The impact of HPV-specific infection in women diagnosed with atypical glandular cells: Results from the HPV-AGC study.

OBJECTIVE: To evaluate the impact of various HPV types on the risk of developing lesions of the uterus (either uterine cervix and endometrium) in women diagnosed with "atypical glandular cells" (AGC) at Pap smear. METHODS: This is a multi-institutional retrospective study. Data of women diagnosed with AGC were retrospectively reviewed. All patients included had data about HPV DNA testing and 1-year clinical follow-up. RESULTS: Overall, chart of 480 patients were evaluated. After the exclusion of 286 patients, data of 194 patients were available for the analysis. Mean age was 43.9 (±6.0) years. HPV infection was documented in 136 women (70.1 %). Among HPV positive patients the risk of having/developing a lesion was 33.8 % (n = 46). Lesions included low- (L-SIL) and high- (H-SIL) squamous intraepithelial lesions, in situ adenocarcinoma of the uterine cervix, invasive cancer of the uterine cervix, endometrial hyperplasia and endometrial cancer in 16 (11.7 %), 18 (13.2 %), 6 (4.4 %), 3 (2.2 %), 2 (1.5 %) and 1 (1%), respectively. Among HPV negative patients the risk of having/developing a lesion was 15.5 %. They included l-SIL, H-SIL, in situ adenocarcinoma, endometrial hyperplasia and endometrial cancer in 1 (1.7 %), 1 (1.7 %), 1 (1.7 %), 3 (5.1 %) and 3 (5.1 %), respectively. Patients diagnosed with HPV16 were at higher risk of having/developing cervical lesions in comparison to patients with other HPV infections (p < 0.01). In comparison to other HPV types, the presence of HPV 18, 31, 33, and 45 did not increase the risk of developing a lesion over the time (p > 0.2). HPV positive patients were at higher risk of being diagnosed with a cervical lesion within 6 months from detection of AGC. CONCLUSIONS: Patients diagnosed with AGC are at risk to have / developing cervical and uterine lesions. Further prospective evidence is needed.

[Detection rates of various serotypes of human papilloma virus in atypical glandular hyperplasia and adenocarcinoma of the endometrium and their immunomorphological features in virus-positive cases].

Various virus serotypes were found in 35.3% of cases and their detection rate frequency reducing with age. They were detectable in 35.3 -52.9% of cases of atypical glandular hyperplasia, highly and moderately differentiated adenocarcinoma of the endometrium and only in 17.6% of cases of poorly differentiated adenocarcinomas. Serotypes 58 and 51 were nearly twice more frequently, but serotypes 18 and 52 were not observed. Immunomorphologically virus-positive observations were characterized by pronounced infiltration with T-helper and T-suppressor/killer cells. The endometrium and tumors showed an increased significant proliferative activity (Ki-67 expression) and reduced expression of receptors to progesterone and, to a lesser degree, to estrogen in 47-83% of virus-positive cases. Expression of growth factors did not greatly differ.

Association of human papillomavirus with malignant and premalignant lesions of the uterine endometrium.

The possible association of human papillomavirus (HPV) with endometrial hyperplasia and endometrial adenocarcinoma was investigated. DNA from frozen tissues of 30 endometrioid carcinomas of Japanese patients was tested for HPV DNA by Southern blot hybridization analysis. Screening with HPV type 58 probe under low stringency conditions showed the presence of HPV DNA in two of 30 endometrioid carcinomas. High stringency hybridization identified HPV type 16 in the two positive specimens. The presence of HPV was further analyzed by polymerase chain reaction (PCR)-Southern blot analysis of DNA from archival tissue blocks of the initial 30 endometrioid carcinomas as well as an additional 17 endometrioid carcinomas and 13 atypical hyperplasias of the endometrium from Japan and 38 endometrioid carcinomas from the United States. Polymerase chain reaction amplification using type 16-specific HPV primers for a portion of the E6 open reading frame was positive in six of 47 (13%) endometrioid carcinomas from Japan, including two in which HPV 16 was not detected by Southern blot analysis and two of 38 (5%) endometrioid carcinomas from the United States. Polymerase chain reaction amplification using L1 consensus sequence primers was positive for HPV in two of 13 (15%) endometrial hyperplasias, 13 of 47 (28%) endometrioid carcinomas from Japan, and six of 38 (16%) endometrioid carcinomas from the United States. Slot blot hybridization identified HPV type 16 in seven of the L1 PCR products, including all but one specimen testing positive for HPV type, 16 using E6 type specific primers. In situ hybridization was positive for HPVs 16/18 in glandular epithelial tumor cells in six of the PCR-positive specimens. An additional specimen showed staining for HPVs 16/18 in acellular luminal debris in association with squamous metaplasia of the tumor, but staining was negative in the glandular cells of the tumor. Human papillomavirus was not detected by in situ hybridization in the remaining specimen, which was PCR positive for HPV 16. In situ hybridization was weakly positive for HPVs 31/33/35 in one specimen and was weakly positive for HPVs 6/11 in benign endometrial epithelial cells but not in tumor cells of another specimen that tested positive for HPV by L1 PCR. Two dimensional gel electrophoresis performed on two specimens showed that HPV DNAs were integrated into cellular DNA with no episomal coexistence. These findings suggest that HPV, especially HPV 16, may play an etiologic role in a fraction of endometrioid adenocarcinomas.