Maria Teresa Bruno

Role of endocervical curettage in detecting CIN2 + in postmenopausal women with persistent high-risk HPV and type 3 transformation zone

This study aimed to evaluate the effectiveness of endocervical curettage (ECC) in detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HPV-positive postmenopausal women with a type 3 transformation zone (TZ3) and to identify additional predictive factors. A retrospective observational study was conducted including 137 HPV-positive postmenopausal women who underwent colposcopy, ECC, and subsequent LEEP. Variables analyzed included age group, HPV genotype (16/18 vs. non-16/18), transformation zone type, cytology results, and ECC findings. Univariate and multivariable logistic regression analyses were performed to identify predictors of CIN2 + confirmed by LEEP histology. CIN2 + prevalence was 27.7% (38/137); ≥CIN3 occurred in 26/137 (19.0%). In multivariable analysis, high-grade cytology (adjusted OR [aOR] 4.65; 95% CI 1.92-11.30; p < 0.001), TZ3 (aOR 3.05; 1.05-8.85; p = 0.040) and hrHPV non-16/18 (aOR 2.52; 1.08-5.90; p = 0.032) were independently associated with CIN2+, while age ≥ 51 years was not (aOR 1.28; 0.57-2.85; p = 0.55). Absolute risks of CIN2 + were 36.8% with non-16/18 vs. 16.4% with HPV16/18. ECC (cut-off CIN2+) yielded sensitivity 73.7%, specificity 77.8%, PPV 56.0% and NPV 88.5%. In postmenopausal women with persistent hrHPV, high-grade cytology and TZ3 are the main drivers of CIN2+ risk. ECC is most useful as a rule-out test (high NPV), whereas expedited diagnostic-therapeutic LEEP may be considered when ASC-H/HSIL coexists with TZ3 in women without fertility desire. The association between non-16/18 genotypes and CIN2+ observed here warrants confirmation in larger multicentre cohorts.

Conservative management of CIN2 p16 positive lesions in women with multiple HPV infection

Abstract Background According to the 2006 American Society for Colposcopy and Cervical Pathology guidelines, positive CIN2 p16 in women over the age of 25 should be managed with excisional treatment. However, excisional treatment is associated with physical, psychological and obstetric morbidity and can have a negative impact on sexual function. In our study we sought to identify a clear management strategy, addressing the impact of routine use of p16 immunohistochemistry in this population and identify appropriate criteria for patient selection with the aim of reducing over-treatment. Method We studied the medical records of 130 patients who had undergone laser therapy for CIN2. Each patient underwent colposcopy, biopsy and HPV test and were tested for p16 protein,. Patients were divided based on HPV infection into: single infections, multiple infections. All patients underwent ZTA laser therapy with follow-up (2-year follow-up). Statistical analysis Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p  &lt; 0.05 were considered statistically significant. Results Single infections had a histological regression of 61.8% (21/34) and a histological persistence rate of 35.3% (12/34), which was greater than the multiple infection rate. The common characteristic that the women with persistence and progression had was the dimension of the lesion and the genotype 16. Ten cases of histological persistence and the only case of progression had one lesion greater than three quarters of the cervix. Conclusions With the progress of our understanding of the natural history of infection from human papillomavirus and the increasing use of colposcopy, thanks to the addition of HPV genotyping and the technique of immunohistochemistry, conservative management of these lesions is now possible.

Multiple HPV 16 infection with two strains: a possible marker of neoplastic progression

Abstract Background We studied the cases of single and multiple HPV infection and analyzed the correlation with negative cases, and preneoplastic and neoplastic lesions of the uterine cervix with the aim of making a contribution to the prognostic factor under discussion. Methods Nine hundred nine women undergoing second level screening because they had been positive at cervical cytology were enrolled. All the patients underwent colposcopy and cervical biopsy with viral genotyping. We divided mHPV infection based on the number of genotypes present: infections with 2 strains, 3 strains, 4 strains and 5 or more strains. Statistical analysis The analysis of the data was made using the χ2 test. Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p  &lt; 0.05 were considered statistically significant. Results The presence of genotype HPV16 in our study was associated with a 12 times greater risk of developing a high-grade lesion, OR = 12.70. The patients with single infections had the highest incidence of CIN2+ (34.1%) with respect to those with multiple infections (10.6%).When we studied in the mHPV infection the prevalence of the combinations between the genotypes, we found that in mHPV16 infections, the combinations HPV16, 18 and HPV16, 31 were the most frequent (55.5%) in CIN3 lesion. Conclusions Our results suggest that single HPV infections have a greater risk of developing SCC with respect to multiple infections. Multiple HPV infections are relevant only in the first phase of the lesion (CIN1-CIN2), while they are absent in carcinomas, where infections are of a single genotype. In particular, among multiple infections, HPV16 infection with 2 HR genotypes is associated significantly with CIN2 / CIN3 (21/30) and has 4 times greater risk of developing a high-grade lesion. Thus, it is probable that only specific combinations of HPV (HPV16,18 - HPV 16,31) can be associated with a clinically significant impact, while other combinations can simply be correlated because of a common infection or diagnostic method used. Therefore, multiple HPV16 infections with two high-risk genotypes is a major risk of CIN2/CIN3.

Spontaneous regression of cervical intraepithelial neoplasia 3 in women with a biopsy—cone interval of greater than 11 weeks

AbstractBackgroundAlthough there is broad consensus that only a subset of CIN3 will progress to cancer, there is currently no surefire way to predict which CIN3 will regress. Understanding the natural history of CIN3 is important, and finding markers for progression or regression could improve treatment strategies. According to the guidelines of the American Society for Colposcopy and Cervical Pathology of 2006, positive CIN3 p16 in women should be managed with excisional treatment (LEEP). For ethical reasons we cannot fail to treat women with CIN3 in order to study their regression capacity so we conducted a retrospective study to evaluate the regression rate of CIN3 diagnosed with a biopsy by studying the histological result of the cone removed by LEEP. We also investigated age, HPV genotypes and biopsy-cone interval distance as possible regression factors.MethodsWe selected 171 women with a histological diagnosis of positive CIN3 p16 as an entry criterion. All patients underwent LEEP / biopsy. A histological diagnosis of the cone of CIN3 or higher was considered as persistence or progression, the diagnosis of CIN1 or lower was considered as regression of the lesion.We used out a logistic model to study the probability of spontaneous regression of CIN3 as a function of the patient’s age, the time elapsed between the biopsy and the cone (in weeks) and the HPV genotype.ResultsWe found that the spontaneous regression rate of CIN3 was 15,8%, which was strongly associated with the biopsy-cone interval &gt; 11 weeks. Genotype 16, the most represented, was present both in cases of regression (77.8%) and in persistence (83.3%). Regarding age, the estimated odds ratio of the probability of observing a regression in women over 25 years of age was 0.0045 times that of women under 25 years of age (CI: 0.00020, 0.036). Neither age nor viral genotype are significant as predictors of regression.ConclusionTo wait at least 11 weeks from the biopsy before subjecting the woman to LEEP could prevent unnecessary LEEP procedures, considering also that from CIN3 to carcinoma it takes years before the neoplastic transformation takes place.

Possible role of negative human papillomavirus E6/E7 mRNA as a predictor of regression of cervical intraepithelial neoplasia 2 lesions in hr-HPV positive women

Abstract Background The aim of this study was to evaluate the regression rate of CIN2 p16 positive lesions in women over 25 years of age and identify possible predictors of regression. Methods A total of 128 CIN2 p16 positive patients over 25 years old were considered. The women met the following inclusion criteria: HPV genotype 16, 18, 31, 33, 45 positive, HPV E6 / E7 mRNA test positive, without immune system pathologies, not pregnant and had completed at least two years of follow-up. At each follow-up examination patients were examined by colposcopy, HPV test, E6/E7mRNA, targeted biopsy and p16 protein detection. The final state after the two years of follow-up was classified as progression if the histology showed a CIN3, persistence if the lesion was a CIN2, regression if negative or LSIL. The predicted regression factors evaluated were: HPV E6/E7mRNA, protein p16. Results Overall, we had 35.1% (45 cases) of progression to CIN3, 41.4% (53 cases) of persistence and 23.4% (30 cases) of regression. The regression rate was higher in women with negative mRNA 92.8% (26/28), OR 312 (34.12–1798.76) p = 0.0001, while women with p16 negative had a regression of 22.6% (7/31), OR 0.94 (95% CI 0.36–2.46), p was not significant. We found no significant difference in regression between p16 positive (23.7%) and p16 negative (22.6%) CIN2 p16 lesions. p16 had a VPN of 22.6 (CI 95% 0.159–0.310), indicating that a p16 negative lesion does not exclude a CIN2 + . Conclusions We had a regression rate of 23.4%, which was low if we consider that in the literature the regression rates vary from 55 to 63%. The discrepancy in the results may indeed be explained by the fact that all lesions in our study were hr-HPV positive and belonged to “older women” reflecting a more "high-risk" population. As regression factors we studied p16 and HPV E6/E7 mRNA. The results of our study show that HPV mRNA, if negative, appears to be able to identify CIN2 lesions with a higher probability of regression and underlines how a p16 negative is not an indicator of regression.