Platinum-based adjuvant chemotherapy improved overall survival and recurrence-free survival at 5 years in this combined group of patients with early-stage ovarian cancer defined by the inclusion criteria of the ICON1 and ACTION trials.

HLA-E is a nonclassical HLA class I molecule, which differs from classical HLA molecules by its nonpolymorphic, conserved nature. Expression and function of HLA-E in normal tissues and solid tumors is not fully understood. We investigated HLA-E protein expression on tissue sections of 420 ovarian and cervical cancers and found equal or higher levels than normal counterpart epithelia in 80% of the tumors. Expression was strongly associated with components of the antigen presentation pathway, e.g., transporter associated with antigen processing (TAP), endoplasmic reticulum aminopeptide (ERAP), β2 microglobulin (β2m), HLA classes I and II, and for ovarian cancer with tumor infiltrating CD8 + T lymphocytes (CTLs). This association argues against the idea that HLA-E would compensate for the loss of classical HLA in tumors. In situ detection of HLA-E interacting receptors revealed a very low infiltrate of natural killer (NK) cells, but up to 50% of intraepithelial CTLs expressed the inhibiting CD94/NKG2A receptor. In cervical cancer, HLA-E expression did not alter the prognostic effect of CTLs, most likely due to very high infiltrating CTL numbers in this virus-induced tumor. Overall survival of ovarian cancer patients, however, was strongly influenced by HLA-E, because the beneficial effect of high CTL infiltration was completely neutralized in the subpopulation with strong HLA-E expression. Interestingly, these results indicate that CTL infiltration in ovarian cancer is associated with better survival only when HLA-E expression is low and that intratumoral CTLs are inhibited by CD94/NKG2A receptors on CTLs in the tumor microenvironment.

Purpose: Therapeutic vaccination with human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides (SLP) is effective against HPV16-induced high-grade vulvar and vaginal intraepithelial neoplasia (VIN/VaIN). However, clinical nonresponders displayed weak CD8 þ T-cell reactivity. Here, we studied if imiquimod applied at the vaccine site could improve Results: Forty-three patients were assigned to either ISA101 with imiquimod (n ¼ 21) or ISA101 only (n ¼ 22). Imiquimod did not improve the outcomes of vaccination. However, vaccineinduced clinical responses were observed in 18 of 34 (53%; 95% CI, 35.1-70.2) patients at 3 months and in 15 of 29 (52%; 95% CI, 32.5-70.6) patients, 8 of whom displayed a complete histologic response, at 12 months after the last vaccination. All patients displayed vaccine-induced T-cell responses, which were significantly stronger in patients with complete responses. Importantly, viral clearance occurred in all but one of the patients with complete histologic clearance.Conclusions: This new study confirms that clinical efficacy of ISA101 vaccination is related to the strength of vaccine-induced HPV16-specific T-cell immunity and is an effective therapy for HPV16-induced high-grade VIN/VaIN.

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Improvement in systemic antitumor responses is needed before this approach can prove useful as adjunctive treatment following induction chemotherapy in patients with minimal residual disease.

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The focus of this study was to document postoperative complications after vulvectomy and inguinofemoral lymphadenectomy using separate incisions. Data from 172 consecutive patients with newly diagnosed carcinoma of the vulva were studied. One hundred and one patients primarily treated with modified radical vulvectomy and complete inguinofemoral lymphadenectomy using separate groin incisions (n = 187) were included in this study. One or more complications were documented in 77 of the 101 (76%) patients. Complications after groin dissection were observed in 66% of the patients. The main complications were wound breakdown (17%) and/or infection (39%) of the groin, lymphocyst formation (40%), and lymphedema (28%). In 98 of 187 (52%) groin dissections, one or more complications were documented. The presence of lymph node metastases, postoperative radiation, age older than 65 years, and removal of the vena saphena magna were not significant risk factors for the occurrence of complications. The occurrence of early complications after groin dissection was significantly related to the late-complication lymphedema (P = 0.002). Our results confirm relatively high rates of wound breakdown, infection, lymphocyst formation, and lymphedema even with separate groin incisions. The occurrence of early complications was related to lymphedema. No other risk factors could be identified.