for detecting human papillomavirus-related cervical lesions.

Although PCR analysis is a sensitive test for detection of human papillomavirus (HPV) in the cervix, the proportion of cases of cervical dysplasia missed, or the false-negative rate, has been unknown. We determined the accuracy of PCR analysis for HPV DNA as a predictor of HPV-related cervical lesions in a cross-sectional study of sexually active women, aged 18 to 50 years, from the University of Michigan Family Medicine HPV study. Of 133 eligible participants, 41 underwent colposcopy because of a positive result for HPV of the cervix by the PCR method and 92 underwent screening colposcopy with biopsy prior to knowing the HPV PCR results. Twenty-four of those screened were subsequently found to also be HPV DNA positive. In those found to be HPV positive, histological studies revealed the presence of condyloma or cervical intraepithelial neoplasia in 16 women (24.6%) and changes suggestive of condyloma in 5 (7.6%). No HPV-negative woman had an abnormal biopsy or cytology report (P = 0. 000001). The false-negative rate (1 - sensitivity) for HPV PCR analysis for detection of the presence of a cervical HPV-related lesion was 0% (95% confidence interval, 0 to 0.047), and the specificity was 60.7%. In summary, PCR analysis for HPV DNA had a very low false-negative rate for predicting HPV-related lesions of the cervix in a community-based population. This supports the validity of using the absence of HPV at the cervix, as determined by PCR testing, as an inclusion criterion for patients in control groups in studies dealing with low-grade cervical lesions.

Antibodies prevalence against HPV-6b and -16 recombinant fusion proteins in Korean patients with cervical neoplasia.

This study was to investigate the adjunctive diagnostic utility of HPV fusion proteins from the sera in the patients with cervical neoplasia. Immunologic researches on host factors in HPV infection could contribute to better understanding of patho-physiologic mechanisms of cervical carcinogenesis, and provide valuable information for HPV vaccine development. Prevalence of antibodies against human papillomavirus (HPV) in sera of the patients with carcinoma (n = 81), precancers (n = 25) of uterine cervix and normal controls (n = 40) in Korean women were investigated by Western blot immunoassay using partially purified TrpE fusion recombinant proteins for HPV-6b and HPV-16. In 81 patients with cervical cancer, 15 (19%) and 54 (67%) patients were positive for antibodies to at least one of the tested recombinant proteins related to HPV-6b or HPV-16, respectively. And in 25 patients with HPV-related squamous intraepithelial lesion (SIL) of cervix, 10 were positive for at least one of the tested antibodies for HPV-6b gene products (40%) and 11 were positive for HPV-16 related antibodies (44%). The prevalence rates of antibodies for HPV-6b in the sera of SIL patients were significantly higher than those from the sera of cervical cancer patients (p < 0.05). There was an inverse correlation between increasing the positivity against HPV-16 E6 protein and progression of cervical lesions, but there was no significant correlation between the positivities of the other antibodies to HPV-16 and the severity of disease. These results suggest that the recombinant proteins related to HPV-6b and HPV-16 could be useful in evaluation of the patients with HPV-related cervical lesions and these might play an adjunctive role in diagnosis and management of cervical neoplasia.

Comparative DNA hybridization, cytology and histology of condylomatous and precancerous lesions of the cervix uteri

Cell scrapings from 552 consecutive women attending the colposcopy outpatient unit were examined by radioactive isotopic DNA hybridisation using the Dot-Blot technique, and by conventional Papanicolaou-smear cytology. In 315 out of these patients, punch biopsies were submitted for histological examination. HPV DNA-sequences were detected in 72% (n = 167) of 232 cytologically diagnosed CIN cases and in 77% (n = 97) out of 126 histological diagnoses of CIN. The proportion of HPV positive cases increased proportionally to the grade of CIN. The frequency of HPV type 6/11 decreased proportionally to the grade of the CIN, and HPV type 16/18 increased at the same time. The most frequent HPV type was 16/18 (26.3%), followed by the HPV types 31/33/35 (16.3%) and 6/11 (4.2%). Furthermore, HPV positivity was detected in 16.5% of patients with negative cytologic smears, in 21.7% of those with negative histology and in 8.9% of women with both negative histology and cytology. Histological and moreover cytological criteria of HPV infection decreased dramatically and proportionally inverse to the grade of the CIN. These changes were not followed entirely by HPV positivity. The discrepancy between HPV positivity (66.1%/67.6%) and morphological evidence of HPV infection (cytology 4.9%, histology 21.6%) was higher in CIN III than in lower grade CIN. Neither cytology nor histology is able to detect all HPV-related cervical lesions. Hybridisation techniques are helpful in the detection of latent HPV infections as well as of CIN lesions have been missed either by cytology or by histology or both. Thus both morphological methods are supplemented by HPV hybridisation.(ABSTRACT TRUNCATED AT 250 WORDS)