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The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy.Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models.Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945.The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

Objective The goal of this study was to determine the clinical factors independently associated with inaccuracy of colposcopically directed punch biopsy in defining extent and severity of epithelial lesions of the cervix. Methods The study was conducted in a colposcopy clinic devoted to the management of patients with abnormal Pap smear and/or histology diagnosis of cervical intraepithelial neoplasia (CIN) on punch biopsy or endocervical curettage. Seven hundred and thirty-nine patients (median age, 33 years; range, 18–83 years) referred with a punch biopsy diagnosis of CIN2–3 and treated with electrosurgical conization were evaluated. Cone histology diagnosis was assumed to supply the correct diagnosis. Two types of deviation of biopsy diagnosis were considered: (1) unconfirmed high-grade CIN diagnosis, defined as a cone diagnosis of CIN1 and reactive/reparative changes, and (2) nondiagnosis of carcinoma, defined as a cone diagnosis of microinvasive and invasive squamous carcinoma. Multinomial logistic regression analysis was used to assess the determinants of the probability of each type of deviation. Results The probability of unconfirmed high-grade CIN diagnosis ( n = 190, 25.7%) was inversely related to number of quadrants involved, severity of referral Pap smear, and grade of biopsy. The probability of nondiagnosis of carcinoma ( n = 43, 5.8%) was positively related to patient age, invisibility of the squamocolumnar junction, number of quadrants involved, and cone width. Endo-ectocervical location, cone depth, and time period had no effect whatsoever. Conclusions The study confirmed previous observations regarding the positive association of patient age and invisibility of squamocolumnar junction with the probability of nondiagnosis of carcinoma. The concomitant positive effects of number of quadrants involved and cone width were suggested to mirror the effect of circumferential development and, respectively, surface area of CIN. Severity of referral Pap smear and grade of biopsy were shown to be inversely related to the probability of a cone diagnosis of CIN1 and benign changes.

Objective. Cone margin status has been reported to be the most important predictor of residual disease in patients with cervical intraepithelial neoplasia (CIN) undergoing electrosurgical excisional treatment. The primary aim of this study of patients treated with electrosurgical conization was to evaluate the association of cone margin status and other clinical and pathologic factors with the probability of residual disease. Methods. The study population comprised 699 patients with at least one follow-up visit within 12 months of conization. Residual disease was defined as a histology diagnosis of CIN within 3 years of conization. Multivariate associations were evaluated with multiple logistic regression analysis. Results. Attendance to follow-up was 97% for the second visit and 34% for the third visit. Residual disease was detected in a total of 38 patients (5.4%). The detection rate was 3.3% at the first visit, 2.1% at the second visit, and 0.4% at the third visit. An increased probability of residual disease was associated with a referral Pap smear reported as high-grade squamous intraepithelial neoplasia and carcinoma (odds ratio, 2.9; reference category, low-grade squamous intraepithelial neoplasia). A decreased probability was associated with a squamocolumnar junction entirely visible at the first follow-up visit (odds ratio, 0.2; reference category, squamocolumnar junction not visible). Patient age, time period, lesion size, lesion site, grade of CIN, cone width, cone depth, and margin status had no influence. Conclusions. The determinants of residual disease in this study differed from those generally reported so far. Factors associated with effectiveness of electrosurgical treatment of CIN need further research.

Cervicography and HPV DNA testing have been proposed as intermediate triage techniques for the management of patients with Pap smear showing minor-grade atypia. The aims of the present study of 221 patients with positive Pap smear (ages 16-65) were (1) to evaluate the association of cervicography and HPV DNA test with the probability of biopsy and final histology diagnosis of CIN2 or worse, (2) to identify the combinations of results on cervicography and HPV DNA test associated with the absence of such lesions, and (3) to estimate the cost of a potential triage protocol for patients with HPV-CIN1 smear. The probability of biopsy showed a univariate association with the severity of the smear result and the cervicography classification but not the HPV DNA test. In the multivariate analysis, only the cervicography result was a significant predictor of biopsy. The final histology diagnosis showed a univariate association with each of the three tests and a multivariate association with the degree of cytology positivity and the cervicography result. Among patients with HPV-CIN1 smears, only a negative cervicography (with any HPV DNA test result) was always associated with the absence of severe histologic lesions. This pattern accounted only for 7% of such patients. The additional costs of a potential triage protocol based on cervicography were estimated to exceed the savings resulting from the reduced colposcopy rate.

In an external quality assurance (EQA) scheme, 110 selected cervical smears were independently reported by seven cytology laboratories using the 1988 Bethesda System. In one of these, a random sample of 60 study smears was independently classified by five cytologists before undergoing joint examination according to EQA protocol. Internal agreement (i.e., among these cytologists) was compared with external agreement (between these cytologists and the other six laboratories) and with interlaboratory agreement (among these laboratories). The kappa value for internal agreement on sample adequacy (0.57) was considerably greater than those for external (0.16) and interlaboratory agreement (0.10). For interpretation of epithelial abnormalities, internal kappa was excellent (0.80) but not substantially greater compared with external kappa (0.66) and interlaboratory kappa (0.70). Calculation of class-specific kappa values revealed (a) that superiority of internal agreement on sample adequacy was restricted to the notations of "less than optimal" and of "satisfactory," and (b) that internal increase in agreement on cytologic abnormalities was substantial for the diagnosis of "atypical cells of undetermined significance."