Cervical Intraepithelial Neoplasia Grade 3 (CIN3) in Women Younger than 30 Years Was Significantly Associated with HPV16/18 Genotypes.

BACKGROUND: The objective of the present study is to investigate the age-specific distribution of HPV genotypes in CIN3 lesions in screened unvaccinated women. These data are essential to optimize current and future screening programs. METHODS: A multicenter retrospective study was conducted. A total of 408 unvaccinated women with positive histology and a high-risk HPV genotype were enrolled. Each woman at baseline had HPV DNA testing and HPV genotyping, and all women underwent targeted biopsy and/or treatment with a loop electrosurgical excision procedure (LEEP) before entering the study. We divided the genotypes into HPV16/18 and HPV non-16/18 (HPV31/33/45/35/39/51/52/58/59/66/68). Women were divided into increasing age categories: <30, 30-44, and ≥45. RESULTS: The percentage of CIN3 associated with HPV16/18 is maximum in women under 30 years of age (85.1%), drops to 75.6% in women aged between 30 and 44 years, and up to 47.2% in women over 45 years. CIN3 in women younger than 30 years was significantly associated with HPV16/18 genotypes (p = 0). DISCUSSION: The data from the present study suggest that the risk of CIN3 is related to the woman's age and hr HPV genotype. The data highlight two different types of CIN3: a more frequent type, related to HPV16/18, which develops rapidly and in young women, and another, relating to non-16/18 HPV, which develops later at an advanced age and slowly, through low-grade lesions.

Extended Genotyping to Stratify the Risk of CIN2+ in Women with Persistent HPV Infection, Negative Cytology and Type 3 Transformation Zone.

Persistent human papillomavirus (HPV) infection is recognized as a major risk factor for cervical cancer. Women with persistent HPV and negative cytology are at greater risk of CIN2+ than women with negative infection. The diagnosis becomes more complicated when the woman has a type 3 transformation zone at colposcopy. The aim of this study was to determine the prevalence of CIN2+ in women with persistent HPV, negative cytology and TZ3; how to stratify the risk of CIN2+; and what the best diagnostic strategy is, given TZ3. METHODS: In a multicenter retrospective cohort study, we enrolled women with negative cytology and TZ3 among the 213 women referred for colposcopy for persistent HPV. The average age of the women was 53 years; in particular, 83% were postmenopausal women. In the presence of a TZ3, the entire transformation zone cannot be explored, making colposcopy and targeted biopsy useless and inadequate, with great risks of underdiagnosis or missed diagnosis. Women with TZ3 underwent diagnostic LEEP to ensure correct diagnoses. RESULTS: The study highlighted 19% (16/84) of CIN2+ lesions, a higher frequency of non-HPV 16/18 genotypes (76.2%), and 50% of CIN2+ lesions being due to non-HPV 16/18 genotypes. Furthermore, more than half of the women (80.9%) had normal histopathological results in the LEEP sample. CONCLUSION: Women with viral persistence, negative cytology, and TZ3 have a 19% risk of CIN2+; genotyping helps stratify risk, but extensive genotyping is necessary instead of partial genotyping (16/18), referring to a population of women over 50 years old in which the prevalence of genotypes 16,18 decreases and the prevalence of other genotypes increases; diagnostic LEEP is excessive (only 16 cases of CIN2+ out of 48 cases treated), even though 83% of women had viral clearance after LEEP; p16/Ki67 double staining could be a potential risk marker, which would only highlight women at risk of CIN2+ to undergo LEEP. To individualize the diagnostic workup and treatment and minimize the risk of under diagnosis and overtreatment, future studies should explore the use of extended genotyping and new biomarkers for individual risk stratification.

Stage II endometrial cancer: The diagnostic power of hysteroscopic excisional biopsy and MRI in the pre-operative cervical stroma assessment.

INTRODUCTION/BACKGROUND: Stage II Endometrial cancer (EC) accounts only for 12% of cases. Recent evidences redraw the weight of radicality in this stage as it would seem to have no impact on survival outcomes claiming for radicality when free surgical margins are not ensured to be achieved by simple hysterectomy. Thus, an accurate pre-operative evaluation might be crucial. This study aims to estimate the diagnostic power of Hysteroscopic excisional biopsy (HEB) of cervical stroma alone and combined with Magnetic resonance imaging (MRI) to predict the stage and concealed parametrial invasion in patients with preoperative stage II EC. METHODOLOGY: From January 2019 to November 2023, all patients evaluated at the Department of Gynaecology Oncology of Humanitas, Istituto Clinico Catanese, Catania, Italy, with a diagnosis of EC and evidence of cervical stromal diffusion on preoperative MRI and/or office hysteroscopy evaluation, considered suitable for laparoscopic modified type B hysterectomy, were consecutively included in the study. These underwent endometrial and cervical hysteroscopy excisional biopsy (HEB) for histological evaluation before definitive surgery. The data obtained were compared with the definitive histological examination (reference standard). RESULTS: Sixteen patients met the including/excluding criteria and were considered into the study. Stage II endometrial cancer were confirmed in 3 cases (18.7%). We reported 2 (12,5%) parametrial involvement (IIIB), 4 (25%) cases of lymph nodes metastasis (IIIc), 7 (43,7%) cases of I stage. MRI had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy (95% CIs) of 71%, 44%, 50%, 66% and 56.2 % respectively. HEB showed sensitivity, specificity, PPV, NPV and accuracy (95 % CI) of 85 %, 89 %, 85 %, 88 % and 87 % respectively. Comparing HEB + MRI to HEB alone, no statistical differences were noted in all fields. Considering parametrial invasion, MRI had better sensitivity but there were no statistical differences to HEB in other fields, showing both a worthy NPV. CONCLUSION: HEB was accurate in all fields for cervical stroma assessment and had a fine NPV to exclude massive cervical involvement up to parametrial. Considering the new FIGO staging a preoperative molecular and histological evaluation of the cervical stroma may be useful. Operative hysteroscopy seems to be a feasible and accurate method for this purpose.

The Impact of Diagnosis of Human Papillomavirus (HPV) Infection and Electrosurgical Excision Procedure (LEEP) for Cervical Intraepithelial Neoplasia 3 (CIN3) on Women's Sexual Lives.

The aim of the study was to assess sexual health in women who underwent Loop Electrosurgical Excisional Procedure (LEEP) for the treatment of cervical intraepithelial neoplasia 3 (CIN 3). One hundred thirty-one women were enrolled, and the Female Sexual Function Index (FSFI) questionnaire was administered before LEEP and 6 months after the procedure. In almost all of the participants, data revealed a statistically significant worsening in sexual quality of life after LEEP. Therefore, clinicians should be aware of these possible negative effects on sexual behavior, and provide women with appropriate, wide-ranging, and detailed counseling. The data obtained in the present study should help to plan appropriate counseling from communicating HPV diagnosis and medical treatment to CIN3 surgical procedure.

Oral and periodontal manifestation related during human papilloma virus infections: Update on early prognostic factors.

Human Papilloma Virus (HPV) is considered one of the most common sexually transmitted infections and has been shown to play an important role in the pathogenesis of squamous cell carcinomas (SCC) of the cervix and head and neck. Manifestations of HPV infections can be manifold, ranging from asymptomatic infections to benign or potentially malignant lesions to intraepithelial neoplasms and invasive carcinomas. The heterogeneity of clinical manifestations from HPV infection depends on the interactions between the viral agent and the host, a direct consequence of the ability on the part of HPV is to remain silent and to evade and convey the action of the host immune system. The oral mucosa represents one of the tissues for which HPV has a distinct tropism and is frequently affected by infection. While much information is available on the role that HPV infection plays in the development of SCC in the oral cavity, there is less information on asymptomatic infections and benign HPV-induced oral lesions. Therefore, the purpose of this review is to analyze, in light of current knowledge, the early clinical and bio-humoral prognostic features related to the risk of HPV malignant transformation, focusing on subclinical conditions, benign lesions, and the correlation between oral infection and infection in other districts. The data show that the main risk associated with HPV infection is related to malignant transformation of lesions. Although HPV-driven OPSCC is associated with a better prognosis than non-HPV-driven OPSCC, primary prevention and early detection of the infection and affected genotype are essential to reduce the risk of malignant neoplastic complications and improve the prognosis.

Correlation of the HPV 16 Genotype Persistence in Women Undergoing LEEP for CIN3 with the Risk of CIN2+ Relapses in the First 18 Months of Follow-Up: A Multicenter Retrospective Study.

OBJECTIVE: Specific hr-HPV genotypes have different natural histories and different oncogenic capacity. This study aimed to investigate the risk of CIN2+ recurrence of the individual genotypes and evaluate how the duration of HPV persistence influences the risk of developing recurrent 16 cervical dysplasia of high grade (CIN2+). METHODS: Data from patients with persistent HPV infection after primary conization were retrospectively extracted. Kaplan-Meier proportional hazards models were used to evaluate associations between the duration of HPV persistence and the risk of developing recurrent CIN2+. Kruskal-Wallis testing with Dunn's multiple comparison test was used to test whether there was a statistically significant difference in the time to development of tumor recurrences between different genotypes. RESULTS: Overall, 333 patients met the inclusion criteria. In 285 cases the HPV infection was persistent, in 48 cases (18%) it was transient, i.e., different genotypes after LEEP. Overall were diagnosed 39 relapses (13.7%), 79.5% (31/39 cases) were due to genotype 16, 20.5% (8/39) were linked to the other genotypes. Persistence of genotype 16 showed a 7-fold increased risk of developing a CIN2+ relapse, OR = 7.08 (95%CI: 3.12-16.08). Furthermore, the majority of relapses (38/39) occurred within 24 months of persistence with a cut-off represented by 18 months (p = 0.001) in which the relapse rate is maximum and the most frequently found genotype was the 16th with 31 (79.5%) cases of recurrence. Kruskal-Wallis test with Dunn's multiple comparisons has shown statistically significant difference in the time of development of CIN2 relapses among HPV16 and other genotypes. (p < 0.05). Kaplan-meier analysis has shown statistically significant difference between the time to CIN2+ relapse onset in patients with HPV 16 infection and patients with other hrHPV genotypes. (p < 0.05) Conclusions: the study results suggest that persistent HPV infection after LEEP with the same HR genotype present before surgery represents one of the most important predictive factors of the risk of CIN2+ recurrence. The persistence of HPV16 for the first 18 months strongly correlates with the risk of developing a CIN2+ recurrence.

The Coexistence of Cervical Intraepithelial Neoplasia (CIN3) and Adenocarcinoma In Situ (AIS) in LEEP Excisions Performed for CIN3.

The purpose of this study was to evaluate the incidence of AIS and AC in the histological cone of women treated for CIN3. Furthermore, through the study of the specific HR HPV genotypes, we obtained more information on the possible different nature between the single CIN3 lesion and the CIN3 coexisting with the glandular lesion. METHODS: A sample of 414 women underwent LEEP for CIN3. The study sample consisted of 370 women with a CIN3 lesion alone and 44 women with a CIN3 lesion coexisting with AIS or adenocarcinoma. We studied the individual HR HPV genotypes and their frequency in the two groups under study. Furthermore, the therapeutic results and follow-ups for the population were studied on the entire study sample. RESULTS: In patients with a single CIN3 lesion, 11 high-risk genotypes were detected; in patients with CIN3 associated with AIS or AC, only 4 different genotypes were detected (16, 18, 45, 33). Overall, the frequency of HPV 18 was significantly higher in CIN3 coexisting with AIS compared to solitary CIN3 lesions, χ2 = 27.73 (p < 0.001), while the frequency of other high-risk genotypes was significantly higher in patients with a single CIN3 than in patients with CIN3 coexisting with AIS. In our study population, mixed lesions (CIN3 coexisting with AIS), unlike their squamous counterparts (single CIN3 lesions), were characterized by skip lesions, which demonstrate more aggressive behavior and a higher rate of viral persistence and recurrence. CONCLUSION: A relatively high rate (10.7%) of AIS-AC was found in women treated for CIN3. Our study confirms the multifocal biological nature of the CIN3 lesion coexisting with AIS compared to the single CIN3 lesion. All this justifies the different treatments to which CIN3 lesions coexisting with AIS are addressed; in fact, the latter are treated with hysterectomy, while CIN3 is treated with conization alone.

Overexpression of E6/E7 mRNA HPV Is a Prognostic Biomarker for Residual Disease Progression in Women Undergoing LEEP for Cervical Intraepithelial Neoplasia 3.

The risk of overtreatment or not treating an occult carcinoma exists in women at risk of residual disease after a LEEP excision for CIN3. Our goal was to discover an efficient method to select patients requiring a second LEEP from those requiring a FU only through an mRNA-detection test. In a population of 686 women undergoing a LEEP excision for CIN 3, we selected 285 women at risk of residual disease and subjected them to a search for E6/E7 mRNA HPV. The women with negative mRNA were subjected to a follow up, while the women with positive mRNA were subjected to a second LEEP. The histological examination of the second cone revealed 120 (85.7%) cases of residual disease in the mRNA-positive women: 40 cases of CIN2, 51 cases of CIN3, 11 cases of squamous microinvasive carcinoma, 7 cases of squamous carcinoma, 9 cases of AIS (adenocarcinoma in situ) and 2 cases of adenocarcinoma. Among the mRNA-negative women undergoing a follow up, there were only five cases of residual disease. During the follow-up period of about 6 years, we witnessed the regression of the residual disease and the elimination of the virus, just as predicted by the negative result of the mRNA test. Testing patients for E6/E7 mRNA allowed us to identify women with residual disease (CIN2+) and treat them appropriately.

Oral HPV Infection in Women with HPV-Positive Cervix Is Closely Related to Oral Sex.

The oral transmission of HPV and, consequently, the risk of oral cancer has increased in the last years. Oral sex has often been implicated among the risk factors for oral HPV infections, however, there is still no consensus on these topics, nor on the relationship between genital and oral HPV infections. The present study aimed to evaluate the coexistence of papilloma virus, at the levels of the oral and genital mucosa, in women with a histologically confirmed HPV lesions (and a positive HPV test) at the genital level and a negative HPV control group. We also evaluated how some risk factors, such as smoking, the number of partners, age, and sexual habits can influence the possible presence of the virus itself in the oropharynx of the same women. In total, 117 unvaccinated women aged between 18 and 52 were enrolled. We found that the prevalence of oral HPV infection was high among the women with concomitant genital HPV infection (22%) compared to the HPV-negative women (0%), and the estimated odds ratio was 17.36 (95% CI: 1.02, 297.04). In none of the women with oral HPV did we find any relevant clinical lesions. The potential risk factors for HPV infections in the oropharynx and genitals were analyzed based on questionnaire responses. A multivariate analysis showed that genital HPV infections were significantly associated with a number of sexual partners > 10 (OR 138.60, 95% CI: 6.04-3181.30, p < 0.001), but the data also referred to having between 3-5 or 6-10 partners as being significant, as were a high level of education (OR 6.24, 95% CI: 1.67-4.23.26 p = 0.003), a frequency of sexual intercourse >10 (OR 91.67 95% CI: 3.20-2623.52, p = 0.004), oral sex (OR 6.16, 95% CI: 1.22-31.19, p = 0.014), and >20 cigarettes/day (OR 6.09 95% CI: 1.21-30.61, p = 0.014). Furthermore, being "separate" and having multiple sexually transmitted diseases were also significantly associated with genital HPV infection. In contrast, oral HPV infections were significantly associated with women aged 36 to 50 years (OR 27.38, 95% CI: 4.37-171.37; p = 0.000202) and oral sex (OR 95.5, 95% CI: 5.13-1782.75, p = 0.001126).Additionally, being separate, being cohabitant, lifetime sexual partners of >10, 3-5 lifetime sexual partners, <20 years of age, >10 sexual intercourse per month, occasional and regular anal sex, >20 cigarettes per day, a history of sexually transmitted disease (herpes and multiple), and having a history of genital warts were significant. Screening and early diagnosis are considered to be practically unfeasible for this category of cancer, given the lack of visible lesions; the 9-valent HPV vaccine remains the only means that could help to successfully counter the growing incidence of oral squamous cell carcinoma.

Performance of p16/Ki67 Immunostaining for Triage of Elderly Women with Atypical Squamous Cells of Undetermined Significance.

BACKGROUND: The p16/Ki67 technique has been poorly studied in postmenopausal women with ASC-US cytology. The objective of this study was to compare the accuracy of p16/Ki67 staining, HPV testing and HPV 16 genotyping for the identification of CIN2 + lesions in postmenopausal women with ASC-US cytology. METHOD: A total of 324 postmenopausal women with positive ASC-US were included. The women underwent HPV test, colposcopy, and biopsy. The slides were discolored and then stained with the CINtec Plus Kit for p16/Ki67. The HPV test results were classified as HPV16 +, hrHPV+ (other hrHPV genotypes), or HPV negative. RESULTS: The p16/Ki67 sensitivity for CIN2+ was 94.5%, the specificity 86.6%, PPV of 59% and NPV of 95.9%. The HPV test showed a sensitivity of 96.4% for CIN2+, a specificity of 62.8%, a PPV of 35% and a NPV of 98.8%. In postmenopausal women, the prevalence of genotype 16 decreases in favor of the other high-risk genotypes. CONCLUSION: Given the low sensitivity of cytology and the low percentage of HPV16-positive cancers among elderly women, triage via cytology and genotyping is not the best strategy; double staining cytology shows high profiles of sensibility and specificity for CIN2+ in ASCUS postmenopausal women.

Papillomavirus Infection as Potential Cause of Miscarriage in the Early Gestational Age: A Prospective Study.

The possible association between human papillomavirus (HPV) infection and negative pregnancy outcomes has been debated in the literature, with conflicting results from clinical trials. While some authors support a link between HPV and miscarriage, others argue that the mere detection of the virus does not necessarily indicate a causal relationship with negative pregnancy outcomes. In this study, we conducted a prospective, controlled investigation of the potential association between HPV infection and miscarriage. Our study included 59 women who had experienced a miscarriage and 57 women who had undergone voluntary termination of pregnancy (TOP) within the 12th week of gestation. We assessed HPV prevalence, maternal age, and HPV genotype in both groups and evaluated the relationship between these factors and pregnancy outcome. Unlike previous studies that only identified HPV in cases of abortion, we also correlated the positivity of chorionic villi with gestational age in both groups. We found a close correlation between positive chorionic villi and very early gestational age, with all 13 cases of virus-positive chorionic villi in the miscarriage group occurring in gestational periods of less than 8 + 5 weeks (<60 days) (RR = 28.6). Our analysis showed no correlation between HPV infection and maternal age or viral genotypes. The results suggest that the presence of HPV alone is not enough to cause spontaneous abortion, but a high viral load in early pregnancy may increase the risk of negative outcomes. These findings have important implications for the management of HPV infection during pregnancy and may provide a rationale for the use of HPV vaccines to reduce the incidence of spontaneous abortion and infertility due to preclinical spontaneous abortions.

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

BACKGROUND: Although 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. METHODS: We 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. RESULTS: We found that the spontaneous regression rate of CIN3 was 15,8%, which was strongly associated with the biopsy-cone interval > 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. CONCLUSION: To 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.

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.

Evidence for HPV DNA in the placenta of women who resorted to elective abortion.

BACKGROUND: It is believed that HPV infection can result in the death of placental trophoblasts and cause miscarriages or preterm birth. In clinical cases of placental villi positive for HPV DNA reported by other authors, contamination is suspected in the act of crossing the cervical canal. We analyzed placental samples of women who resorted to elective abortion obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. METHODS: We studied the chorionic villi of the placenta of 64 women who resorted to voluntary termination of pregnancy, in the first trimester. To avoid contamination of the villi by the cervical canal, we analyzed placental samples obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. All samples of chorionic villi were manually selected from the aborted material and subjected to research for HPV DNA. RESULTS: HPV DNA was detected in 10 out of 60 women (16.6%). The HPV DNA identified in the placenta belonged to genotypes 6, 16, 35, 53, and 90. CONCLUSION: The study shows that papillomavirus DNA can infect the placenta and that placenta HPV infection can occur as early as the first trimester of pregnancy.

Progression of CIN1/LSIL HPV Persistent of the Cervix: Actual Progression or CIN3 Coexistence.

Objective: The natural history of the CIN1 lesions is characterized by an elevated rate of spontaneous regression (80%), some authors recognize a capacity to progress to HSIL in 10% of cases, and other authors do not recognize the capacity of progression of LSIL (CIN1). This study was aimed to evaluate the incidence of progression to HSIL (CIN3) in women with a histological diagnosis of LSIL (CIN1). Furthermore, to this end, we studied the histological outcomes of cone specimens collected by the LEEP. Methods: All the data were retrospectively analyzed. All participants underwent a follow-up of 4 years, during which each woman underwent an HPV test and genotyping, cervical cytological sampling, or biopsy every six months. The endpoint was the histological confirmation of CIN3 lesions in any moment during follow-up. Results: Progression to CIN3 occurred in 7 cases (1,5%). Analyzing the histological exams of the cones of the 7 cases that progressed to CIN3, we found the coexistence of CIN1 and CIN3 lesions in all cases. Conclusion: After 4 years of follow-up, only 1.5% (7/475) of the women with LSIL developed CIN3, all within the first two years of follow-up, and were immediately treated. The most likely explanations for "progression" from LSIL to HSIL are (1) actual progression, (2) underdiagnosis of HSIL on initial biopsy, (3) overdiagnosis of HSIL on follow-up biopsy/cone, and (4) CIN3 arose de novo. Analyzing the histological exams of the cones of the 7 cases that progressed to high-grade, we found the coexistence of CIN1 and CIN3 lesions in all cases. Some recent studies have shown that a viral genotype corresponds to different lesions in the same cervix; therefore, CIN1 coexisting with CIN3 does not always indicate progression of CIN1. Other authors have doubted the capacity of LSIL to progress.

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

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 < 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.

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 < 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.

HPV16 persistent infection and recurrent disease after LEEP.

BACKGROUND: About 23% of patients develop CIN2+ after LEEP treatment due to residual or recurrent lesions. The majority of patients with HPV infection were HPV negative before treatment, but 16,4% were still HPV 16 positive after treatment, indicating that conization do not necessarily clear HPV infection rapidly. The aim of this retrospective study was to evaluate the possible correlation existing between the appearance of recurring high-grade lesions and the viral genotype 16, and other risk factors such as residual disease. METHODS: One hundred eighty-two HPV positive patients underwent LEEP for CIN2+. The follow-up post treatment was carried out every 6 months. Abnormal results during follow-up were confirmed histologically and considered recurrent high-grade intraepithelial cervical lesions (CIN2/CIN3 or CIS). Statistical analysis was performed by using the SPSS software package for Windows (version 15.0, SPSS, Chicago, IL, USA). Descriptive statistics are expressed as frequency, arithmetic mean, standard deviation (S.D.) and percentages. We calculated significance (P < 0.5) with the Easy Fischer Test. We calculated the Odds Ratio (OR) of women with peristent HPV 16 infection and positive margin, to have a recurrence. RESULTS: In our study, the rate of persistent infection from HPV 16, after LEEP, was 15.9% (29/182) with 94% (17/18) of the recurring disease occurring within 18 months of follow up. From this study it was found that the persistence of genotype 16 is associated with a greater rate of relapse post-conization of CIN 2+ lesions, with respect to other genotypes. Our study further supports those studies that demonstrate that the risk for residual disease or relapse is not to be overlooked, also when the margins are negative, but persistent HPV infection is present. In our case study, 40% of relapses were in women with negative margin, but with persistent HPV 16 infection. Even more so, the margins involved in HPV16 positive subjects is another prediction factor for relapse. CONCLUSIONS: Our results show the importance of genotyping and that persistent HPV 16 infection should be considered a risk factor for the development of residual/recurrent CIN 2/3.

Sexual Behavior of Women With Diagnosed HPV.

One hundred twenty-one women of reproductive age with suspected human papillomavirus (HPV) infection were studied. HPV-DNA testing was performed to determine HPV positivity and genotype. The Female Sexual Function Index was administrated before and three months after the diagnosis was communicated to the patient. Eighty-six women were HPV-positive and had a significant worsening of sexual function over the next three months. The women receiving information that they were HPV-negative did not experience a worsening of sexual function. Clinicians need to be aware of the possible adverse effects on sexual behavior of the diagnosis of HPV.

Management of ASC-US/HPV positive post-menopausal woman.

BACKGROUND: The aim of our study was to determine which diagnostic course is best to identify women at risk of CIN2+ among post-menopausal women with cytological diagnosis of ASCUS METHODS: We selected women who had been post-menopausal for at least one year , and who had completed the entire diagnostic-therapeutic course that they had undertaken. The sample was divided into two arms: in the first arm, we considered 146 ASCUS positive women who had undergone the HPV test, colposcopy and then underwent more detailed diagnostics by means of LEEP or a scraping of the cervical canal. The second arm was made up of 124 ASCUS positive women who had undergone a vaginal administration of estriolo, the HPV test and colposcopy. Estriol was administered for 5 weeks: the first week one vaginal suppository every evening, the other four weeks the administration was twice a week. Then, the patients underwent colposcopy. In cases of positivity a biopsy was carried out, the patients positive for CIN2+ at the biopsy underwent excisional therapy using LEEP and were followed up. The patients, who were negative at colposcopy or with histological diagnosis of CIN1, were examined again at 1 year. RESULTS: In the first arm the HPV test had an SE of 94%, an SP of 68%, NPV of 99%, and PPV of 28%. The PPV is very low because of the elevated percentage of false positives that the HPV test gave (71%). In the second arm the HPV test maintained its high SE (100%), an SP of 74%, a NPV of 100%, and a PPV of 43%. The use of estrogen increased the specificity of the test. CONCLUSION: It is important to say that the second arm indicates the use of local estrogen therapy only for ASCUS/HPV positive postmenopausal women. Therefore, the HPV test should be used as the first diagnostic possibility in cases of ASCUS in post-menopausal women, associating local estrogen therapy only with HPV positive women.