Clinicopathological features and programmed death-ligand 1 immunohistochemical expression in a multicenter cohort of uterine and ovarian melanomas: a retrospective study in Japan (KCOG-G1701s).

The objective of this study was to propose prognostic factors and optimal treatment strategies by analyzing the clinicopathological features and programmed death-ligand 1 (PD-L1) expression. We analyzed 31 patients diagnosed with uterine or ovarian melanoma between 1997 and 2017 in the Kansai Clinical Oncology Group/Intergroup. Twenty-four and seven patients with cervical and ovarian melanomas were included, respectively. Immune checkpoint inhibitors were used in seven patients, and the objective response rate was 40%. Notably, two patients with objective responses had a high PD-L1 expression. Ten and four patients with cervical and ovarian melanomas, respectively, had high PD-L1 immunohistochemical expressions. Multivariate analysis revealed that tumor stage was an independent prognostic factor for progression-free survival in patients with cervical melanomas. In patients with ovarian melanomas, the 1-year cumulative progression-free and overall survival rates were 0 and 29%, respectively. Kaplan-Meier analyses revealed that age <60 years was associated with poorer progression-free and overall survivals in patients with ovarian melanomas. In patients with cervical melanomas, the 1-, 3-, and 5-year cumulative overall survival rates were 53, 32, and 16%, respectively. Histological atypia was associated with a poorer progression-free survival, but there was no difference in survival between patients who underwent radical hysterectomy and those who did not. The present study is a large cohort study of uterine and ovarian melanomas, which are aggressive tumors with a significantly poor prognosis, even after standard surgery and adjuvant therapy. The use of immune checkpoint inhibitors is a promising and effective treatment option.

Rupture of a dissecting thoracoabdominal aortic aneurysm due to Citrobacter freundii infection.

We describe a case of an elderly man with Citrobacter freundii-associated infectious rupture of a dissecting thoracoabdominal aortic aneurysm. We performed an emergency thoracoabdominal aortic replacement using a rifampicin-soaked prosthetic graft and omental flap wrapping. The patient was discharged on postoperative day 255, although he experienced pseudomembranous enteritis and paraplegia.

Dual aortic aneurysms with coronary artery and multiple cerebrovascular stenoses.

Total debranching thoracic endovascular aortic repair is useful for avoiding neurological complications in cases where cardiopulmonary bypass is difficult and for devising an intraoperative cervical branch reconstruction method.

Treatment-related leukemia after taxane and platinum therapy in gynecological cancer patients (Gynecologic Oncology Trial and Investigation Consortium 011).

AIM: To clarify incidence and clinical features of treatment-related leukemia (TRL) due to taxane/platinum therapy in gynecological cancer patients. METHODS: We conducted a retrospective study of gynecological cancer patients who were diagnosed at facilities participating in the Gynecologic Oncology Trial and Investigation Consortium and started only taxane/platinum therapy as chemotherapy between 2002 and 2006. RESULTS: The site of the primary lesion was the ovary in 124, endometrium in 37, and uterine cervix in 4. The regimen of chemotherapy was paclitaxel (T) + carboplatin (C) therapy in 134 and others in 31 patients. The cumulative incidence was 2.4% (4/165), and the incidence was 2.9/1,000 person-years. All four cases were acute myeloid leukemia. The average total doses of T and C in patients without TRL were 1,693 (SD 1,050) and 4,170 (SD 2,423) mg. For TRL patients, the total T and C doses were, respectively, 1,555 and 3,540 mg, 1,620 and 4,200 mg, 2,130 and 4,700 mg, 3,220 mg and 8,310 mg. The fourth patient received additional 2,415 mg of docetaxel and 2,155 mg of nedaplatin. The intervals from the primary chemotherapy to the onset of TRL were 27, 34, 67, and 114 months. Three patients had no evidence of ovarian cancer. Three patients died of TRL at 4 days, 5 months, and 11 months, one patient remained in remission at 25 months after diagnosis of TRL. CONCLUSION: Patients receiving taxane/platinum therapy should undergo long-term follow-up with attention to the development of TRL, even if the gynecologic malignant cancer is in remission.

Mid-term functional recovery after tricuspid annuloplasty concomitant with left-sided valve surgery.

BACKGROUND: To elucidate the impact of tricuspid annuloplasty concomitant with left-sided valve surgery on the right ventricular (RV) function in patients with mild or more tricuspid regurgitation (TR). METHODS: We enrolled 136 patients with mild or more TR who underwent left-sided valve surgery. Seventy-three patients underwent left-sided valve surgery alone (group non-T) and 63 underwent concomitant tricuspid annuloplasty (group T). The echocardiographic data at the latest follow-up (mean 1019 days) were compared using multiple regression analysis to adjust cofounding factors. Propensity score was calculated and included in the analysis as a covariate. In addition, propensity score matching was used for sensitive analysis (12 pairs). RESULTS: In group non-T, there were more aortic valve surgeries, and fewer mitral valve surgeries. At baseline, body surface area, New York Heart Association class, and prevalence of atrial fibrillation were significantly different between groups. On preoperative echocardiography, left and right atrial diameter, RV diameter, and tricuspid annular diameter were larger in group T, whereas there was no significant difference in RV fractional area change. In multiple regression analyses, RV diameter in diastole was significantly lower and RV fractional area change was significantly higher at the follow-up period in group T. These results were not attenuated even in subgroup analysis in patients with only mild TR or mitral valve surgery alone. CONCLUSION: Among patients with mild or more TR, RV dimensional and functional recovery was not obtained with left-sided valve surgery alone. Adding tricuspid annuloplasty may potentially achieve both outcomes.

[Aortic Valve Translocation for Severe Prosthetic Valve Endocarditis with Aortic Annular Abscess].

We report a case of successful aortic valve translocation in a 71-year-old man with severe prosthetic valve endocarditis and an aortic annular abscess. Six years earlier, the patient had undergone aortic valve replacement for aortic regurgitation and coronary artery bypass grafting to the left anterior descending artery with a saphenous vein. Moreover, 4 years earlier, he had undergone total arch replacement for chronic aortic dissection. He was admitted to our hospital with suspected urinary tract infection. Despite antibiotic therapy, the patient developed a high fever. Transthoracic echocardiography revealed a rocking motion of the prosthetic aortic valve, and an emergency operation was performed. An annular abscess surrounding the prosthetic aortic valve was observed, and the valve was detached. For destruction of the entire aortic annulus, we performed an aortic valve translocation procedure. Revascularization of the left coronary artery was performed by interposing an 8 mm artificial graft between the proximal anastomosis site of the previous venous graft and the composite tube graft. Revascularization of the right coronary artery was performed using a saphenous vein graft. The patient was discharged uneventfully at postoperative day 29 and doing well 1 year after surgery.

The frozen elephant trunk technique for acute retrograde type A aortic dissection: preliminary results.

OBJECTIVES: Our goal was to determine the early and midterm outcomes after total arch replacement with the frozen elephant trunk (FET) technique compared to those of the conventional elephant trunk (ET) technique for acute retrograde type A aortic dissection. METHODS: Between 2012 and 2019, a total of 49 patients had total arch replacement for acute retrograde type A aortic dissection. Patients were divided into the conventional ET (n = 17) and FET (n = 32) groups. The false lumen status was evaluated using enhanced computed tomography (CT) 1 week postoperatively. The diameter of the downstream aorta was evaluated annually using CT. The median follow-up period was 29 months. RESULTS: Preoperative data and neurological complications were not significantly different in the 2 groups. The diameter and length of the ET prosthesis were significantly larger and longer in the FET group. The overall early mortality rate was 10.2% (5/49) with no differences between the 2 groups. The mean follow-up period was significantly longer in the conventional ET group. The rates of freedom from aortic events at 3 years were significantly lower in the FET group. At the level of the distal arch, postoperative false lumen patency was significantly lower and the follow-up aortic diameter was significantly smaller in the FET group. CONCLUSIONS: The FET technique facilitates false lumen thrombosis and aortic remodelling at the distal arch level, with fewer adverse aortic events during the follow-up period with acceptable early outcomes; however, these findings are exploratory and require investigation.

Lymphadenectomy for primary ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness of lymphadenectomy at primary debulking surgery (PDS) on the survival of patients with epithelial ovarian cancer (EOC). METHODS: We searched PubMed, Ichushi, and the Cochrane Library. Randomized controlled trials (RCTs) and retrospective cohort studies comparing survival of women with EOC undergoing lymphadenectomy at PDS with that of women without lymphadenectomy were included. We performed a meta-analysis of overall survival (OS), progression-free survival (PFS), and adverse events. RESULTS: For advanced-stage EOC, 2 RCTs including 1,074 women and 7 cohort studies comprising 3,161 women were evaluated. Meta-analysis revealed that lymphadenectomy was associated with improved OS (hazard ratio [HR]=0.80; 95% confidence interval [CI]=0.70-0.90). However, meta-analysis of 2 RCTs revealed no significant difference in OS between the lymphadenectomy and no-lymphadenectomy groups (OS: HR=1.02; 95% CI=0.85-1.22). For early-stage EOC, 1 RCT comprising 268 women and 4 cohort studies comprising 14,228 women were evaluated. Meta-analysis showed that lymphadenectomy was associated with improved OS (HR=0.75; 95% CI=0.68-0.82). A RCT of early-stage EOC reported that lymphadenectomy was not associated with improved OS (HR=0.85; 95% CI=0.49-1.47). Surgery-related deaths were similar in both groups (risk ratio [RR]=1.00; 95% CI=0.99-1.01); however, blood transfusion was required less frequently in the no-lymphadenectomy group (RR=0.74; 95% CI=0.63-0.86). CONCLUSIONS: Meta-analysis of RCTs and observational studies suggest that lymphadenectomy was associated with improved OS in advanced- and early-stage EOC. However, results from RCTs demonstrate that lymphadenectomy was not associated with improved OS in advanced- and early-stage EOC.

[Experiences of Cardioaortic Surgery with Small Anterior Mediastinal Mass on Preoperative Computed Tomography].

Computed tomography(CT) is indispensable for diagnostic imaging. During preoperative assessment for cardioaortic surgery, a CT examination is performed not only for diagnostic purposes but also to decide the surgical strategy. In some cases, CT demonstrates a small abnormal mass in the adipose tissue of the anterior mediastinum. Sometimes radiologists diagnose the image and send the diagnostic report to cardiologists or cardiovascular surgeons. However, they tend to limit their focus to their field of specialty. Thus, they might overlook or underestimate an abnormal mass. Anterior mediastinal masses, though small, may include malignant tumors. Thus, we reviewed 12 cases in which anterior mediastinal masses were found on preoperative CT. Two of these patients were finally diagnosed with malignant tumors. We should pay attention to not only cardiovascular assessment but also mediastinal masses on preoperative CT. In some cases, concomitant surgery for cardioaortic disease and an anterior mediastinal tumor is effective.

Impact of tricuspid annuloplasty on postoperative changes in the right ventricular systolic and diastolic function: A retrospective cohort study.

OBJECTIVES: To elucidate the impact of regulation of tricuspid regurgitation (TR) using tricuspid annuloplasty on postoperative changes in right ventricular (RV) systolic and diastolic functions. METHODS: We enrolled 69 patients who underwent aortic or mitral valve surgery between July 2016 to March 2018 without recurrence. Patients with concomitant coronary artery bypass grafting or a history of previous cardiovascular surgery were excluded, remaining 45 patients enrolled. Patients were divided into two groups according to concomitant tricuspid annuloplasty (T: n = 12 vs non-T: n = 33). RV global longitudinal strain (RVGLS), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), and early tricuspid inflow velocity/early diastolic tricuspid annular velocity ratio (tricuspid E/e') were assessed as functional indices at preoperative, postoperative and 1-year follow-up periods. RESULTS: RVFAC deteriorated postoperatively but recovered at follow-up in group T, whereas that in group non-T showed gradual deterioration overtime. RVGLS and TAPSE showed similar temporary deterioration and recovery between groups. Tricuspid E in group T increased postoperatively and showed significant difference, which was kept until follow-up period. Tricuspid e' decreased postoperatively, and recovered slightly in both groups. As a result, postoperative RV diastolic function (tricuspid E/e') showed significant difference between groups. This difference was maintained until follow-up. CONCLUSIONS: RV systolic function deteriorated postoperatively, but there was a tendency to improve at follow-up regardless of tricuspid annuloplasty. RV diastolic function may potentially be impaired when TR was regulated by tricuspid annuloplasty.

PD-L1 and CD4 are independent prognostic factors for overall survival in endometrial carcinomas.

BACKGROUND: Tumor microenvironment (TME) including the immune checkpoint system impacts prognosis in some types of malignancy. The aim of our study was to investigate the precise prognostic significance of the TME profile in endometrial carcinoma. METHODS: We performed immunohistochemistry of the TME proteins, PD-L1, PD-1, CD4, CD8, CD68, and VEGF in endometrial carcinomas from 221 patients. RESULTS: High PD-L1 in tumor cells (TCs) was associated with better OS (p = 0.004), whereas high PD-L1 in tumor-infiltrating immune cells (TICs) was associated with worse OS (p = 0.02). High PD-L1 in TICs correlated with high densities of CD8+ TICs and CD68+ TICs, as well as microsatellite instability (p = 0.00000064, 0.00078, and 0.0056), while high PD-L1 in TCs correlated with longer treatment-free interval (TFI) after primary chemotherapy in recurrent cases (p = 0.000043). High density of CD4+ TICs correlated with better OS and longer TFI (p = 0.0008 and 0.014). Univariate and multivariate analyses of prognostic factors revealed that high PD-L1 in TCs and high density of CD4+ TICs were significant and independent for favorable OS (p = 0.014 and 0.0025). CONCLUSION: The current findings indicate that PD-L1 and CD4+ helper T cells may be reasonable targets for improving survival through manipulating chemosensitivity, providing significant implications for combining immunotherapies into the therapeutic strategy for endometrial carcinoma.

Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma.

Type II endometrial carcinoma mainly originates from p53 aberration. However, the detailed prognostic significance of p53 aberration in endometrial carcinoma remains to be clarified. In the present study, abnormal p53 accumulation was analyzed using immunohistochemical techniques in endometrial carcinoma samples derived from 221 consecutive patients. The expression levels of p53 were associated with clinicopathological parameters and patient survival. P53 overexpression was observed in 37/221 patients (17%), and was associated with non-endometrioid histology, post-menopause and advanced tumor stage (III/IV; P=0.0006, P=0.03 and P=0.025, respectively). Survival analysis indicated that patients with p53-overexpressing tumors exhibited poor overall survival (OS) compared with patients without p53 overexpression (P<0.000001). Univariate and multivariate analyses demonstrated that the parameters p53 overexpression, age ≥70, non-endometrioid histology and advanced stage were significant and independent prognostic factors for poor OS (P=0.00012, P=0.00048, P=0.0027 and P=0.0015, respectively). Additionally, adjuvant radiotherapy was associated with increased OS in patients without p53 overexpression. This finding was not observed for patients with adjuvant chemotherapy. In contrast to patients without p53 overexpression, patients with p53 overexpression exhibited no association with OS (P=0.02 vs. P=0.40). Notably, adjuvant radiotherapy was identified to be a significant prognostic factor for favorable OS in the subset of patients that did not exhibit p53 overexpression and received post-operative treatment (P=0.026). The findings suggested that abnormal p53 accumulation may influence patient survival via unfavorable biological tumor properties, including rapid progression and radioresistance. The present study offered valuable insights for the genome-directed management of endometrial carcinoma.

Structural Dynamics of Lipid Bilayer Membranes Explored by Magnetic Field Effect Based Fluorescence Microscopy.

Lipid bilayer membranes are known to exist as heterogeneous and dynamic structures where the molecules are always moving and fluctuating under physiological conditions. Magnetic field effects (MFEs) studied herein are phenomena in which the exciplex emission from an electron donor-acceptor dyad increases or decreases by applying an external magnetic field. The characteristic dependence of MFEs on the viscosity and polarity of the surrounding medium has been applied to investigate the local environments around the probe molecule. In this study, a novel MFE-based fluorescence microscopy technique was developed to explore the structural dynamics of lipid bilayer membranes. The vesicle formation during the membrane deformation was selectively visualized through the MFEs, thus allowing the extraction of information on the cellular dynamics at high temporal and spatial resolutions. This highly versatile and powerful technique is applicable to a wide range of areas, such as biology and material science.

Predictors of favorable survival after secondary cytoreductive surgery for recurrent endometrial cancer.

OBJECTIVE: The selection criteria for secondary cytoreductive surgery (SCS) for recurrent endometrial cancer (EC) remain to be defined. The present study aimed to identify predictors for favorable survival after SCS for the disease. METHODS: We retrospectively reviewed the medical records of 112 patients who relapsed by 2016 among 1052 who were diagnosed with primary EC between 1985 and 2014. Characteristics associated with overall survival (OS) after SCS were identified using univariate and multivariate analyses. RESULTS: Twenty-nine of the 112 patients who relapsed underwent SCS. Complete resection was achieved in 18 (62%) patients, whose OS after SCS was significantly better than that of patients receiving incomplete resection (68 vs. 20 months; p = 0.001). Endometrioid histology and performance status (PS) 0 were significant and independent factors for a favorable OS (p = 0.005, and 0.049). The OS of patients with both factors was better than patients with one or no factors (median 75, 19 and 4 months; p = 0.001 and 0.00001). The number of predictors was associated with the rate of complete resection (p = 0.001). CONCLUSIONS: Patients with endometrioid histology and PS 0 should be offered SCS for recurrent EC. Prospective trials are warranted to verify this proposal.

Human papillomavirus genotype and prognosis of cervical cancer: Favorable survival of patients with HPV16-positive tumors.

The prognostic impact of human papillomavirus (HPV) type on invasive cervical cancer (ICC) was analyzed for 137 women treated for ICC at a single institution between 1999 and 2007. The study subjects were divided into three groups according to HPV genotype: HPV16-positive (n = 59), HPV18-positive (n = 33), and HPV16/18-negative ICC (non-HPV16/18, n = 45). The median follow-up time was 102.5 months (range, 5-179). The 10-year overall survival (10y-OS) rates in women with FIGO stage I/II disease were similar among HPV genotypes: 94.7% for HPV16 (n = 39), 95.2% for HPV18 (n = 26), and 96.4% for non-HPV16/18 (n = 29). However, the 10y-OS rates in women with FIGO stage III/IV tumors were 73.7% for HPV16 (n = 20), 45.7% for HPV18 (n = 7), and 35.7% for other types (n = 16), with significantly higher survival in HPV16-positive compared with HPV16-negative ICC (10y-OS; 73.7% vs. 39.5%, P = 0.04). This difference in FIGO stage III/IV tumors remained significant after adjusting for age and histology (hazard ratio 0.30, 95% confidence interval 0.09-0.86, P = 0.02). These results suggest that detection of HPV16 DNA may be associated with a favorable prognosis in patients with FIGO stage III/IV ICC. Given that most women with FIGO stage III/IV tumors received concurrent chemoradiotherapy, this finding may imply that HPV16-positive tumors are more chemoradiosensitive.

Off-pump resection of a giant inflamed epicardial cyst.

BACKGROUND: Epicardial cysts are rarer benign tumors than pericardial cysts. There have been few reports on surgical management for epicardial cysts. CASE PRESENTATION: A 73-year-old woman with dyspnea on exertion had a giant cyst (12 × 10 cm in diameter) on preoperative computed tomography. Compression of the left atrium and ventricle by the cyst was considered to be the cause of her symptoms. The cyst was diagnosed with an epicardial cyst intraoperatively. Although the cyst adhered to surrounding tissues, it was successfully resected with off-pump surgery by using a heart positioner and an ultrasonic scalpel. CONCLUSIONS: Surgeons should consider off-pump surgery as an alternative to video-assisted thoracoscopic surgery and on-pump surgery for complicated epicardial cysts.

Prognostic significance of PIK3CA mutation in stage IIB to IVA cervical cancers treated by concurrent chemoradiotherapy with weekly cisplatin.

The standard treatment for locally advanced cervical cancer is cisplatin-based concurrent chemoradiotherapy (CCRT). Although the activated PI3-kinase/Akt pathway is known to be involved in both cisplatin-resistance and radioresistance, to date, only a few studies have reported significant associations between PIK3CA gene mutational status and outcome by CCRT in the disease. The aim of this study was to clarify the prognostic significance of PIK3CA mutational status in cervical cancers treated by CCRT.We analyzed PIK3CA mutation in 59 patients with stage IIB to IVA cervical carcinomas primarily treated by CCRT with weekly cisplatin using formalin-fixed paraffin-embedded biopsy specimens before treatment. Fifty-seven of 59 patients (97%) had locally advanced cancers with stage IIIA to IVA. Clinicopathologic data and patient survival were retrospectively compared according to PIK3CA mutational status.PIK3CA mutation was found in 7 of 59 patients (12%). No significant differences in clinicopathologic characteristics were observed according to PIK3CA mutational status. Patients with wild-type PIK3CA showed significantly improved cancer-specific survival as compared with mutated patients (P = .044). Subsequent survival analyses revealed that PIK3CA mutation was a significant prognostic factor for poor overall survival [multivariate adjusted hazard ratio (HR), 3.9; 95% confidence interval (95% CI), 1.3-11.8; P = .017] and cancer-specific survival (multivariate adjusted HR, 3.6; 95% CI, 1.2-11.0; P = .024).Together with previous published findings, the current study further supports the clinical significance of PIK3CA mutation in cervical cancer. Our observations suggest that molecular inhibitors targeting the PI3-kinase/Akt pathway may improve the outcome by CCRT in cervical cancers harboring PIK3CA mutation, providing significant implications for novel treatment strategy based on precision medicine in the disease.

Effect of tricuspid annuloplasty concomitant with left heart surgery on right heart geometry and function.

OBJECTIVES: To elucidate the effect of tricuspid annuloplasty concomitant with left-sided valve surgery on the right heart in patients with mild or more tricuspid regurgitation (TR). METHODS: We enrolled 78 patients with mild or more TR who underwent left-sided valve surgery. Forty-three patients underwent only left-sided valve surgery (group non-T) and 35 underwent concomitant tricuspid annuloplasty (group T). Echocardiographic changes between the preoperative and 1-year follow-up periods were compared. Propensity score matching was used to obtain risk-adjusted outcome comparisons (16 pairs). RESULTS: In group non-T, there were more operations for aortic stenosis and concomitant coronary artery bypass grafting, and fewer operations for mitral regurgitation. The prevalence of atrial fibrillation was higher in group T. In preoperative echocardiography, there were no significant differences in left ventricular and right ventricular (RV) dimensions and functions. Tricuspid valve annular diameter and TR-related parameters were significantly larger in group T. Left ventricular dimensions and TR-related parameters significantly improved in both groups 1 year after operation. RV diameter was significantly reduced in only group T. In analysis of variance, RV diameter in systole and diastole showed significant interaction, whereas left heart dimensions and function, tricuspid valve tethering height, and RV fractional area change did not show interaction. These results were not attenuated even after propensity-matching analyses. CONCLUSIONS: Among patients with mild or more TR, RV reverse remodeling was not obtained with left-sided valve surgery alone. Additional use of tricuspid annuloplasty might potentially achieve favorable TR regulation as well as RV reverse remodeling.

Separate analysis of human papillomavirus E6 and E7 messenger RNAs to predict cervical neoplasia progression.

A few studies previously suggested that human papillomavirus (HPV) E6 messenger RNA (mRNA) may exist uniformly in all grades of cervical intraepithelial neoplasia (CIN), whereas the detection rate of E7 mRNA may increase with disease progression from low-grade CIN to invasive carcinoma. The aim of this study was to clarify the different roles of E6 and E7 mRNAs in cervical carcinogenesis. The presence of each E6 and E7 mRNA was analyzed in 171 patients with pathologically-diagnosed CIN or cervical carcinoma. We utilized a RT-PCR assay based on consensus primers which could detect E6 mRNA (full-length E6/E7 transcript) and E7 mRNAs (spliced E6*/E7 transcripts) separately for various HPV types. E7 mRNAs were detected in 6% of CIN1, 12% of CIN2, 24% of CIN3, and 54% of cervical carcinoma. The presence of E7 mRNAs was significantly associated with progression from low-grade CIN to invasive carcinoma in contrast with E6 mRNA or high-risk HPV (HR-HPV) DNA (p = 0.00011, 0.80 and 0.54). The presence of both E6 and E7 mRNAs was significantly associated with HPV16/18 DNA but not with HR-HPV DNA (p = 0.0079 and 0.21), while the presence of E6 mRNA was significantly associated with HR-HPV DNA but not with HPV16/18 DNA (p = 0.036 and 0.089). The presence of both E6 and E7 mRNAs showed high specificity and low sensitivity (100% and 19%) for detecting CIN2+ by contrast with the positivity for HR-HPV DNA showing low specificity and high sensitivity (19% and 89%). The positive predictive value for detecting CIN2+ was even higher by the presence of both E6 and E7 mRNAs than by the positivity for HR-HPV DNA (100% vs. 91%). In 31 patients followed up for CIN1-2, the presence of both E6 and E7 mRNAs showed significant association with the occurrence of upgraded abnormal cytology in contrast with E6 mRNA, HR-HPV DNA, or HPV16/18 DNA (p = 0.034, 0.73, 0.53, and 0.72). Our findings support previous studies according to which E7 mRNA is more closely involved in cervical carcinogenesis than E6 mRNA. Moreover, the separate analysis of E6 and E7 mRNAs may be more useful than HR-HPV DNA test for detecting CIN2+ precisely and predicting disease progression. Further accumulation of evidence is warranted to validate our findings.