The Clinical Significance Of P16, PR Expression And HPV Detection In Various Subtypes Of Cervical Adenocarcinoma

ObjectionThe aim of the study was to analyze the relations of the histological subtypes, the expression of p16/PR, the prevalence of HPV and the prognosis for invasive cervical adenocarcinoma.Methods108cases of cervical adenocarcinoma were classified according to the World Health Organization (WHO) and other associated literatures. The immunohistochemistry study was performed to analyze the expression of pl6/PR in cervical adenocarcinoma. The detection of HPV-DNA was established by PCR. The detailed clinical information was obtained by the review of related medical records and the prognosis was analyzed by contacting the patients.Results(1) The108cases of invasive cervical adenocarcinoma applied into this study were composed of endocervical type (n=27,25%), intestinal type (n=19,17.6%), endometrioid type (n=18,16.7%), adenosquamous type (n=9,8.3%), gastric type (n=8,7.4%), minimal deviation type (n=7,6.5%), clear cell type (=6,5.5%), signet-ring cell type (n=5,4.6%), villoglandular type (n=5,4.6%), glassy cell type (n=2,1.9%), mesonephric type (n=1,0.9%) and carcinosarcoma (n=1,0.9%).(2) The overall positive rate of p16was86.1%in cervical adenocarcinomas. Among all the cases, the intestinal, endometrioid and clear cell types shared the highest p16positive rate of more than90%, whereas the gastric and minimal deviation types ranked the least positive rate of less than60%. The difference of p16expression was analyzed and showed statistical significance (p<0.05).The overall positive rate of PR was20.4%. PR expression rate of66.7%in endometrioid type forms sharply contrast to no positivity in gastric, minimal deviation, signet-ring cell, clear cell, mesonephric and carcinosarcoma types, the difference of which showed statistical significance (p<0.05).(3) The overall prevalence of HPV infection in cervical adenocarcinoma was71.3%. The highest HPV infection rate was detected in intestinal and adenosquamous cases, with the rate of89.5%and100%respectively. By contrast, the gastric type and minimal deviation type showed the lowest HPV infection rate of25%and42.9%respectively. The HPV infection rate was analyzed and showed statistical significant difference (p<0.05). HPV18was the most common type, followed by HPV16. The infection of16and18accounted for74%of HPV positive cases.(4) Diffuse p16expression was shown in87.5%of HPV positive cases, while in23.8%of HPV negative cases, with statistical significant difference (p<0.05).(5)71cases were treated, including5cases of pure radiotherapy and or chemotherapy,16pure surgery,50surgery plus adjuvant treatment. The follow-up information was obtained in66cases with7.0%of lost-to-follow-up. Kaplan-Meier method analysis demonstrated that the clinical stage, the histological subtype and the expression level of p16were significantly correlated with the survival of cervical adenocarcinoma (p<0.05). Cox proportional hazard regression model multivariate analysis revealed both the clinical stage and p16as independent factors that related to the prognosis of cervical adenocarcinoma (p<0.05).Conclusions1. Among all the subtypes, the endocervical type, intestinal type, the endometrioid type and the adenosquamous type are more common in cervical adenocarcinoma.2. Diffuse p16expression always relates with HPV infection. And PR positivity may be co-related with endometrioid differentiation.3. Most cases of cervical adenocarcinoma associate with HPV infection, whereas the gastric and minimal deviation types show lower positive rates.4. HPV16and18are the predominant types. Comparing to cervival squamous-cell carcinoma, HPV18shows a stronger association with cervical adenocarcinoma.5. The expression level of p16is an independent prognostic factor in cervical adeoncarcinoma.