Diagnostic cervical excision in patients with HPV positivity, cytological abnormalities- and preoperative cervical stenosis.

AIM: There is currently no protocol for classifying patients with HPV persistence and preoperative stenosis of the cervical canal. This has a significant impact on cytology results, colposcopy results and the possibility of obtaining reliable cervical histology outcomes. Our analysis clearly shows that colposcopy and cytology underestimate the histological results in patients with limited visibility due to the presence of a type 3 transformation zone (TZ). Our analysis revealed a significant discrepancy between the colposcopy and cytology results and the histological outcomes. Insufficient colposcopy led to the underdiagnosis of dysplastic lesions in patients with a type 3 TZ and cervical stenosis. In the case of repeated cytological abnormalities and inadequate colposcopy examination, it is crucial to perform a diagnostic conization to exclude high-grade dysplastic changes and cervical carcinoma. METHODS: We conducted a retrospective analysis of 1,021 conizations performed in tertiary care hospital in Wolfsburg, Germany between 2014 and 2020. Of these surgical procedures, 89 were diagnostic conizations. In our analysis, we defined diagnostic conization as a procedure performed when there is HPV persistence and repeated cytologic abnormalities in combination with a type 3 TZ, and when it is not possible to retrieve a relevant cervical histology sample. RESULTS: In this period, 8.7% of all conizations were diagnostic excisions. We found histological abnormalities in 48 of 89 patients (53.9%). The histological examination of the excised cone revealed high-grade cervical intraepithelial neoplasia (CIN/HSIL) in 9 patients (10.1%) and CIN 2+ (HSIL) in 23 out of the 89 patients (25.8%). Two cases of early-stage cervical carcinoma (FIGO IA1 and FIGO IA2) were confirmed (2.3%). CONCLUSION: Patients with cervical stenosis, high-risk HPV persistence and repeated cytological abnormalities are at high risk of undetected high-grade cervical dysplasia. Histologic confirmation must be ensured in this patient consultation and this can be achieved by performing diagnostic excisions.

Analysis of the clinical characteristics and surgical methods of high-grade squamous intraepithelial lesions of the cervix in postmenopausal women: A retrospective case study.

The purpose of this study was to thoroughly evaluate the clinical features and surgical options for high-grade squamous intraepithelial lesions (HSIL) in postmenopausal women. A total of 308 patients diagnosed with HSIL through colposcopic cervical biopsy and endocervical curettage were included. Their clinical characteristics, surgical treatments, and postoperative pathology were analyzed. Key findings include: 1. Patients with positive preoperative thinprep cytologic test (TCT) results and postoperative pathology indicating HSIL or squamous cell carcinoma (≥HSIL) were significantly more frequent than those with negative preoperative TCT results (P < .05). 2. Univariate analysis indicated significant impacts of TCT, human papillomavirus (HPV) type, transformation zone (TZ) location, and surgical technique on postoperative pathology (P < .05). 3. Logistic regression analysis confirmed significant influences of TCT, HPV type, TZ location, and surgical method on postoperative pathology outcomes (P < .05), showing that each unit increase in TZ raised the probability of ≥HSIL in postoperative pathology by 49.7%. In surgical comparisons, cold knife conization (CKC) and extrafascial hysterectomy resulted in 8.379 and 4.427 times higher probabilities of ≥HSIL in postoperative pathology, respectively, compared to loop electrosurgical excision procedure (LEEP). 4. Surgical methods significantly influenced margin results (P < .05). After LEEP, 17.5% of cases had positive margins, compared to 9.4% after CKC, and 3.7% after extrafascial hysterectomy, indicating the highest rate of positive surgical margins occurred with LEEP. 1. Combined TCT and HPV screening is crucial for cervical cancer prevention, early detection, and management in postmenopausal women. Women with positive results for both TCT and HPV should undergo colposcopic cervical biopsy and endocervical curettage. 2. For patients with TZ3, CKC is the recommended surgical option. 3. CKC is the preferred treatment for postmenopausal women with HSIL, as it effectively diagnoses and treats the lesion, showing superior outcomes in managing postmenopausal HSIL.

Oncological outcomes post transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma, a single-centre retrospective Australian study.

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.

Comparison of Long-Term Outcomes of Surgical Treatment of Human Papillomavirus-Dependent Neoplastic Lesions in Patients With Chronic Immunosuppression After Allogenic Organ Transplantation and Patients With Primary or Acquired Immunodeficiency-A One-Center Experience.

Immunodeficiency predisposes to severe manifestations of human papillomavirus (HPV) infection, including extensive, recalcitrant anogenital lesions and their progression towards carcinomas. This holds for primary and acquired immunodeficiencies, and post-transplant immunosuppressive therapy. About 50% to 90% of patients receiving chronic immunosuppression after allogenic transplantation develop HPV-associated lesions within 4 to 5 years, comprising 10% to 15% of patients presenting with (pre)cancerous HPV-dependent anogenital lesions. Immunodeficiency is one of the highest risk factors associated with severe clinical manifestations of HPV-associated cancers. The primary objective of this work is to compare the long-term therapeutic effectiveness of surgical intervention for HPV-dependent lesions in transplant recipients undergoing chronic immunosuppression and patients burdened with primary or acquired immunodeficiencies. Two groups of 30 patients (selected for most extensive presentations of HPV-dependent neoplastic anogenital lesions), who underwent surgical treatment of these lesions were followed up for 3 to 5 years. The first group comprised patients who qualified and underwent kidney or liver transplantation (10 for a rare disease indication) and are under chronic immunosuppressive regimens. The second group comprised patients burdened by primary or acquired immunodeficiency (15 each). The recurrence rate in the follow-up period was the primary compared parameter. The recurrence rate was higher in the second group, amounting to >15%. For the first group a <5% recurrence rate was observed for recipients without rare disease indications, compared to <15% for recipients with such indications. The importance of rapid surgical intervention and the need for postoperative monitoring for recurrence is highlighted. Chronic immunosuppression demonstrates high relative safety and efficacy in terms of HPV-dependent anogenital lesion recurrence.

Focused ultrasound versus the loop electrosurgical excision procedure to treat women with cervical high-grade squamous intraepithelial lesions under 40: a retrospective study.

BACKGROUND: This study aimed to compare the efficacy of focused ultrasound (FUS) and the loop electrosurgical excision procedure (LEEP) for the treatment of cervical high-grade squamous intraepithelial lesions (HSILs) among women of reproductive age. METHODS: Case records of patients aged < 40 years who were treated for cervical HSILs using either FUS or LEEP from September 1, 2020 to May 31, 2022 were retrospectively reviewed. Patients were followed up for cure, recurrence, human papillomavirus (HPV) clearance, and complications within 1 year of treatment. Odds ratios and 95% confidence intervals were determined using univariate and multivariate logistic regression models to analyze the association between disease evidence or HPV clearance and treatment modalities or other covariates. RESULTS: Of the 1,054 women who underwent FUS or LEEP, 225 met our selection criteria. Among the selected women, 101 and 124 received FUS and LEEP, respectively. There was no significant difference between the FUS and LEEP groups in the cure rate during the 3-6 months of follow-up (89.11% vs. 94.35%, P = 0.085) and recurrence rate during the 6-12 months follow-up (2.22% vs. 1.71%, P = 0.790). Both groups exhibited enhanced cumulative HPV clearance rates; however, the rates were not significantly different between the FUS and LEEP groups (74.23% vs. 82.79%, P = 0.122 during the 3-6 months follow-up; 84.95% vs. 89.17%, P = 0.359 during the 6-12 months follow-up). Furthermore, the incidence of complications caused by the FUS and LEEP techniques was comparable (5.0% vs. 5.6%, P = 0.818). CONCLUSIONS: We found that FUS and LEEP have similar efficacy, safety, and reliability in treating women (aged < 40 years) with HSILs.

Sensitive MRD Detection from Lymphatic Fluid after Surgery in HPV-Associated Oropharyngeal Cancer.

PURPOSE: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification. EXPERIMENTAL DESIGN: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, extranodal extension (ENE), and composite definitions of high-risk pathology. We then created a machine learning model, informed by lymph MRD and clinicopathologic features, to compare with progression-free survival (PFS). RESULTS: Postoperative lymph was enriched with cf-HPV compared with plasma (P < 0.0001) and correlated with pN2 stage (P = 0.003), ENE (P < 0.0001), and trial-defined pathologic risk criteria (mean AUC = 0.78). In addition, the lymph mutation number and variant allele frequency were higher in pN2 ENE (+) necks than in pN1 ENE (+) (P = 0.03, P = 0.02) or pN0-N1 ENE (-) (P = 0.04, P = 0.03, respectively). The lymph MRD-informed risk model demonstrated inferior PFS in high-risk patients (AUC = 0.96, P < 0.0001). CONCLUSIONS: Variant and cf-HPV quantification, performed in 24-hour postoperative lymph samples, reflects single- and multifeature high-risk pathologic criteria. Incorporating lymphatic MRD and clinicopathologic feature analysis can stratify PFS early after surgery in patients with HPV (+) head and neck cancer. See related commentary by Shannon and Iyer, p. 1223.

From planned neck dissection to PET response to circulating tumour DNA: changes in post-treatment assessment of HPV-driven oropharyngeal cancer†.

INTRODUCTION: Circulating tumour human papillomavirus DNA (ctHPVDNA) is an emerging tool to assess post-treatment response in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Its use is not a standard practice, however, with interval F-18 FDG PET/CT and fiberoptic examination preferred. Post-treatment PET/CT at 3 months has a low positive predictive value (PPV), especially in patients with HPV+ OPSCC treated with (chemo)radiation therapy (CRT). We aimed to compare 3-6 month post-treatment PET/CT and ctHPVDNA test results to determine the most effective option for post-treatment response assessment. METHODS: Patients with HPV+ OPSCC that underwent commercially available ctHPVDNA blood testing after curative intent treatment were identified. Demographic, clinical, treatment, surveillance and oncologic outcome information were collected for each patient. Specificity and false positive rate were calculated for post-treatment PET/CT and ctHPVDNA. RESULTS: 80% of patients had Stage I disease. 52% of the population was treated with definitive chemoradiation (43%) or accelerated radiation (9%), with the remaining patients treated with transoral robotic surgery (TORS) +/- risk-adapted adjuvant therapy. In total, 25 patients underwent ctHPVDNA testing and PET/CT at 3-6 months after finishing treatment. At 3-6 months post-treatment, specificity of ctHPVDNA and PET/CT was 96% and 56%, correlating to false positive rates of 4% and 44%, respectively. CONCLUSIONS: ctHPVDNA is more reliable than PET/CT following treatment in patients with HPV+ OPSCC, and its incorporation in post-treatment response assessment will decrease the rate of anxiety over persistent disease and lead to a decrease in unnecessary medical procedures, including completion of neck dissection.

Surgical treatment of 186 sinonasal inverted papillomas and analysis of the immunohistochemical and molecular features associated with recurrences.

INTRODUCTION: Inverted papillomas (IP) are benign epithelial tumors with a tendency to be locally invasive and with disposition to recur. The aim of our study is to present the results of IP treatment, considering pathological, immunohistochemical and molecular features of recurrence. MATERIAL AND METHODS: From 1978 to 2020, 186 sinonasal IPs surgeries corresponding to 152 patients were treated in our center. We performed a pathology evaluation of all the recurrent cases reviewing the histological diagnosis, the presence of mixed component other than IP, the koilocytic changes, the p16 over expression and HPV-DNA detection. RESULTS: Overall recurrence rate was 19 % (35/186). The 35 IP recurrences correspond to 22 patients, 9 of whom presented a single recurrence (single recurrence group) while 13 of them presented more than one recurrence (multi-recurrent group). Immunohistochemical analysis showed a higher percentage of p16 overexpression (54 % vs 33 % p = 0.415) and HPV-DNA presence (23 % vs 0 % p = 0.240) in the multi-recurrent group compared with single recurrence group. In addition, the revision showed more IP with exophytic papilloma focus (38 vs 22 % p = 0.648) and a higher proportion of IP with koilocytotic changes (61 % vs 22 % p = 0.099) in the multirecurrent group. There is no significant difference between groups in our results. CONCLUSION: The analysis of our patients may differentiate between two groups with recurrent papillomas. A single recurrence group where the cause of recurrence is probably an anatomical problem related to an incomplete resection, and a second pattern, the multi-recurrence group, where HPV infection may be the main cause of recurrence.

Effects of human papillomavirus and LEEP on sexual function.

BACKGROUND: Human papillomavirus (HPV) infection is the most common sexually transmitted viral infection in humans. AIMS: We evaluated the sexual function of human papillomavirus positive patients after colposcopy and loop electrosurgical excision procedure (LEEP). METHODS: This study enrolled 344 patients with an HPV infection detected on routine screening in 2020-2022. Sexual function was evaluated using the Female Sexual Function Index (FSFI), which consists of six sections: desire, arousal, lubrication, orgasm, satisfaction, and pain. RESULTS: The mean age of the 344 HPV-positive patients was 37.2 ± 8.2 years, and 28.2% of them were unmarried. Colposcopy, cervical biopsy, and LEEP were performed in 251 (73.0%), 189 (54.9%), and 42 (12.2%) patients, respectively. The sexual history and FSFI scores of the patients were recorded. The total and individual parameter scores on the FSFI decreased significantly after colposcopy. Similarly, the total and individual parameter scores on the FSFI were lower at 8 weeks after LEEP compared to those before LEEP. CONCLUSION: Cancer-related fear and anxiety and LEEP may cause sexual dysfunction in HPV-positive patients.

Neck scar perception after neck dissection in HPV-associated oropharyngeal squamous cell carcinoma.

IMPORTANCE: While there has been an increased understanding of the impact of visible neck scars in some patients with certain diseases, this has not yet been explored in the HPV+ OPSCC population. OBJECTIVE: To understand patients' perception of their scar and the impact on their quality of life (QOL) at least 6 months after neck dissection (ND) for HPV+ oropharyngeal squamous cell carcinoma (OPSCC). DESIGN, SETTING, AND PARTICIPANTS: In this retrospective case-control study, patients who underwent primary transoral robotic surgery (TORS) and ND for HPV+ OPSCC between 2016 and 2021 at a single tertiary care center were identified. Data analysis was performed in January 2022. MAIN OUTCOMES AND MEASURES: Dermatology Life Quality Index was modified (mDLQI) to assess patients' perceptions of their scars. The primary outcome was the mean mDLQI survey score with higher scores corresponding to worse perceptions. Three questions adapted from the Self-Consciousness Scale (SCS) were also included to assess awareness of appearance. All questions were scaled on a 0-3 Likert Scale. Tweedie generalized linear model was used to understand the relationship between mDLQI score and patient- and procedure-specific factors (including the three SCS survey questions). An additional exploratory logistic regression was performed to understand the risk factors for clinically significant mDLQI score change. RESULTS: A total of 67 patients (response rate 57 %) completed the survey with a mean mDLQI survey score of 0.84 (max 30). Although there was a statistically significant negative association between private insurance and mDLQI survey score (95 % Confidence Interval [CI]: -2.72 - -0.38), and a positive association between the SCS score and mDLQI survey score (95 % CI: 0.23-0.81) (p < 0.05), these variables were not found to be risk factors for a clinically significant difference in mDLQI on multivariable analysis. CONCLUSION: The majority of patients felt their neck scars did not interfere with their daily lives. Patient perceptions of neck scars were consistent despite differing patient characteristics and treatment regimens.

HPV E6/E7 mRNA combined with thin-prep cytology test for the diagnosis of residual/recurrence after loop electrosurgical excision procedure in patients with cervical intraepithelial neoplasia.

To evaluate the diagnostic value of combining HPV E6/E7 mRNA testing with Thin-Prep cytology (TCT) for residual/recurrence detection, a total of 289 patients who underwent loop electrosurgical excision procedure (LEEP) for high-grade cervical lesions were included. Patients were followed up at different time points, and residual/recurrent lesions were confirmed through vaginoscopy. TCT, HPV-DNA, and HPV E6/E7 mRNA tests were conducted. Diagnostic performance, including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy, was assessed. Among the patients, 76 cases showed residual lesions/recurrence, while 213 cases showed no residual/recurrence. Positive margins in the cervical-vaginal and cervical canal areas were associated with a higher risk of residual/recurrence. The combined HPV E6/E7 mRNA and TCT test showed higher diagnostic efficacy than individual tests at 6-, 12-, and 24-months follow-up. The combined test consistently demonstrated higher specificity and sensitivity, with significantly larger area under the curve (AUC) values compared to the individual tests.

Safety, feasibility, and short-term-outcome of anal endoscopic submucosal dissection for anal intraepithelial neoplasia: an option for focal lesions?

BACKGROUND: Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive anal cancer. AIN 2 (p16 positive) and AIN 3 are of high risk and should be treated because progression rates to anal cancer are around 10% and treatment significantly reduces this risk. The correct treatment is still a matter of debate. Human papilloma virus (HPV) plays a role in the development of AIN. Our aim was to assess anal endoscopic dissection (aESD) as an intervention for AIN3. METHODS: We retrospectively evaluated patients who underwent aESD for AIN 3 between December 2017 and March 2023. The interventional technique itself (duration, complications, size of specimen) and patient outcomes (recurrence, progression to anal cancer, re-intervention) were analyzed. RESULTS: Fifteen patients with a median age of 52 years (23-78) underwent aESD for AIN 3. All tested specimens were positive for HPV. Median duration of intervention was 56.1 min, one delayed postinterventional bleeding occurred, and specimen size was 12.05 cm2. Median follow-up was 11.17 months. Three recurrences (20%) appeared: one was resected via biopsy and two were again treated with aESD. There was no progression to invasive anal cancer in the follow-up period. CONCLUSIONS: Anal endoscopic submucosal dissection seems to be a safe and feasible treatment for AIN. Recurrences are seldom and can be treated again with the same method. Nevertheless, indications for resection in comparison to radiofrequency ablation, pharmacological therapy, and watch-and-wait strategy are still unclear. TRIAL REGISTRATION: Ethics commission of Salzburg, Austria, EK-Nr. 1056/2023. Keywords: Endoscopic submucosal dissection, anal intraepithelial neoplasia, anal cancer.

Role Of CO2 Laser & Microdebrider In The Treatment Of Juvenile Onset Recurrent Respiratory Papillomatosi.

OBJECTIVE: To compare the efficacy of two main treatment modalities of microdebrider and carbon dioxide laser excision for juvenile onset recurrent respiratory papillomatosis. Methods: The retrospective study was conducted in May 2021 at the Combined Military Hospital, Kharian, Pakistan, and comprised data from July 1, 2007, to January 31, 2020, of patients of either gender aged 2-12 years who were treated for juvenile onset recurrent respiratory papillomatosis either with microdebrider excision in group A or carbon dioxide laser excision in group B. Extent and severity of disease was documented as per the Derkay-Coltrera grading system. Data was analysed using SPSS 20. RESULTS: Of the 39 patients, 23(59%) were girls and 16(41%) were boys. The overall mean age at the time of procedure was 6.62±2.06 years. Group A had 22(56.4%) subjects; 15(68.2%) girls and 7(31.8%) boys, while group B had 17(43.6%) cases; 8(47%) girls and 9(53%) boys. The mean operative time for group A was 40.91±11.50 minutes and for group B it was 60.59±19.51 minutes. Postoperative breathing and oedema status was better for group A (p<0.05), while there was no significant difference regarding postoperative pain, residual disease and repeat surgeries (p>0.05). CONCLUSIONS: Microdebrider was found to be superior to carbon dioxide laser excision in the treatment of juvenile onset recurrent respiratory papillomatosis.

Evaluation of the clinical efficacy of vaginal treatment options for persistent high-risk human papillomavirus infection after excisional treatment of cervical high-grade squamous intraepithelial lesions: a systematic review and Bayesian network meta-analysis.

BACKGROUND: To evaluate the clinical efficacy of different vaginal administration on cervical persistent high-risk human papillomavirus (HR-HPV) infection after excisional treatment for high-grade squamous intraepithelial lesions (HSIL). METHODS: Six databases (PubMed, EmBase, Cochrane Central, China Knowledge Network database, China Biomedical Literature Service, and WanFang database) were searched to collect randomized controlled trials (RCTs) of various types of vaginal administration compared to no treatment on persistent HR-HPV infection after HSIL excisional treatment, and comprehensive analysis of the clearance of different drugs on HR-HPV was performed using Bayesian reticulation meta-analysis. RESULTS: The study analyzed the efficacy of eight interventions, including Interferon, Baofukang, Paiteling, Bletilla striata Sanhuang Powder, Lactobacilli vaginal capsules, Fuanning + Interferon, Interferon + Lactobacilli vaginal capsules, and Interferon + Baofukang, on the clearance of HR-HPV after excisional treatment through pooling and analyzing data from 52 RCTs. The results of the study demonstrated that Interferon + Lactobacilli vaginal capsules [OR 16.0 (95% CIs 8.1-32.0)], Interferon + Fuanning [OR 16.0 (95% CIs 1.1-52.0)], and Interferon + Baofukang [OR 14.0 (95% CIs 6.8-28.0)] were all found to significantly improve postoperative HR-HPV clearance rates when compared to no treatment. Furthermore, when studies with high-risk bias were excluded, Interferon + Lactobacilli vaginal capsules [OR 8.6 (95% CIs 4.7-19.0)] and Interferon + Baofukang [OR 22.0 (95% CIs 8.7-59.0)] were still found to be positively associated with increased postoperative HR-HPV clearance rate. Additionally, the study´s results also indicate that Interferon + Baofukang was effective in enhancing the postoperative HR-HPV clearance rates, mainly when the studies were restricted to a follow-up period of at least 12 months [OR 9.6 (95% CIs 2.9-34.0)]. However, it is important to note that the majority of the trials (29 out of 52, 51.6%) were rated as moderate to high risk of bias, and the certainty of the evidence was moderate to very low. CONCLUSION: The application of various forms of vaginal administration, except for individual use of Lactobacilli vaginal capsules, is more efficacious than no treatment in patients with cervical persistent HR-HPV infection after excisional treatment. However, all of the estimates of the effect size for change in the efficiency of HR-HPV clearance are uncertain. Our confidence in effect estimates and ranking of treatments is low, which needs larger, more rigorous, and longer follow-up RCTs to resolve.

Management of Recurrent HPV-Positive Oropharyngeal Squamous Cell Carcinoma: a Contemporary Review.

PURPOSE OF REVIEW: To review the impact of contemporary treatment strategies on salvage outcomes in patients with recurrent human papilloma virus-positive oropharyngeal squamous cell carcinoma (HPV + OPSCC). RECENT FINDINGS: Secondary to HPV, changes in disease biology have impacted primary treatments and subsequent approaches to patients with recurrence. With treatment strategies more inclusive of upfront surgery, the characteristics of patients with recurrence HPV + OPSCC have been further redefined. Less invasive endoscopic surgical approaches such as transoral robotic surgery (TORS), and the continued refinement of conformal radiotherapy techniques, have improved treatment options for patients with recurrent HPV + OPSCC. Systemic treatment options have continued to expand including potentially effective immune-based therapies. Effective surveillance with systemic and oral biomarkers offers hope of earlier detection of recurrence. Management of patients with recurrent OPSCC remains difficult. Modest improvements in salvage treatment have been observed within the HPV + OPSCC cohort largely reflecting disease biology and improved treatment techniques.

Long-Term Follow-up of Parenteral Bevacizumab In Patients with Recurrent Respiratory Papillomatosis.

OBJECTIVE: The clinical course of recurrent respiratory papillomatosis (RRP) varies from spontaneous remission to severe airway obstruction with wide variability in recurrence. Standard treatment involves debulking to improve voice and/or breathing. Non-surgical therapies are emerging in hopes of non-operative disease control. This retrospective review analyzes long-term safety, efficacy, and durability of clinical control in the largest reported series of parenteral bevacizumab in adults with RRP. METHODS: Twenty-three patients with known RRP who have been receiving off-label systemic bevacizumab were included. Dosage, infusion interval, number of cycles, debulking requirements, subjective outcomes, adverse events, and reasons for treatment termination were investigated. RESULTS: Patients have been followed for an average of 791.43 (21-1468) days. The most common starting dosing regimen was 15 mg/kg at 3 weeks in 11 followed by 10 mg/kg at 6 weeks intervals in 6 individuals. Long-term maintenance dosage varied with the least intensive regimen being 10 mg/kg at 14-week intervals. Subjective improvement of voice and/or breathing was reported in 18/23 subjects. The median time for patients that needed a procedure after treatment was 634 days. Procedures after infusions decreased from 3.08 ± 2.48 procedures in the year prior to 0.52 ± 1.12 during systemic Bevacizumab, and to 0.86 ± 2.05 after stopping bevacizumab. Therapy termination occurred in 8 subjects where only 3 were due to adverse events. CONCLUSION: Parenteral bevacizumab remains a well-tolerated treatment for patients with recalcitrant RRP. There appears to be a durable reduction in the frequency of debulking surgery requirements although on a maintenance regimen. Laryngoscope, 133:2725-2733, 2023.

Aggressive recurrent respiratory papillomatosis: A series of five consecutive patients successfully treated with adjuvant intravenous bevacizumab. A single Belgian academic center experience.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a currently incurable benign neoplasm caused by human papilloma virus (HPV) infection. It usually reduces voice, respiratory, and general quality of life, and is sometimes life-threatening. Patients usually need repeated operations. The use of adjuvant bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A, has been described in several case reports, with a good efficacy and safety profile. METHODS: We report the cases of five patients with aggressive RRP who were treated with adjuvant systemic bevacizumab in a single Belgian tertiary center. RESULTS: A complete response was achieved in four patients after a median of 4.5 months, and a partial response in one. In all cases, the number of surgeries was drastically reduced, and quality of life improved. Toxicity was easily managed. CONCLUSIONS: Systemic bevacizumab seems to be an effective and safe adjuvant treatment for aggressive RRP.

The Efficacy of Human Papillomavirus Vaccination as an Adjuvant Therapy in Recurrent Respiratory Papillomatosis.

OBJECTIVE: To characterize the efficacy of human papillomavirus (HPV) vaccination as an adjuvant therapy in recurrent respiratory papillomatosis (RRP). DATA SOURCES: PubMed, Embase, Cochrane, Google Scholar, ClinicalTrials.gov, and Web of Science databases were queried for articles published before April 2021. REVIEW METHODS: All retrieved studies (n = 870) were independently analyzed by two reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement using predefined inclusion and exclusion criteria. 13 studies met inclusion criteria. A random-effects meta-analysis was performed to study intersurgical interval (ISI) and number of surgical procedures per year before and after vaccination. RESULTS: The systematic review included 13 studies, comprising 243 patients. All studies utilized the Gardasil® quadrivalent vaccine, and one study (Yiu et al. 2019) utilized both the quadrivalent and Gardasil® 9-valent vaccines. Our meta-analysis included 62 patients with ISI data across 4 studies, and 111 patients with data on the number of surgical procedures per month across 7 studies. The mean number of surgical procedures decreased by 4.43 per year after vaccination (95% CI, -7.48 to -1.37). Mean ISI increased after vaccination, with a mean difference of 15.73 months (95% CI, 1.46-29.99). Two studies reported on HPV sero-conversion, with HPV seropositivity of 100% prior to vaccination and 25.93% after vaccination. CONCLUSION: The addition of HPV vaccination was associated with an increase in time between surgeries and reduction in the number of surgical procedures required. HPV vaccination may be a beneficial adjuvant treatment for RRP. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2046-2054, 2023.

Surgical outcome of different surgical modalities for adult recurrent respiratory papillomatosis.

BACKGROUND: Surgical debulking remains the mainstay of treatment of adult-onset recurrent respiratory papillomatosis (AO-RRP). But there are no guidelines for decision-making of surgical modality. OBJECTIVES: This retrospective study aims to obtain a better understanding of AO-RRP, and select the best surgical modality for RRP among microdebrider, CO2 laser, and KTP laser. MATERIAL AND METHODS: Medical records of 72 AO-RRP patients were reviewed, with at least a 6-month follow-up. We focused on demographic data, the median treatment intervals (MTI) (Days), the survival curves, and treatment-related complications. RESULTS: Seventy-two AO-RRP and a total of 172 surgical procedures were included, with either the microdebrider (n = 46), CO2 laser (n = 102), or KTP laser (n = 24). The MTI of all patients was 230.0[132.0, 455.0] (median[P25-P75]), with microdebrider group (267.50[152.5, 449.5]), CO2 laser group (247.5[145.5, 474.7]), and KTP laser group (107.5[68.3, 330.5]), and there were no significant differences among three surgical modalities on MTI or survival curves (p > .05). The duration of surgery was 44.9[25.6] in the microdebriders group, 48.4 [29.5] in the CO2 laser group, and 51.3[18.4] in the KTP laser group, but there was no significant difference in the operation duration among the three groups (p > .05). Postoperative glottic webs and scar formations were found in 4.3% of patients in microdebrider group, 16.7% of patients in CO2 laser group, and 8.3% of patients in KTP group. CONCLUSION AND SIGNIFICANCE: Microdebrider surgery for RRP took the shortest time and had the lowest rate of postoperative complications. However, different surgical modalities are equally effective in controlling recurrence after RRP surgery.

Effect of Human Papillomavirus Subtype on the Rate of Positive Surgical Margin After Cervical Conization.

Objective. Human papillomavirus (HPV) infection is a risk factor for cervical carcinoma. Over 100 types of HPV have been identified. The excisional procedures are recommended for women with high-grade cervical intraepithelial neoplasia. Surgical margin status is an important predictor of the risk of relapse. The aim of the current study was to evaluate whether HPV genotype is a predictive factor of positive surgical margin after cervical cone excision. Materials and Methods. The records of 448 HPV-infected patients who underwent loop electrosurgical excision or cold knife conization at a tertiary gynecological cancer center were retrospectively reviewed. The patients were divided into 6 groups according to HPV positivity: HPV 16 only, HPV 18 only, HPV 16/18, other high-risk HPV (hrHPV), HPV 16/hrHPV, and HPV 18/hrHPV. Results. There was no significant difference between the HPV groups in terms of age, parity, menopausal status, endocervical canal involvement, conization method, and the rates of positive margin (P = .15, P = .49, P = .07, P = .20, P = .24, P = .39, respectively). Conclusion. The results show that HPV subtypes might not be associated with endocervical canal involvement and the rates of positive margin. In addition, margin status was not related to the conization method and the number of excised cervical tissue.