Summary In previous studies we have shown down-regulation of class I major histocompatibility complex (MHC) expression in a significant proportion of primary cervical carcinomas, which was found to be strongly correlated with loss of expression of the transporter associated with antigen presentation (TAP). By contrast, class II MHC expression was frequently up-regulated on neoplastic keratinocytes in these malignancies. In order to investigate whether these changes are associated with biological behaviour of the tumours, 20 cervical carcinomas were analysed for MHC (HLA-A, HLA-B/C, HLA-DR) and TAP-1 expression in the primary tumours and in lymph node metastases by immunohistochemistry. The results showed a significant increase in the prevalence of HLA-A and HLA-B/C down-regulation in metastasised neoplastic cells as compared with the primary tumour (P = 0.01). In all cases this was accompanied by loss of TAP-I expression. Up-regulated HLA-DR expression was found exclusively in primary tumours and was absent in the corresponding metastases (P= 0.002). These data are consistent with the hypothesis that loss of TAP-1 and the consequent down-regulation of class I MHC expression provides a selective advantage for neoplastic cervical cells during metastasis. Furthermore, the lack of class II MHC expression in metastasised cells either reflects a different local lymphokine production or indicates that these cells may have escaped CD4+ cytotoxic T-lymphocyte (CTL)-mediated killing.

A retrospective study of 227 patients presenting with abnormal cervical cytology was conducted to investigate the relationship between human papillomavirus (HPV) and progression of untreated cervical intraepithelial neoplasia (CIN) lesions. All patients had colposcopically directed biopsies for histologic diagnosis. The patients were followed cytologically and colposcopically for a mean of 19 months (range 6-42 months). Progression of a cervical lesion was defined as progression to a higher CIN grade confirmed histologically by directed biopsy. HPV DNA detection was done on material remaining from the cervical swabs by the general primer polymerase chain reaction (PCR) and type-specific PCR method, which made the detection of HPV types 6, 11, 16, 18, 31, 33 and not yet sequenced DNA types (X) possible. The presence of HPV DNA increased with the severity of the lesion (P < 0.001). In CIN III, a 100% HPV DNA prevalence was found, with HPV type 16 being the most prevalent type in 75%. Progression was significantly related to the presence of HPV DNA, in particular HPV type 16. The percentage of progressive disease was 21% in the case of HPV DNA positive lesions (n = 130) and 29% in the presence of HPV type 16, whereas HPV DNA negative lesions (n = 97) showed no progression. The detection of HPV DNA and HPV genotype can be used to identify patients with high-risk cervical lesions, since the presence of HPV DNA and genotype 16 in particular are closely related to CIN progression.

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Several prognostic factors in stages I B and II A cervical carcinoma have been widely studied to define groups of patients with a poor prognosis. Most of these factors are interrelated. The characteristics which should be regarded as main factors have not yet been defined, because the studies reported were based on mainly retrospective and non-randomized analysis. Reviewing the literature, lymph node metastasis, differentiation grade, tumor size, parametrial extension, lymphblood vessel invasion and cervical invasion seem to be prognostically important factors, which suggests that the subdivision of patients according to the FIG0 classification alone is inaccurate. It seems useful to define subgroups of patients according to tumor characteristics, determined after surgical treatment and accurate histologic examination of the surgical specimen. Patients with one or more of these tumor features need additional treatment to improve survival. The current treatment modalities, such as postoperative radiotherapy, have not been thoroughly evaluated, but doubt exists as to their efficacy. Data in the literature suggest that particularly patients with para-aortic or multiple pelvic lymph node metastasis (> 3) have already developed distant metastases at the time of primary treatment and therefore need adjuvant systemic therapy. Patients with tumors larger than 4 cm in diameter, differentiation grade III, lymph-blood vessel invasion or cervical invasion (of more than 70%) seem to have high recurrence rates at both pelvic and distant sites, indicating that there is also a need for better pelvic control.