Population-based norms for the human papillomavirus-quality of life (HPV-QoL) questionnaire: A cross-sectional multicenter study.

INTRODUCTION: Human papillomavirus (HPV) diagnosis has a considerable emotional and psychological impact on women. To evaluate the impairment this infection leads to regarding quality of life (QoL), several scales have been suggested, such as the human-papillomavirus-quality-of-life (HPV-QoL) questionnaire. This has been validated for the Spanish population and measures the impact of HPV on health-related-quality-of-life (HR-QoL). However, normative values are yet to be developed. Thus, the objective was to describe the population-based norms of the HPV-QoL for Spanish women aged 25-65 years and to test the questionnaire's construct validity. MATERIAL AND METHODS: This was a cross-sectional nationwide multicenter study. Women from outpatient clinics in Spain aged 25-65 years, with a diagnosis of past or active HPV infection were recruited. The central tendency, dispersion, and percentiles were calculated for the total score and its dimensions for each age group. Construct validity was tested by analyzing age groups and their correlations with other related scales (12-Item General Health Questionnaire [GHQ-12], Female Sexual Function Index [FSFI], and Hospital Anxiety and Depression Scale [HADS]). RESULTS: A total of 1352 women were included in the study. The norms showed moderate and significant coefficients of correlation with other related scales. Significant differences between age strata groups were found according to educational level, sexual dysfunction, sexual activity, mental deterioration, and severity of anxiety and depression symptoms (p < 0.001 in all cases). The total score differed significantly between the groups (p = 0.006). Significant differences in the contagiousness, health, and sexuality dimensions (p < 0.05) were found among the groups. It was seen that HPV infection impaired women's QoL. Dimensions within all test age groups (p < 0.001 in all cases) were significantly different, with the health dimension being the highest contributor to women's QoL impairment, whereas social well-being was the main determinant of QoL. CONCLUSIONS: Population-based norms for the novel HPV-QoL questionnaire showed adequate validity and could be a useful tool for assessing the impact of QoL among women with HPV in Spain.

Risk factors for human papillomavirus infection and disease: A targeted literature summary.

Adolescents are the primary cohort for routine human papillomavirus (HPV) vaccination, but unvaccinated adults may also benefit. A lack of consensus on which adults to target and the presence of reimbursement barriers likely contribute to the lag in adult vaccinations, highlighting missed prevention opportunities. Understanding factors contributing to risk of HPV infection and disease could help in decision making on vaccination. This review summarizes existing literature on risk factors for HPV infection and disease and includes 153 studies reporting relative risks or odds ratios for factors associated with HPV infection or disease in adults, published between 2009 and 2020. Despite inconsistent design and reporting of risk factors across studies, this review confirmed several risk factors associated with adult infection, including human immunodeficiency virus positivity, number of sex partners, and smoking. These findings can support policymaking, guideline development, and clinical decision making for HPV vaccination and screening of high-risk adult groups.

Agreement on Lesion Presence and Location at Colposcopy.

OBJECTIVES/PURPOSE: The reproducibility and sensitivity of image-based colposcopy is low, but agreement on lesion presence and location remains to be explored. Here, we investigate the interobserver agreement on lesions on colposcopic images by evaluating and comparing marked lesions on digitized colposcopic images between colposcopists. METHODS: Five colposcopists reviewed images from 268 colposcopic examinations. Cases were selected based on histologic diagnosis, i.e., normal/cervical intraepithelial neoplasia (CIN)1 ( n = 50), CIN2 ( n = 50), CIN3 ( n = 100), adenocarcinoma in situ ( n = 53), and cancer ( n = 15). We obtained digitized time-series images every 7-10 seconds from before acetic acid application to 2 minutes after application. Colposcopists were instructed to digitally annotate all areas with acetowhitening or suspect of lesions. To estimate the agreement on lesion presence and location, we assessed the proportion of images with annotations and the proportion of images with overlapping annotated area by at least 4 (4+) colposcopists, respectively. RESULTS: We included images from 241 examinations (1 image from each) with adequate annotations. The proportion with a least 1 lesion annotated by 4+ colposcopists increased by severity of histologic diagnosis. Among the CIN3 cases, 84% had at least 1 lesion annotated by 4+ colposcopists, whereas 54% of normal/CIN1 cases had a lesion annotated. Notably, the proportion was 70% for adenocarcinoma in situ and 71% for cancer. Regarding lesion location, there was no linear association with severity of histologic diagnosis. CONCLUSION: Despite that 80% of the CIN2 and CIN3 cases were annotated by 4+ colposcopists, we did not find increasing agreement on lesion location with histology severity. This underlines the subjective nature of colposcopy.

Reproducible and clinically translatable deep neural networks for cervical screening.

Cervical cancer is a leading cause of cancer mortality, with approximately 90% of the 250,000 deaths per year occurring in low- and middle-income countries (LMIC). Secondary prevention with cervical screening involves detecting and treating precursor lesions; however, scaling screening efforts in LMIC has been hampered by infrastructure and cost constraints. Recent work has supported the development of an artificial intelligence (AI) pipeline on digital images of the cervix to achieve an accurate and reliable diagnosis of treatable precancerous lesions. In particular, WHO guidelines emphasize visual triage of women testing positive for human papillomavirus (HPV) as the primary screen, and AI could assist in this triage task. In this work, we implemented a comprehensive deep-learning model selection and optimization study on a large, collated, multi-geography, multi-institution, and multi-device dataset of 9462 women (17,013 images). We evaluated relative portability, repeatability, and classification performance. The top performing model, when combined with HPV type, achieved an area under the Receiver Operating Characteristics (ROC) curve (AUC) of 0.89 within our study population of interest, and a limited total extreme misclassification rate of 3.4%, on held-aside test sets. Our model also produced reliable and consistent predictions, achieving a strong quadratic weighted kappa (QWK) of 0.86 and a minimal %2-class disagreement (% 2-Cl. D.) of 0.69%, between image pairs across women. Our work is among the first efforts at designing a robust, repeatable, accurate and clinically translatable deep-learning model for cervical screening.

Steps to improve umbilical vein catheterization in neonatal care.

INTRODUCTION: In neonatal units, umbilical vessel catheterization is the preferred method to gain vascular access in the initial management of the newborn because it is quick and easy. The failure rate ranges from to 50%, as the catheter can be found in the portal system in up to 40% of cases, leading to complications. This failure rate warrants the investigation of different methods to reduce the frequency of catheter malposition. We describe different techniques to improve the success rate in umbilical vein catheterization, such as the double catheter technique, positioning the newborn in right lateral decubitus for insertion, liver compression, and ultrasound-guided catheter insertion. The primary objective of the study was to assess the impact of new techniques on the success rate of central umbilical venous catheterization. MATERIAL AND METHODS: Pre- and post-intervention quasi-experimental study in a level B NICU conducted in January-June 2022 (pre-intervention) and July-December 2022 (post-intervention). RESULTS: Prior to the introduction of these new catheterization techniques, the failure rate of blind umbilical catheter insertion was 52%. Since the introduction of these measures, the overall failure rate has decreased to 27%. CONCLUSIONS: After the introduction of the new catheterization and recanalization methods, our success rate in umbilical vein catheterization has increased, and we believe it is necessary to implement them in units with similar failure rates to ours.

Prophylactic HPV vaccines in patients with HPV-associated diseases and cancer.

Individuals with human papillomavirus (HPV)-related disease remain at risk for subsequent HPV infection and related disease after treatment of specific lesions. Prophylactic HPV vaccines have shown benefits in preventing subsequent HPV-related disease when administered before or soon after treatment. Based on our understanding of the HPV life cycle and vaccine mechanism of action, prophylactic HPV vaccination is not expected to clear active persistent HPV infection or unresected HPV-associated dysplastic tissue remaining after surgery. However, vaccination may reasonably be expected to prevent new HPV infections caused by a different HPV type as well as re-infection with the same HPV type, whether from a new exposure to an infected partner or through autoinoculation from an adjacent or distant productively infected site. In this review, we describe the evidence for using prophylactic HPV vaccines in patients with HPV-associated disease before, during, or after treatment and discuss potential mechanisms by which individuals with HPV-associated disease may or may not benefit from prophylactic vaccines. We also consider how precise terminology relating to the use of prophylactic vaccines in this population is critical to avoid the incorrect implication that prophylactic vaccines have direct therapeutic potential, which would be counter to the vaccine's mechanism of action, as well as considered off-label. In other words, the observed effects occur through the known mechanism of action of prophylactic HPV vaccines, namely by preventing virus of the same or a different HPV type from infecting the patient after the procedure.

[Isolation of Haemophilus no ducreyi in samples from the genital tract of men: Its clinical relationship]. / Aislamiento de Haemophilus no ducreyi en muestras del aparato genital de varones: relación con la clínica.

INTRODUCTION: With the advancement of microbiological methods, the isolation of less typical pathogens in cases of urethral and rectal infection is more frequent, apart from the classic etiological agents. One of them is formed by species of Haemophilus no ducreyi (HND). The objective of this work is to describe frequency, susceptibility to antibiotics, and clinical features of HDN urethritis and proctitis in adult males. PATIENTS AND METHODS: This is an observational retrospective descriptive study of the results obtained by the Microbiology laboratory of the Virgen de las Nieves University Hospital on the isolates of HND in genital and rectal samples from males between 2016 and 2019. RESULTS: HND was isolated in 135 (7%) of the genital infection episodes diagnosed in men. H. parainfluenzae was the most commonly isolated (34/45; 75.6%). The most frequent symptoms in men with proctitis were rectal tenesmus (31.6%) and lymphadenopathy (10.5%); in those with urethritis, dysuria (71.6%), urethral suppuration (46.7%) and gland lesions (27%), so differentiating it from infections caused by other genitopathogens is difficult. 43% of patients were HIV positive. Antibiotic resistance rates for H. parainfluenzae were high to quinolons, ampicillin, tetracycline and macrolides. CONCLUSION: HND species should be considered as possible etiologic agents in episodes of urethral and rectal infection in men, especially in cases with negative screening tests for agents that cause sexually transmitted infections (STIs). Its microbiological identification is essential for the establishment of an effective targeted treatment.

P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation.

p53 immunohistochemistry (IHC) has been proposed as a surrogate for TP53 mutations in penile squamous cell carcinomas (PSCC). We aimed to evaluate the performance of a pattern-based evaluation of p53 IHC in PSCC. Human papilloma virus (HPV) DNA testing, p16 and p53 IHC, and whole exome sequencing were performed in a series of 40 PSCC. p53 IHC was evaluated following a pattern-based framework and conventional p53 IHC evaluation. Out of 40 PSCC, 12 (30.0%) were HPV-associated, and 28 (70.0%) were HPV-independent. The agreement between the p53 IHC pattern-based evaluation and TP53 mutational status was almost perfect (k = 0.85). The sensitivity and accuracy of the pattern-based framework for identifying TP53 mutations were 95.5% and 92.5%, respectively, which were higher than the values of conventional p53 IHC interpretation (54.5% and 70.0%, respectively), whereas the specificity was the same (88.9%). In conclusions, the pattern-based framework improves the accuracy of detecting TP53 mutations in PSCC compared to the classical p53 IHC evaluation.

COVID-19-associated lung weakness (CALW): Systematic review and meta-analysis.

OBJECTIVES: To assess mortality and different clinical factors derived from the development of atraumatic pneumothorax (PNX) and/or pneumomediastinum (PNMD) in critically ill patients as a consequence of COVID-19-associated lung weakness (CALW). DESIGN: Systematic review with meta-analysis. SETTING: Intensive Care Unit (ICU). PARTICIPANTS: Original research evaluating patients, with or without the need for protective invasive mechanical ventilation (IMV), with a diagnosis of COVID-19, who developed atraumatic PNX or PNMD on admission or during hospital stay. INTERVENTIONS: Data of interest were obtained from each article and analyzed and assessed by the Newcastle-Ottawa Scale. The risk of the variables of interest was assessed with data derived from studies including patients who developed atraumatic PNX or PNMD. MAIN VARIABLES OF INTEREST: Mortality, mean ICU stay and mean PaO2/FiO2 at diagnosis. RESULTS: Information was collected from 12 longitudinal studies. Data from a total of 4901 patients were included in the meta-analysis. A total of 1629 patients had an episode of atraumatic PNX and 253 patients had an episode of atraumatic PNMD. Despite the finding of significantly strong associations, the great heterogeneity between studies implies that the interpretation of results should be made with caution. CONCLUSIONS: Mortality among COVID-19 patients was higher in those who developed atraumatic PNX and/or PNMD compared to those who did not. The mean PaO2/FiO2 index was lower in patients who developed atraumatic PNX and/or PNMD. We propose grouping these cases under the term COVID-19-associated lung weakness (CALW).

[COVID-19-associated lung weakness (CALW): Systematic review and meta-analysis]. / Debilidad pulmonar asociada a COVID-19 (DPAC): revisión sistemática y metaanálisis.

Objectives: To assess mortality and different clinical factors derived from the development of atraumatic pneumothorax (PNX) and/or pneumomediastinum (PNMD) in critically ill patients as a consequence of COVID-19-associated lung weakness (CALW). Design: Systematic review with meta-analysis. Setting: Intensive care unit (ICU). Participants: Original research evaluating patients, with or without the need for protective invasive mechanical ventilation (IMV), with a diagnosis of COVID-19 who had developed atraumatic PNX or PNMD on admission or during their hospital stay. Interventions: Data of interest were obtained from each article and analysed and assessed by the Newcastle-Ottawa Scale. The risk of the variables of interest was assessed by data derived from studies including patients who developed atraumatic PNX or PNMD. Main variables of interest: Mortality, mean ICU length of stay and mean PaO2/FiO2 at diagnosis. Results: Data were collected from 12 longitudinal studies. Data from a total of 4,901 patients were included in the meta-analysis. A total of 1,629 patients had an episode of atraumatic PNX and 253 patients had an episode of atraumatic PNMD. Despite finding significantly strong associations, the high heterogeneity between studies means that interpretation of the results should be made with caution. Conclusions: Mortality of COVID-19 patients was higher in those who developed atraumatic PNX and/or PNMD compared to those who did not. The mean PaO2/FiO2 index was lower in patients who developed atraumatic PNX and/or PNMD. We propose to group these cases under the term CAPD.

Human papillomavirus and p53 status define three types of vulvar squamous cell carcinomas with distinct clinical, pathological, and prognostic features.

INTRODUCTION: Based on their etiological relationship with human papillomavirus (HPV), the 2020 WHO classification has divided vulvar squamous cell carcinomas (VSCC) into two distinct types, HPV-associated and HPV-independent, and HPV-independent tumours have recently been divided according to p53 status. Nevertheless, the clinical and prognostic significance of this classification has not been clearly established. We analysed the differential clinical, pathological, and behavioural characteristics of these three types of VSCC in a large series of patients. METHODS AND RESULTS: VSCC samples from patients who underwent primary surgery at the Hospital Clinic of Barcelona, Spain, during a 47-year period (January 1975 to January 2022) were analysed (n = 190). HPV detection, p16, and p53 immunohistochemical staining were evaluated. We also analysed recurrence-free survival (RFS) and disease-specific survival (DSS). Thirty-three tumours (17.4%) were HPV-associated and 157 (82.6%) HPV-independent. Of these, 20 showed normal and 137 abnormal p53 expression. The two types of HPV-independent tumours showed worse RFS in the multivariate analysis (hazard ratio [HR] = 3.63; P = 0.023 for the HPV-independent p53 normal VSCC and HR = 2.78; P = 0.028 for the HPV-independent p53 abnormal VSCC). Although the differences were not significant, HPV-independent VSCC had worse DSS than HPV-associated VSCC. Although patients with HPV-independent p53 normal tumours had worse RFS than patients with HPV-independent p53 abnormal tumours, the DSS was better for the former group. Only advanced FIGO stage was associated with worse DSS in multivariate analysis (HR = 2.83; P = 0.010). CONCLUSION: The association of HPV and p53 status have prognostic implications, reinforcing a three-tier molecular classification of VSCC (HPV-associated VSCC, HPV-independent VSCC with normal p53, HPV-independent VSCC with abnormal p53).

REPRODUCIBLE AND CLINICALLY TRANSLATABLE DEEP NEURAL NETWORKS FOR CANCER SCREENING.

Cervical cancer is a leading cause of cancer mortality, with approximately 90% of the 250,000 deaths per year occurring in low- and middle-income countries (LMIC). Secondary prevention with cervical screening involves detecting and treating precursor lesions; however, scaling screening efforts in LMIC has been hampered by infrastructure and cost constraints. Recent work has supported the development of an artificial intelligence (AI) pipeline on digital images of the cervix to achieve an accurate and reliable diagnosis of treatable precancerous lesions. In particular, WHO guidelines emphasize visual triage of women testing positive for human papillomavirus (HPV) as the primary screen, and AI could assist in this triage task. Published AI reports have exhibited overfitting, lack of portability, and unrealistic, near-perfect performance estimates. To surmount recognized issues, we implemented a comprehensive deep-learning model selection and optimization study on a large, collated, multi-institutional dataset of 9,462 women (17,013 images). We evaluated relative portability, repeatability, and classification performance. The top performing model, when combined with HPV type, achieved an area under the Receiver Operating Characteristics (ROC) curve (AUC) of 0.89 within our study population of interest, and a limited total extreme misclassification rate of 3.4%, on held-aside test sets. Our work is among the first efforts at designing a robust, repeatable, accurate and clinically translatable deep-learning model for cervical screening.

Vulvar squamous cell carcinoma arising on human papillomavirus-independent precursors mimicking high-grade squamous intra-epithelial lesion: a distinct and highly recurrent subtype of vulvar cancer.

AIMS: Each category of vulvar squamous cell carcinoma (VSCC), human papillomavirus (HPV)-associated and HPV-independent, arises on a specific intra-epithelial precursor: high-grade squamous intra-epithelial lesions (HSIL) and differentiated vulvar intra-epithelial neoplasia (dVIN), respectively. However, a subset of HPV-independent VSCC arises on an intra-epithelial precursor closely mimicking HSIL. We aimed to explore the clinicopathological features of the HPV-independent tumours with HSIL-like lesions and compare them with HPV-independent VSCC with dVIN and HPV-associated tumours with HSIL. METHODS AND RESULTS: We retrospectively identified 105 cases of surgically treated VSCC with adjacent intra-epithelial precursors. The cases were classified into three groups based on the HPV status and the adjacent precursor identified: (i) HPV-associated VSCC with HSIL (n = 26), (ii) HPV-independent VSCC with dVIN lesions (n = 54) and (iii) HPV-independent VSCC with HSIL-like lesions (n = 25). We analysed the histological and clinical features including the recurrence-free survival and disease-specific survival in the three groups. Patients with HPV-independent VSCC with HSIL-like lesions and with dVIN were older than patients with HPV-associated VSCC (76 and 77 versus 66 years, respectively, P < 0.001). HPV-independent VSCC with HSIL-like lesions recurred more frequently [hazard ratio (HR) = 3.87; P < 0.001] than HPV-independent VSCC with dVIN (HR = 2.27; P = 0.1) and HPV-associated VSCC (HR = 1). In the multivariate analysis, HPV-independent VSCC with HSIL-like lesions remained significant for recurrence. No differences in disease-specific survival were observed between the three groups. CONCLUSIONS: Even though VSCC with HSIL-like lesions are not associated with higher mortality, they are more likely to recur and might benefit from more intensive treatment strategies and closer surveillance after treatment.

Predictive factors of preoperative sentinel lymph node detection in intermediate and high-risk endometrial cancer.

BACKGROUND: In endometrial cancer (EC), sentinel lymph node (SLN) mapping has emerged as an alternative to systematic lymphadenectomy. Little is known about factors that might influence SLN preoperative detection. The aim of our study was to evaluate the clinical and technical variables that may influence on the success of SLN detection in preoperative lymphatic mapping in patients with intermediate and high-risk EC when performing transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR). METHODS: Between March 2006 and March 2017, we prospectively enrolled patients with histologically confirmed EC with intermediate or high-risk of lymphatic involvement. All women underwent SLN detection by using TUMIR approach. After radiotracer injection, pelvic and abdominal planar and SPECT/CT images were acquired to obtain a preoperative lymphoscintigraphic mapping. Pattern of drainage was registered and analyzed to identify the factors directly involved in drainage. Sonographer learning curves to perform TUMIR approach were created following Cumulative Sum and Wright methods. Univariate and multivariate analyses were performed using logistic regression. RESULTS: During study period, 123 patients were included. SLN preoperative detection rate was 70.7%. Age under 75 years at diagnosis (P<0.01), radiotracer injection above 4 mL -high-volume- (P<0.01), and tumoral size below 2 cm (P=0.04) were associated with higher SLN preoperative detection rate. Twenty-five procedures were necessary to attain an adequate performance in TUMIR approach. CONCLUSIONS: The higher SLN preoperative detection rate in women with intermediate and high-risk endometrial cancer after TUMIR approach was related with younger age, smaller tumors and high-volume injection of radiotracer. Sonographers are required to perform 25 procedures before acquiring an expertise in radiotracer injection.

FAM19A4/miR124-2 Methylation Testing and Human Papillomavirus (HPV) 16/18 Genotyping in HPV-Positive Women Under the Age of 30 Years.

BACKGROUND: High-grade squamous intraepithelial lesions (HSIL) or cervical intraepithelial neoplasia (CIN) grade 2/3 lesions in human papillomavirus (HPV)-positive women <30 years of age have high spontaneous regression rates. To reduce overtreatment, biomarkers are needed to delineate advanced CIN lesions that require treatment. We analyzed the FAM19A4/miR124-2 methylation test and HPV16/18 genotyping in HPV-positive women aged <30 years, aiming to identify CIN2/3 lesions in need of treatment. METHODS: A European multicenter retrospective study was designed evaluating the FAM19A4/miR124-2 methylation test and HPV16/18 genotyping in cervical scrapes of 1061 HPV-positive women aged 15-29 years (690 ≤CIN1, 166 CIN2, and 205 CIN3+). A subset of 62 CIN2 and 103 CIN3 were immunohistochemically characterized by HPV E4 expression, a marker for a productive HPV infection, and p16ink4a and Ki-67, markers indicative for a transforming infection. CIN2/3 lesions with low HPV E4 expression and high p16ink4a/Ki-67 expression were considered as nonproductive, transforming CIN, compatible with advanced CIN2/3 lesions in need of treatment. RESULTS: FAM19A4/miR124-2 methylation positivity increased significantly with CIN grade and age groups (<25, 25-29, and ≥30 years), while HPV16/18 positivity was comparable across age groups. FAM19A4/miR124-2 methylation positivity was HPV type independent. Methylation-positive CIN2/3 lesions had higher p16ink4a/Ki-67-immunoscores (P = .003) and expressed less HPV E4 (P = .033) compared with methylation-negative CIN2/3 lesions. These differences in HPV E4 and p16ink4a/Ki-67 expression were not found between HPV16/18-positive and non-16/18 HPV-positive lesions. CONCLUSIONS: Compared with HPV16/18 genotyping, the FAM19A4/miR124-2 methylation test detects nonproductive, transforming CIN2/3 lesions with high specificity in women aged <30 years, providing clinicians supportive information about the need for treatment of CIN2/3 in young HPV-positive women.

Clinical significance of isolation of Haemophilus no ducreyi in genital samples. Systematic review.

INTRODUCTION AND OBJECTIVES: Currently, the microbiological diagnosis of genital infections is carried out with molecular methods, which allow the detection of less frequent etiological agents but with potential pathogenic importance, such as Haemophilus spp. The objective of this review is to analyse and highlight the clinical importance of the isolation of Haemophilus spp. in genital and rectal infections, excluding Haemophilus ducreyi. MATERIAL AND METHODS: A systematic review was carried out based on an exhaustive search of the publications included in the MEDLINE database up to August 5, 2021, on the presence of Haemophilus spp. in genital and rectal infections, excluding H. ducreyi. RESULTS: After reviewing what was described in the literature, Haemophilus spp. (excluding H. ducreyi: HSNOD) was detected in 2397 episodes of genital infection, the most frequently isolated species being H. influenzae and H. parainfluenzae. Most of the episodes (87,6%) are constituted by single isolation. There is a slight predominance in women (48,3%) where it can cause vaginitis, salpingitis, endometritis or complications during pregnancy. In men, the clinical picture usually corresponds to urethritis. Most of the samples correspond to vaginal and urethral exudates, with a minority representation at the rectal level (2.3%). CONCLUSION: HSNOD plays a relevant pathogenic role in episodes of genital infection, so microbiological diagnostic protocols must include methods that allow their detection, as well as include them in the etiological spectrum of this type of clinical picture.

Differential etiopathogenic features of vulvar squamous cell carcinomas in sub-Saharan Africa and Europe.

Two pathways have been described for vulvar squamous cell carcinomas (VSCC), one associated with human papillomavirus (HPV), and the other HPV-independent. We compared the etiopathogenic features of a series of VSCC from Mozambique, a sub-Saharan country with high prevalence of HPV and HIV, with those of Spain, a European country with low prevalence of HPV and HIV. All VSCC diagnosed at the two institutions from January 2018 to December 2020 were included (n = 35 and n = 41, respectively). HPV DNA detection and genotyping, and immunohistochemistry for p16 and p53 were performed. Tumors showing p16 positive staining and/or HPV DNA positivity were considered HPV-associated. 34/35 tumors (97%) from Mozambique and 8/41 (19%) from Spain were HPV-associated (P < .001). Mean age of the patients from Mozambique and Spain was 45 ± 12 and 72 ± 14, respectively (P < .001). No differences were found in terms of HPV genotypes or multiple HPV infection rates. 1/35 tumors (3%) from Mozambique and 29/41 (70%) from Spain showed abnormal p53 immunostaining (P < .001). In contrast with the predominance of HPV-independent VSCC affecting old women in Europe, most VSCC in sub-Saharan Africa are HPV-associated and arise in young women. This data may have important consequences for primary prevention of VSCC worldwide.

Penile Squamous Cell Carcinomas in Sub-Saharan Africa and Europe: Differential Etiopathogenesis.

Penile squamous cell carcinomas (PSCC) are classified by the World Health Organization into two categories based on their relationship with the human papillomavirus (HPV): HPV-associated and HPV-independent. We compared a cohort of PSCC from Mozambique, a sub-Saharan country in southeast Africa with a high prevalence of HPV and HIV infection, and Spain, a country in southwestern Europe with a low prevalence of HPV and HIV, to study the distribution of the etiopathogenic categories of these tumors in both sites. A total of 79 PSCC were included in the study (28 from Mozambique and 51 from Spain). All cases underwent HPV-DNA polymerase chain reaction (PCR) testing, genotyping, and immunohistochemistry for p16 and p53. Any PSCC showing either p16 overexpression or HPV-DNA in PCR analysis was considered HPV-associated. Overall, 40/79 (50.6%) tumors were classified as HPV-associated and 39 (49.4%) as HPV-independent. The two sites showed marked differences: 25/28 (89.3%) tumors from Mozambique and only 15/51 (29.4%) from Spain were HPV-associated (p < 0.001). HPV16 was the most frequent HPV type identified in 64.0% (16/25) of the HPV-associated tumors from Mozambique, and 60.0% (9/15) from Spain (p = 0.8). On average, patients from Mozambique were almost two decades younger than those from Spain (mean age 50.9 ± 14.9 and 69.2 ± 13.3, respectively [p < 0.001]). In conclusion, significant etiopathogenic differences between PSCC in Mozambique and Spain were observed, with a remarkably high prevalence of HPV-associated tumors in Mozambique and a relatively low prevalence in Spain. These data may have important consequences for primary prevention of PSCC worldwide.

Comparison of accuracy and reproducibility of colposcopic impression based on a single image versus a two-minute time series of colposcopic images.

OBJECTIVE: Colposcopy is an important part of cervical screening/management programs. Colposcopic appearance is often classified, for teaching and telemedicine, based on static images that do not reveal the dynamics of acetowhitening. We compared the accuracy and reproducibility of colposcopic impression based on a single image at one minute after application of acetic acid versus a time-series of 17 sequential images over two minutes. METHODS: Approximately 5000 colposcopic examinations conducted with the DYSIS colposcopic system were divided into 10 random sets, each assigned to a separate expert colposcopist. Colposcopists first classified single two-dimensional images at one minute and then a time-series of 17 sequential images as 'normal,' 'indeterminate,' 'high grade,' or 'cancer'. Ratings were compared to histologic diagnoses. Additionally, 5 colposcopists reviewed a subset of 200 single images and 200 time series to estimate intra- and inter-rater reliability. RESULTS: Of 4640 patients with adequate images, only 24.4% were correctly categorized by single image visual assessment (11% of 64 cancers; 31% of 605 CIN3; 22.4% of 558 CIN2; 23.9% of 3412 < CIN2). Individual colposcopist accuracy was low; Youden indices (sensitivity plus specificity minus one) ranged from 0.07 to 0.24. Use of the time-series increased the proportion of images classified as normal, regardless of histology. Intra-rater reliability was substantial (weighted kappa = 0.64); inter-rater reliability was fair ( weighted kappa = 0.26). CONCLUSION: Substantial variation exists in visual assessment of colposcopic images, even when a 17-image time series showing the two-minute process of acetowhitening is presented. We are currently evaluating whether deep-learning image evaluation can assist classification.

HPV Vaccination in Women with Cervical Intraepithelial Neoplasia Undergoing Excisional Treatment: Insights into Unsolved Questions.

Several questions regarding the role of vaccination in women treated for high-grade cervical intraepithelial lesion (HSIL) have not been clarified. One of the main queries is whether the time at which the vaccine is administered (before or after treatment) influences the protection against post-treatment HSIL. A second unanswered question is whether the vaccine has any effect in women with persistent HPV after treatment. We aimed to address these questions in a study of 398 women undergoing excisional treatment from July 2016 to December 2019. Vaccination was funded and offered to all women undergoing treatment. A total of 306 women (76.9%) accepted HPV vaccination (vaccinated group): 113 (36.9%) received the first dose before excision and 193 (63.1%) after the procedure. A total of 92 women (23.1%) refused the vaccine (non-vaccinated group). Women vaccinated before treatment showed a lower rate of post-treatment HSIL compared with non-vaccinated women (0.9% vs. 6.5%; p = 0.047). Among women with persistent HPV infection after treatment, those who had received the vaccine showed a lower prevalence of post-treatment HSIL than non-vaccinated women (2.6% vs. 10.5%; p = 0.043). In conclusion, this study shows that HPV vaccination before treatment reduces the prevalence of post-treatment HSIL and suggests that vaccination might even benefit women with persistent HPV after treatment.