In women with abnormal smears (cervical intraepithelial neoplasia [CIN] I, II, and III and invasive cancer) HPV infection was detected in 35-40%; this rate seemed to be age-independent. the Peak incidence of CIN appeared several years after that of HPV infection.
None of the cervical intraepithelial neoplasia grade I (CIN I) contained HPV 16 while 50% of the CIN III lesions (carcinoma in situ, CIS) contained HPV 16.
Either HPV infection or accumulation of p53 was found in 16.7% (5/30) of the cases of normal or metaplastic cervix, 29.4% (5/17) of CIN I, 45.0% (9/20) of CIN II, 86.5% (32/37) of CIN III and 87.0% (20/23) of ISCC cases.
Here, we demonstrate that high-grade dysplasia (CIN III, n = 9) completely lacks both MCP-1 expression and CD68+-macrophage infiltration, while MCP-1-specific signals were occasionally detectable in one out of 5 CIN-II and in one out of 3 CIN-I lesions.
Archival cervical biopsy specimens (n = 107) of normal squamous epithelia (n = 18), pure HPV squamous epithelial lesions (n = 15), cervical intraepithelial neoplasia (CIN) I lesions (n = 17), CIN II lesions (n = 26), and CIN III lesions (n = 31) underwent bcl-2 immunohistochemical analysis with use of the streptavidin-biotin complex/horseradish peroxidase system and nonisotopic in situ hybridization for the detection of HPV DNA.
We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects.
The overall HPV positive rate was 44.3% with 18.6% (16/86) for normal/inflamed cervices, 36.4% (32/88) for condyloma, 64.7% (33/51) for cervical intraepithelial neoplasia grade 1 (CIN 1), 37.9% (11/29) for CIN 2, 68.3 (41/60) for CIN 3, and 77.8% (14/18) for carcinoma.
The data indicate that E2 protein expression is highest in koilocytes in lower-grade CIN (I), but decreases with increasing grade, whereas the detection of HPV DNA is delayed until CIN I/II, rising to the highest levels in carcinoma cells.
Interestingly, MPG expression in CIN III and invasive carcinoma (IC) was much higher than normal and CIN I. Granular positivity of MPG was notable in the perinuclear regions of the cytoplasm in HPV-infected invasive cancer.
Immunohistochemical analysis of cervical tissue specimens showed a clear nuclear staining for GATA-3 in normal cervical squamous epithelium (n = 14) and all cervical intraepithelial neoplasia (CIN) I (n = 6) and CIN II lesions (n = 2).
A significant statistical relationship was found between Fhit protein expression and HPV 16 infection in combined CIN1, CIN3, and MICA cases (P = <0.001).
In those women referred with persisting borderline or mildly dyskaryotic smears, those who had histologically proven underlying CIN II/III, had statistically significant higher Brn-3a levels than those with a similar smear but histologically shown to have HPV, CIN I, or no cervical abnormality.
We detected TSLC1 promoter hypermethylation in seven (35%, 95% CI = 15% to 59%) of 20 high-grade CIN lesions (i.e., CIN II and III) and in 30 (58%, 95% CI = 43% to 71%) of 52 cervical squamous cell carcinomas compared with none (0%, 95% CI = 0% to 34%) of nine normal cervical epithelial biopsy samples and none (0%, 95% CI = 0% to 22%) of 12 CIN I lesions (P<.001 for cervical squamous cell cancer versus normal epithelial biopsy samples plus CIN I lesions).
None of 20 non-neoplastic cervices showed p16 INK4A and MGMT gene hypermethylation, whereas at least one of these genes was hypermethylated with 50.0% (5/10) of CIN I, 65.0% (13/20) of CIN II-III, 70.2% (33/47) of SCC and 85.0% (17/20) of adenocarcinoma. p16 INK4A protein was totally negative in non-neoplastic cervices, but positive with 90.0% of CIN I, 100% of CIN II-III and adenocarcinoma, and 78.7% of SCC.
None of 20 non-neoplastic cervices showed p16 INK4A and MGMT gene hypermethylation, whereas at least one of these genes was hypermethylated with 50.0% (5/10) of CIN I, 65.0% (13/20) of CIN II-III, 70.2% (33/47) of SCC and 85.0% (17/20) of adenocarcinoma. p16 INK4A protein was totally negative in non-neoplastic cervices, but positive with 90.0% of CIN I, 100% of CIN II-III and adenocarcinoma, and 78.7% of SCC.