Search Results (13)

Background: Women treated for cervical intraepithelial neoplasia grade 2 (CIN2) face an increased risk of disease recurrence due to persistent or newly acquired human papillomavirus (HPV) infections, suggesting a potential role for adjuvant HPV vaccination. While a growing body of literature evaluates the outcomes of HPV vaccination following a large loop excision of the transformation zone (LLETZ) for high-grade squamous intraepithelial lesions (CIN2–3), data specifically focused on isolated CIN2 remain limited. This study aims to evaluate the clinical efficacy of the nonavalent HPV vaccine (9vHPV) as an adjuvant strategy to reduce CIN2+ recurrence in women undergoing LLETZ for histologically confirmed, isolated CIN2. Methods: Between November 2017 and November 2024, women undergoing LLETZ for histologically confirmed CIN2 received their first dose of adjuvant 9vHPV within one month of surgery. Patients who achieved double-negative co-testing (Pap test and high-risk HPV DNA test) at the 6-month post-LLETZ follow-up were included in the study group. Conversely, patients with at least one positive test result at 6 months were excluded to rule out residual disease. The study group underwent a subsequent Pap smear at 12 months and a full co-test at 18 months post-surgery; upon achieving negative results through the 18th month, patients returned to the organized screening program. The primary outcome was the recurrence rate, defined as histologically confirmed CIN2+ occurring more than 6 months post-treatment. It was compared against an unvaccinated historical control group treated with LLETZ prior to the study period. The secondary outcome evaluated the prevalence of HPV genotypes at baseline and at the time of recurrence. Results: In the vaccinated group, 3 women (2.03%) experienced CIN2+ recurrence compared to 6 women (5.71%) in the unvaccinated control group. This represents an absolute risk difference of 3.69% and a relative risk reduction of 64.6%, though the difference did not reach statistical significance via Fisher’s exact test (p = 0.165). In the study group, two recurrences were detected at 18 months (associated cytologies: ASC-H and LSIL; genotypes: HPV 51/53 and 16, respectively) and one at four years (cytology: HSIL; genotype: HPV 33/58). In the control group, recurrences occurred at 12 months (n = 3), 18 months (n = 2), and four years (n = 1). Associated cytology revealed HSIL in three cases, ASC-H in one case, LSIL in one case, and ASCUS in the final case. The corresponding HPV genotypes were 16 (two cases), 18, 51, 31 and 56 (co-infection), and one case of high-risk HPV, not further genotyped. Conclusions: Adjuvant 9vHPV administration after LLETZ for isolated CIN2 was associated with a clinically substantial lower absolute recurrence rate (2.03% vs. 5.71%, corresponding to a 64.6% relative risk reduction). Although this reduction did not achieve statistical significance ($p=0.165$) due to our small sample size and a low baseline recurrence rate in this isolated cohort, the effect size is highly comparable to broader CIN2+ studies. The study was likely underpowered to prove statistical significance, and larger multi-center studies are required to confirm the statistical value of adjuvant vaccination specifically in isolated CIN2 lesions. Full article

Background/Objectives: Large loop excision of the transformation zone (LLETZ) is used as a standard treatment for cervical dysplasia. Although obesity is associated with reduced cervical screening participation and may complicate gynecologic procedures, evidence on the impact of body mass index (BMI) on LLETZ outcomes remains limited. This study aimed to evaluate the association between BMI and clinical outcomes after LLETZ, with a particular focus on margin status. Methods: This retrospective single-center cohort study included 1397 patients who underwent LLETZ for cervical dysplasia between January 2010 and December 2024 at the Medical University of Vienna. Patients were categorized as normal-weight (BMI < 25 kg/m²) or overweight/obese (BMI ≥ 25 kg/m²). The primary outcome was margin status. Secondary outcomes included postoperative bleeding, lesion localization, histological findings, HPV status, cone depth, and surgeon status. Results: Overall, 949 patients had a BMI < 25 kg/m² and 448 had a BMI ≥ 25 kg/m². Negative margins were achieved in 984 patients (70.4%), with no significant difference between BMI groups. Postoperative bleeding occurred in 53 patients (3.8%) and was significantly less frequent in patients with BMI ≥ 25 kg/m². Each 5-unit increase in BMI was associated with a 38% reduction in the odds of postoperative bleeding. BMI was not significantly associated with HPV status or histological findings. Conclusions: BMI was not associated with overall margin status after LLETZ, suggesting that overweight and obesity do not adversely affect short-term surgical outcomes in general. Further prospective studies are needed to evaluate long-term outcomes. Full article

Background: Immunosuppressed women are at increased risk of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN 2–3) after excisional treatment, yet long-term comparative data remain limited. Previous studies are often small and heterogeneous, and they rarely compare outcomes directly with immunocompetent populations. This study evaluated the long-term incidence, timing and associated factors of CIN 2–3 recurrence after large loop excision of the transformation zone (LLETZ), stratified by immune status. Methods: We conducted a retrospective cohort study including 283 women treated with LLETZ for CIN 2–3 between 1996 and 2016 at Bellvitge University Hospital in Barcelona, Spain. Of these, 41 were immunosuppressed and 242 immunocompetent. Clinical, histopathological, virological, and immunological variables were extracted from hospital and pathology registries. Kaplan–Meier estimates and Cox proportional hazards models adjusted for immunosuppression status were used to evaluate time-to-recurrence and factors associated with recurrence. Results: At 36 months post-treatment, the probability of residual/recurrent CIN 2–3 was 44% in immunosuppressed women versus 5% in immunocompetent women (HR = 10.42, 95% CI 4.70–23.08, p < 0.001). Recurrence appeared earlier in immunosuppressed women (median 7 vs. 13 months). Persistent high-risk HPV infection at first follow-up (HR = 23.6, 95% CI 5.44–102, p < 0.001) and positive surgical margins (HR = 3.88, 95% CI 1.45–10.3, p = 0.007) were among the factors most strongly associated with recurrence, and advanced immunodeficiency (CD4+ < 200 cells/mm³ or detectable HIV viral load) was associated with earlier recurrences, though this association was not maintained after accounting for immunosuppression status in Cox models. Conclusions: Immunosuppressed women are at significantly higher and earlier risk of residual/recurrent CIN 2–3 after LLETZ. These findings support a risk-adapted, multidisciplinary follow-up integrating gynecologic, infectious disease, and immunologic care. Tailored surveillance and perioperative HPV vaccination may enhance secondary prevention in this high-risk population. Full article

Background/Objectives: This study evaluates the diagnostic performance of DNA methylation testing, alone and in combination with cervical cytology, for high-grade squamous intraepithelial lesion (HSIL) detection. Methods: A prospective study was conducted on 170 high-risk HPV (hr-HPV)-positive women. DNA methylation (QIAsure^®) and cervical cytology were performed prior to cervical large loop excision of the transformation zone (LLETZ). Sensitivity, specificity, and area under the curve (AUC) metrics were calculated, including stratified analyses for HPV16/18 and other hr-HPV genotypes. Results: DNA methylation alone achieved a sensitivity of 69.7%, specificity of 79%, and an AUC of 0.796 for HSIL detection. The combination of cervical cytology and DNA methylation improved sensitivity to 94.7%, specificity to 76.3%, and AUC to 0.860. Stratification by HPV genotype revealed that in HPV16/18-positive cases, DNA methylation alone reached an AUC of 0.790, while the combination with cytology significantly enhanced performance to 0.917. DNA methylation alone demonstrated an AUC of 0.744 for other hr-HPV types, and the combined approach achieved an AUC of 0.849. Specificity for the combined approach was notably higher in HPV16/18-positive women (88.9%) than in other hr-HPV cases (72.4%), whereas the sensitivity of the combined approach was significantly higher in both groups (94.5% vs. 95%, respectively). Conclusions: The integration of DNA methylation with cervical cytology significantly enhances diagnostic accuracy for CIN2+ lesions, especially in HPV16/18-positive cases. However, the comparatively lower AUC and specificity observed in other hrHPV types suggest the need for further optimization to enhance accuracy in non-16/18 infections. These findings support the integration of methylation-based testing with cytology as a valuable triage strategy for improving cervical cancer screening and patient management. Full article

Background: Cervical cancer is one of the most common cancers in women worldwide, with the leading risk factor being high-risk human papillomavirus (HR-HPV); persistent HR-HPV infection leads to cervical dysplasia. With early screening and, if indicated, therapeutic strategies such as a loop electrosurgical excision procedure (LEEP) and large loop excision of the transformation zone (LLETZ), morbidity and mortality in this population are decreasing. However, it is suspected that these procedures may have an impact on sexual dysfunction. Methods: In this single-center prospective longitudinal study, we recruited patients with a high-grade squamous intraepithelial lesion (HSIL) and HR-HPV-positive result and evaluated the impact of LEEP/LLETZ on their sexual life and psychological well-being. All participants received two questionnaires—the Female Sexual Function Index (FSFI) and the Brief Index of Sexual Function-Women (BISF-W)—after diagnosis, before treatment, and three months after the procedure. Results: A total of 40 women aged 28 to 55 years were enrolled. This study showed no significant changes in both the FSFI (F(1,39) = 0.774; p = 0.38) and BISF-W total scores (F(1,39). This study revealed that 32/40 (80%) of participants based on the FSFI either exhibited no change or improved sexual function. Only 3/40 (7.5%) mentioned sexual dysfunction after procedures. This study also found that the mean score for sexual function based on the FSFI was 2.80; p = 0.102. Conclusions: These findings suggest that patients who qualified for LEEP/LLETZ can be reassured that the anxiety they experience prior to treatment is not necessarily justified. This provides evidence of the safety of loop excision procedures in terms of sexual functioning after the procedure. Nevertheless, further studies are needed to analyze the potential risk factors that may contribute to adverse sexual outcomes and to achieve a better understanding of this complex problem. Full article

Background/Objective: Women treated with large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia grade 2-3 (CIN2-3) remain at risk of CIN2-3 and cervical cancer for many years. We assessed the roles of high-risk human papillomavirus (HR-HPV) post-LLETZ, surgical margins, and LLETZ characteristics on the long-term risk of CIN2-3. Methods: A retrospective observational study was performed using data for 432 women with a histological diagnosis of CIN2-3 treated by LLETZ between 1996 and 2020 and followed-up until October 2021 at Hospital Bellvitge in Barcelona, Spain. Age, surgical margins, 6-month HR-HPV status, excision type, and cone volume/dimensions were analyzed in association with the risk of persistent/recurrent CIN2-3. The cumulative probability of persistent/recurrent CIN2-3 was calculated using the Kaplan–Meier and Cox models. Results: Persistent/recurrent CIN2-3 was detected in 7.4%, with over 90% found within 5 years post-LLETZ. Predictors of persistent/recurrent CIN2-3 were HR-HPV (HR = 7.36, 95% CI = 3.55–15.26), involved margins (HR = 3.94, 95% CI = 1.68–9.25), uncertain margins (HR = 4.42, 95% CI = 1.55–12.55), and age ≥ 35 years (HR = 2.92, 95% CI = 1.19–7.13). Type 3 excision (p = 0.035) and cone length (p = 0.010) correlated with clear margins. The negative predictive value (NPV) of both negative HR-HPV and clear margins post-LLETZ was 98.7%. Conclusions: The combination of negative HR-HPV and clear margins post-LLETZ provides stronger reassurance against the risk of persistent/recurrent CIN2-3 than do LLETZ characteristics. However, larger excisions in older women likely reduce the risk of involved margins. Close surveillance, including repeat HR-HPV testing in the first 5 years post-LLETZ, is crucial. Full article

Background/Objectives: The study aimed to investigate the efficacy of medication treatment with glycyrrhizinic acid for cervical intraepithelial neoplasia (CIN) 1 lesions. Methods: Women with histologically confirmed CIN 1 in cervical biopsies were included in the prospective study. Participants of the study group used glycyrrhizinic acid spray (Epigen spray) topically 10 days (Epigen 10-day subgroup) or 20 days (Epigen 20-day subgroup) per month for 6 months. Women in the control group had no treatment. There were two follow-up visits 6 months apart. All patients were screened for human papillomavirus (HPV) before enrollment and during the first follow-up visit. Results: There were 50 patients in the Epigen group and 50 patients in the control group. At the first follow-up visit, in the histological findings, progression to CIN 2+ was 6.7% in the Epigen 20-day subgroup, 31.1% in the control group, and the persistence of CIN 1 was 86.7% in the Epigen 20-day subgroup and 62.2% in the control group, p = 0.03. Large loop excision of the transformation zone (LLETZ) was statistically significantly more frequent in the control group after the first follow-up visit (10% in the Epigen 20-day subgroup vs. 30% in the control group, p = 0.032). No such relationships were found during the second follow-up visit. Conclusions: The vaginal spray of the glycyrrhizinic acid used 20 days per month appears to decrease the risk of the progression of CIN 1 lesions, with the need to perform LLETZ. However, a similar effect is not observed after stopping usage. Full article

Background: The aim of this study is to evaluate the distribution of the histological results of the endocervical curettage (ECC) at large loop excision of the transformation zone (LLETZ) as well as the additional diagnostic information and its impact on further clinical treatment recommendations in accordance with national guidelines. The ECC in addition to LLETZ can serve to detect (pre)cancerogenic lesions above the endocervical cone margin, although its predictive value as well as diagnostic accuracy remains vague due to limited studies performed on this topic. Methods: In this retrospective cohort study, 1121 patients who underwent LLETZ and concomitant ECC during a twelve-year period (2009–2021) were analyzed. The main outcome parameters were the histological diagnosis and incidence of adequate or inadequate ECC specimens. Results: In 1.7% of the specimens, ECC performed at the completion of LLETZ yielded additional diagnostic information. The histological result of the ECC had an impact on subsequent therapeutic approach in 2 of the 1121 patients (0.2%). Furthermore, a negative ECC yielded a low negative predictive value (NPV) of 43.8% for the detection of residual disease. Conclusions: As current guidelines increasingly support the performance of an HPV test six months after LLETZ as an indicator of treatment success irrespective of the margin status, the routine performance of an ECC at LLETZ remains questionable. Full article

Background: Female sex workers (FSWs) are at high risk for sexually transmitted infections (STIs), including infection with human papillomavirus (HPV) and cervical cancer due to occupational exposure. The objective of this study was to estimate the prevalence of HPV, HPV types, and precancerous lesions of the cervix among FSWs in Cameroon. Material and Methods: In this cross-sectional study, FSWs in Cameroon aged 30 years and above were screened for cervical cancer using high-risk HPV testing and genotyping and visual inspection with acetic acid and Lugol’s iodine (VIA/VILI) enhanced using digital cervicography (DC) simultaneously. Those who were positive for VIA/VILI-DC were provided treatment with thermal ablation (TA) immediately for cryotherapy/TA-eligible lesions while lesions meeting the criteria for large loop excision of the transformation zone (LLETZ) were scheduled at an appropriate facility for the LLETZ procedure. HPV-positive FSWs without any visible lesion on VIA/VILI-DC were administered TA. Bivariate analyses were conducted to compare demographic and clinical characteristics. Crude and adjusted logistic regression models were computed for HPV infection status and treatment uptake as outcomes in separate models and their ORs and 95% confidence intervals (95% CI) were reported. Results: Among the 599 FSWs aged 30 years and older that were screened for HPV and VIA/VILI-DC, 62.1% (95% CI: (0.58–0.66)) were positive for one or more HPV types. HPV type 51 had the highest prevalence (14%), followed by types 53 (12.4%) and 52 (12.2%). Type 18 had the lowest prevalence of 2.8% followed by type 16 with 5.2%. In the multivariable model, HIV-positive FSWs were 1.65 times more likely to be infected with HPV compared to their HIV-negative counterparts (AOR: 1.65, CI: 1.11–2.45). A total of 9.9% of the 599 FSWs were positive for VIA/VILI-DC. Conclusion: The prevalence of HPV infection among FSWs in Cameroon is higher than the worldwide pooled FSW prevalence. HPV types 51 and 53 were the most prevalent, while types 18 and 16 were the least prevalent. HIV status was the only variable that was significantly associated with infection with HPV. Full article

The aim of this study was to evaluate the endocervical margin status according to transformation zone (TZ) and high-risk HPV (hr-HPV) subtype in specimens with cone length ≤ 10 mm versus > 10 mm to provide data for informed decision making and patients counseling especially for women wishing to conceive. In this retrospective cohort study, 854 patients who underwent large loop excision of the transformation zone during a nine-year period (2013–2021) for cervical disease were analyzed. The main outcome parameters were excision length, histological result, TZ type, HPV subtype and endocervical margin status. A subgroup analysis was performed according to excision length, with a cut-off value of 10 mm. A two-step surgical procedure was performed in case of an excision length of > 10 mm. The overall rate of positive endocervical margins irrespective of excision length was 17.2%, with 19.3% in specimens with ≤ 10 mm and 15.0% with > 10 mm excision length. Overall, 41.2% of women with a visible TZ and HPV 16/hr infection and 27.0% of women with HPV 18 received an excisional treatment of > 10 mm length without further oncological benefit, respectively. In contrast, assuming that only an excision of ≤ 10 mm length had been performed in women with visible TZ, the rate of clear endocervical margins would have been 63.7% for HPV 16/hr infections and 49.3% for HPV 18 infections. In conclusion, the decision about excision length should be discussed with the patient in terms of oncological safety and the risk of adverse pregnancy events. An excision length > 10 mm increases the number of cases with cervical tissue removed without further oncological benefit, which needs to be taken into account in order to provide an individual therapeutic approach. Furthermore, HPV 18 positivity is related to a higher rate of positive endocervical margins irrespective of TZ. Full article

The objective of this research is to evaluate cervical regeneration after large loop excision of the transformation zone (LLETZ) through the identification of a new sonographic reference point at the level of the uterine margins. In the period March 2021–January 2022, a total of 42 patients affected by CIN 2–3 were treated with LLETZ at the University Hospital of Bari (Italy). Before performing LLETZ, cervical length and volume were measured with trans-vaginal 3D ultrasound. From the multiplanar images, the cervical volume was obtained using the Virtual Organ Computer-aided AnaLysis (VOCAL™) program with manual contour mode. The line that connects the points where the common trunk of the uterine arteries reaches the uterus splitting into the ascending major branch and the cervical branch was considered as the upper limit of the cervical canal. From the acquired 3D volume, the length and the volume of the cervix were measured between this line and the external uterine os. Immediately after LLETZ, the removed cone was measured using Vernier’s caliper, and before fixation in formalin, the volume of the excised tissue was evaluated by the fluid displacement technique based on the Archimedes principle. The proportion of excised cervical volume was 25.50 ± 17.43%. The volume and the height of the excised cone were 1.61 ± 0.82 mL and 9.65 ± 2.49 mm corresponding to 14.74 ± 11.91% and 36.26 ± 15.49% of baseline values, respectively. The volume and length of the residual cervix were also assessed using 3D ultrasound up to the sixth month after excision. At 6 weeks, about 50% of cases reported an unchanged or lower cervical volume compared to the baseline pre-LLETZ values. The average percentage of volume regeneration in examined patients was equal to 9.77 ± 55.33%. In the same period, the cervical length regeneration rate was 69.41 ± 14.8%. Three months after LLETZ, a volume regeneration rate of 41.36 ± 28.31% was found. For the length, an average regeneration rate of 82.48 ± 15.25% was calculated. Finally, at 6 months, the percentage of regeneration of the excised volume was 90.99 ± 34.91%. The regrowth percentage of the cervical length was 91.07 ± 8.03%. The cervix measurement technique that we have proposed has the advantage of identifying an unequivocal reference point in 3D cervical measurement. Ultrasound 3D evaluation could be useful in the clinical practice to evaluate the cervical tissue deficit and express the “potential of cervical regeneration” as well as provide the surgeon useful information about the cervical length. Full article

Data on non-surgical treatment approaching persistent cervical intraepithelial neoplasia (CIN) are scarce. Retrospective analysis suggest high efficacy of topical treatment with trichloroacetic acid (TCA). This prospective phase II study set out to investigate the efficacy of a single application of 85% TCA in the treatment of CIN I/II. Patients with CIN I/II were treated a single time with 85% TCA. After three and six months colposcopic, histologic, and HPV evaluation was performed. The primary endpoint was treatment efficacy defined as complete histologic remission six months after treatment. The secondary endpoint was HPV clearance six months after treatment. A total of 102 patients with CIN I/II were included into this trial. Complete histologic remission rates were 75.5% and 78.4% three and six months after TCA treatment, respectively. Clearance rates of HPV 16, 18 and other high risk types were 76.5%, 91.7%, 68.7% after six months, respectively. Side effects of TCA were mild and lasted usually less than 30 min. This is the first prospective trial reporting high histologic complete remission rates in patients with CIN I/II after a single 85% TCA treatment. In the future, TCA may represent an effective and feasible non-surgical treatment approach for CIN. Full article

Colposcopy is often used in follow-up after treatment for cervical intraepithelial neoplasia (CIN) despite its marked inter-observer variability and low sensitivity. Our objective was to assess the role of colposcopy in post-treatment follow-up in comparison to hrHPV (high-risk human papillomavirus) testing, cytology, and cone margin status. Altogether, 419 women treated for histological high-grade lesion (HSIL) with large loop excision of the transformation zone (LLETZ) attended colposcopy with cytology and hrHPV test at six months. Follow-up for recurrence of HSIL continued for 24 months. Colposcopy was considered positive if colposcopic impression was recorded as high grade and cytology if HSIL, ASC-H (atypical squamous cells, cannot exclude HSIL), or AGC-FN (atypical glandular cells, favor neoplasia) were present. Overall, 10 (10/419, 2.4%) recurrent HSIL cases were detected, 5 at 6 months and 5 at 12 months. Colposcopic impression was recorded at 407/419 6-month visits and was positive for 11/407 (2.7%). None of them had recurrent lesions, resulting in 0% sensitivity and 97% specificity for colposcopy. Sensitivity for the hrHPV test at 6 months was 100% and specificity 85%, for cytology 40% and 99%, and for margin status at treatment 60% and 82%, respectively. While the hrHPV test is highly sensitive in predicting recurrence after local treatment for CIN, colposcopy in an unselected population is not useful in follow-up after treatment of CIN. Full article