Diffuse Thyroid Lipomatosis and Amyloid Goiter With Incidental Papillary Thyroid Carcinoma: A Rare Case Report.

Lipoid lesions of the thyroid gland are very rare. Fat-containing thyroid lesions include a variety of clinical-pathological disorders, such as adenolipomas, thyrolipomatosis, and lipomatous tissue, in the event of amyloidosis. Herein, we report a case of diffuse thyrolipomatosis with amyloidosis and incidentally detected papillary carcinoma of the thyroid in a 51-year-old female patient who clinically presented with a multinodular goiter. Amyloidosis in papillary carcinoma of the thyroid is very rare and can be primary or secondary amyloidosis. Thyrolipomatosis, amyloid goiter, and papillary carcinoma of the thyroid is a rare combination, and to our knowledge, this is the third reported case in the literature. The association of amyloidosis and the rare occurrence of a differentiated carcinoma have to be considered, as in the case of thyroid lipomatosis.

Interobserver agreement in the interpretation of anal cytology.

BACKGROUND: Anal cytology represents a tool for anal cancer screening in high-risk populations. In addition to accuracy, the reproducibility of the interpretation is of key importance. The authors evaluated the agreement of anal cytologic interpretation between two cytopathologists. METHODS: Liquid-based cytologic slides from human immunodeficiency virus (HIV)-negative men who have sex with men (MSM) were evaluated by two readers with at least 10 years of expertise in cervical cytology. Cases with a discordant interpretation were reviewed, and a consensus was reached. Human papillomavirus (HPV) genotyping was performed using a proprietary HPV genotyping test. Unweighted and weighted Cohen kappa and 95% confidence interval (CI) values were calculated. RESULTS: Overall, 713 slides that were adequate for interpretation were evaluated (MSM: median age, 33 years). An HPV test was performed on 620 samples (87.0%). Considering a dichotomous interpretation (negative for intraepithelial lesion or malignancy vs. atypical squamous cells of undetermined significance or worse), the crude agreement between the two readers was 93.3% (kappa = 0.82; 95% CI, 0.77-0.87). Once a consensus for discordant cases was reached, the best agreement was found for the negative for intraepithelial lesion or malignancy category (511 of 528 samples; 96.8%), whereas the atypical squamous cells of undetermined significance category showed the lowest agreement (90 of 117 samples, 76.9%). Considering the individual cytologic categories, overall agreement was 92.1% (kappa = 0.85; 95% CI, 0.81-0.89). The discordant interpretations were not associated with high-risk HPV infection, HPV16 infection, or MSM age. CONCLUSIONS: The results indicating excellent interobserver agreement in this study substantiate the use of anal cytology in the setting of human immunodeficiency virus-negative MSM.

Metabolic syndrome in patients with type 1 diabetes mellitus at a tertiary centre in North India: A five year follow up study.

BACKGROUND AND AIMS: Metabolic syndrome (MS) is prevalent in the Indian population and has been traditionally linked to Type 2 diabetes mellitus (T2DM). Its presence is now being increasingly recognized in patients with Type 1 diabetes mellitus (T1DM). Presence of MS may increase the risk of diabetes related complications. This study was designed to determine the prevalence of MS in a cohort of patients with T1DM at baseline and at 5 years of follow up. METHODS: Longitudinal cohort study in a tertiary care center in North India. Patients with T1DM attending the Diabetes of the Young (DOY) Clinic from January 2015 to March 2016 included. Microvascular and macrovascular complications assessed. The cohort was followed after a period of 5 years. RESULTS: We included 161 patients (males, 49.4%) with a median (IQR) age of 23 (18-34) years and median (IQR) diabetes duration of 12 (7, 17) years. At baseline, 31 (19.2%) patients had MS. Patients with MS were more likely to have microvascular complications: retinopathy (p = 0.003), neuropathy (p = 0.02) and nephropathy (p = 0.04). Independent predictors of MS: insulin sensitivity (IS) (adjusted OR (aOR) 0.02 [95% CI, 0.003-0.118]), body weight (aOR 1.05 [95% CI, 1.007-1.108]), diastolic blood pressure (aOR 1.08 [95% CI, 1.01-1.15]) and duration of diabetes (aOR 1.09 [95% CI, 1.02-1.16]). On follow-up (n = 100), 13 (13%) had MS. CONCLUSIONS: One in 5 patients with T1DM suffers from MS, and is therefore predisposed to its attendant risks, calling for early identification and targeted interventions.

Alpha, Beta, and Gamma Human Papillomaviruses in Genital Lichen Sclerosus: A Retrospective Cross-Sectional Study.

BACKGROUND: Lichen sclerosus (LS) is an inflammatory disease mostly arising at the genital level. It is unclear whether human papillomaviruses (HPVs) have an etiological significance in LS, and data on their prevalence in patients with LS are controversial. OBJECTIVES: The authors assessed alpha, beta, and gamma HPV prevalence in patients with genital LS. The association of HPV positivity with demographic and clinical factors was also investigated. METHODS: One hundred thirty-two formalin-fixed, paraffin-embedded LS samples (2016-2020) were retrieved from the archives of a pathology department. Alpha HPVs were genotyped with the INNO-LiPA HPV Genotyping Extra II kit. Beta and gamma HPVs were searched by multiplex Polymerase Chain Reaction. Immunostaining for p16 INK4a was performed on high-risk HPV-positive samples. RESULTS: Patients had a median age of 61 years, were mostly women ( n = 73, 55.3%), and with an early disease stage ( n = 79, 59.8%). Alpha HPVs were detected in 12/132 cases (9.1%). Among the 5 high-risk HPV-positive cases, only 2 displayed a strong and diffuse p16 INK4a staining. Beta genus was the most prevalent (35/132, 26.5%) and HPV5 was the most frequent beta genotype (25/132, 18.9%). There were 3 gamma HPV-positive cases among those with a valid result (3/131, 2.3%). Multiple infections with genotypes belonging to different genera were infrequent (3/131, 2.3%). No significant differences in the prevalence of the individual genera were observed according to sex and disease stage. CONCLUSIONS: Of the 3 HPV genera, beta genus showed the highest prevalence. Further research is needed to clarify whether the presence of beta HPVs in genital LS has a clinical significance.

Incidence of abnormal anal cytology in HIV-infected and HIV-uninfected men who have sex with men.

INTRODUCTION: Anal cytology is used in the prevention of anal cancer, which disproportionally affects men who have sex with men (MSM). Data on the incidence of cytologic abnormalities in these individuals are scant. METHODS: MSM with baseline negative anal cytology and at least one further adequate cytology were included. Incidence rate for positive atypical squamous cells of undetermined significance (ASC-US+) was calculated. Kaplan-Meier curves were compared by log-rank test according to HIV status, baseline high-risk human papillomavirus (HPV) (high-risk HPV-negative, HPV16-positive, other high-risk HPV-positive [non-HPV16]) and high-risk HPV persistence (positive from baseline to the first ASC-US+ or last visit for those who remained cytologically negative). Cox univariate and multivariate analyses were performed. RESULTS: A total of 250 MSM were included: 52/153 (34.0%) HIV-uninfected MSM had an ASC-US+ report at follow-up (incidence: 13.1 × 100 person-years; 95% CI, 9.8-17.2); 48/97 (49.5%) HIV-infected MSM developed cytologic abnormalities (incidence: 16.0 × 100 person-years; 95% CI, 11.8-21.2). ASC-US+ incidence in HIV-uninfected and HIV-infected MSM did not differ significantly (p = .32). Kaplan-Meier curves did not differ significantly according to baseline high-risk HPV. Differences were significant between those with and without persistent high-risk HPVs, both among HIV-uninfected (p = .03) and HIV-infected MSM (p = .008). Age (adjusted hazard ratio [aHR], 0.98; 95% CI, 0.96-0.99), high-risk HPV persistence (aHR, 1.57; 95% CI, 1.02-2.39), and condomless receptive anal sex (aHR, 1.99; 95% CI, 1.31-3.03) were predictors for incident ASC-US+. CONCLUSIONS: Despite the limited number of subjects, in our study HIV-uninfected and HIV-infected MSM have a similar ASC-US+ incidence. Occurrence of ASC-US+ was significantly affected by age, high-risk HPV persistence, and condomless receptive anal sex. The assessment of HPV persistence might identify those MSM at higher risk for anal lesions.

Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

Prevalence of 13 polyomaviruses in actinic keratosis and matched healthy skin samples of immunocompetent individuals.

BACKGROUND: Actinic keratosis (AK) is a precursor of cutaneous squamous cell carcinoma (cSCC). UV radiation is the major risk factor for AK, but certain human papillomaviruses (HPVs) of the beta genus are also involved in its development. Differently, the role of polyomaviruses (PyVs) in skin carcinogenesis is still debated. Fiftheen PyVs have been isolated from human tissues so far, including Merkel cell polyomavirus (MCPyV), the aetiological agent of Merkel cell carcinoma. METHODS: The presence of 13 PyVs was assessed in skin samples from AK patients (n = 342). Matched fresh-frozen scrapings from healthy skin (HS) and AK lesions from 242 patients, and formalin-fixed paraffin-embedded AK biopsies from a different cohort of 100 patients were analyzed by multiplex PyVs genotyping assay. RESULTS: The most frequent lesion site was the scalp in men (27.3%), and the cheek area in women (29.0%). Differences between men and women were significant for the scalp, the cheek area and the lips. Almost all the scrapings were PyV-positive (HS: 89.7%, AK: 94.6%; p = 0.04). The three most frequent PyVs were MCPyV, HPyV6 and JCPyV (HS: 87.2%, 58.7%, 6.6%, respectively; AK: 88.8%, 51.2%, 9.9%, respectively). HPyV9, TSPyV, BKPyV, HPyV7, LIPyV and SV40 were detected in < 2% of the scrapings. In most cases, matched HS and AK scrapings were both positive (MCPyV: 78.1%, HPyV6: 41.7%), or both negative for the individual genotypes (for the remaining PyVs). PyV prevalence in AK biopsies was 22.0%. Only MCPyV (21.0%) and HPyV6 (3.0%) were detected in these samples. CONCLUSIONS: PyV prevalence in HS and AK scrapings was high, but detection of PyVs exclusively in AK scrapings was rare. PyV positivity rate in AK biopsies was modest. Further research is need to reach firm conclusions regarding the role of these viruses in AK development.

Pharyngocutaneous Fistula Following Primary and Salvage Laryngectomy: Aetiology and Predictive Factors.

Laryngeal cancer treatment is often wrought with challenges, pharyngocutaneous fistula formation (PCF) in patients undergoing either primary or salvage laryngectomy for laryngeal and hypopharyngeal for squamous cell carcinoma is an important one. We aimed to study the factors before and at the surgery that are associated with PCF formation in a South Indian tertiary care hospital. A retrospective chart review of 127 patients who underwent total laryngectomy (TL) between May 2014 and April 2019 at our centre were done. Data was collected, including patient age and gender, comorbidities (Diabetes mellitus, COPD and hypothyroidism), smoking, tumor stage and site, prior tracheostomy, prior radiation, concurrent neck dissection and type of pharyngoplasty, Preoperative hemoglobin and albumin levels, surgical margin status and development of a PCF was also done. Further details specific to the development of a PCF were recorded for that subset of patients including the length of time to fistula, mode of closure, time of closure and modality of management. The overall incidence of PCF was 16.5% (21 of 127 patients), and the median time from TL to the diagnosis of PCF was 6 days (range, 3-20 days). The analysis was done separately for laryngectomies without any pharyngeal reconstruction (112/127 patients). In patients treated with a primary TL, the incidence of PCF was 12.20% (10 of 82) and 26.66% (8 of 30) after salvage TL. Subset analysis for type of pharyngoplasty repair showed 12% (15/127) underwent different types of vascularised/muscular flap for smaller residual pharyngeal mucosa, of which 20% (3/15) developed PCF and one patient developed haematoma needing exploration and re-suturing. The predictive factors for PCF were hypopharynx cancer (P < 0.05), surgical margin positivity (P < 0.0001), female gender (P < 0.05), absence of prior tracheostomy (P < 0.05) and tumor extension into pyriform sinus mucosa (P < 0.05). Preoperative patient factors of gender and site of primary along with histological margin positivity and extension of tumor to the pyriform sinus mucosa were significant risk factors for PCF formation. Pre-Op radiotherapy remains a strong clinical suspicion but not statistically significant.

Immunogenicity and Safety of BNT162b2 Homologous Booster Vaccination in People Living with HIV under Effective cART.

Data on COVID-19 boosting vaccination in people living with HIV (PLWH) are scant. We investigated the immunogenicity and safety of the BNT162b2 homologous boosting vaccination. Anti-SARS-CoV-2 spike antibodies (LIAISON® SARS-CoV-2 S1/S2 IgG test, DiaSorin®), CD4+, CD8+ and viraemia were monitored at T0 (pre-vaccination), T1 (4 weeks after the second dose), T2 (pre-booster) and T3 (4 weeks after the booster dose). Humoral responses were evaluated according to sex, age, BMI, nadir and baseline CD4+ counts, as well as type of cART regimen. Forty-two subjects were included: the median age was 53 years (IQR: 48−61); the median time since HIV was 12.4 years (IQR: 6.5−18.3); the median nadir and baseline CD4+ counts were 165 (IQR: 104−291) and 687 cells/mm3 (IQR: 488−929), respectively. The booster dose was administered at a median of 5.5 months after the second dose. Median anti-SARS-CoV-2 IgG concentration had significantly decreased at T2 compared to T1 (107 vs. 377, p < 0.0001). Antibody levels elicited by the booster dose (median: 1580 AU/mL) were significantly higher compared with those of all the other time points (p < 0.0001). None of the investigated variables significantly affected antibody response induced by the booster dose. Local and systemic side-effects were referred by 23.8% and 14.3% of the subjects, respectively. One patient developed sensorineural hearing loss (SNHL) 24 h after boosting. He recovered auditory function upon endothympanic administration of corticosteroids. The BNT162b2 boosting vaccination in PLWH is safe and greatly increased the immune response with respect to the primary vaccination.

Incidence and clearance of anal high-risk Human Papillomavirus infection and their risk factors in men who have sex with men living with HIV.

HIV-infected men who have sex with men (MSM) display the highest prevalence of anal infection by high-risk Human Papillomaviruses (hrHPVs) and incidence of anal carcinoma. Anal specimens were genotyped by the Linear Array. Incidence and clearance of anal infection by hrHPVs, hrHPVs other than HPV16, low-risk HPVs, and four individual types (6,11,16,18) were estimated using a two-state Markov model. Determinants for incidence and clearance were assessed by logistic regression. Overall, 204 individuals were included (median age 42 years, IQR = 34-49). For hrHPVs, incidence and clearance rates were 36.1 × 1000 person-months (p-m) (95% CI 23.3-56.5) and 15.6 × 1000 p-m (95% CI 10.7-23.3), respectively. HPV16 showed a higher incidence than HPV18 (10.2 vs. 7.2 × 1000 p-m). Its clearance was more than twofold lower than that of HPV18 (30.1 vs. 78.2 × 1000 p-m). MSM receiving cART displayed a 68% to 88% decrease in risk of acquiring hrHPVs, hrHPVs other than HPV16, HPV16, and HPV18 (adjusted Hazard Ratio [aHR] 0.13, 95% CI 0.02-0.67; aHR 0.22, 95% CI 0.06-0.78; aHR 0.32, 95% CI 0.12-0.90; aHR 0.12, 95% CI 0.04-0.31, respectively) than patients not treated. A nadir CD4 + count < 200 cells/mm3 significantly reduced the clearance of hrHPVs other than HPV16 (aHR 0.39, 95% CI 0.17-0.90). cART use reduces the risk of acquiring anal infection by hrHPVs.

Online Health Information Seeking Behaviour Due to COVID-19 Pandemic-Induced Health Related Anxiety among the General Population in India.

BACKGROUND: Persons with anxiety regarding health may have an increased tendency to seek online health information especially during a pandemic. The primary objective of this study was to determine COVID-19 induced health anxiety among the general population in India using Google Trends data. METHODS: Online health information seeking behaviour with respect to high-risk comorbid conditions for severe COVID-19 disease during the pandemic period was compared to that of the previous year. Correlation between the COVID-19 incidence and online health information seeking behaviour was also computed to explore if the observed health anxiety was due to the pandemic. RESULTS: Overall, the online health information seeking behaviour was highest for diabetes both during (81.46±8.84) and before the pandemic (64.47±9.48). A significant increase (p<0.001) in the information seeking behaviour during the pandemic was observed with all the four high-risk comorbid conditions including diabetes (+16.99), hypertension (+22.57), lung disease (+21.79), and cardiovascular disease (+14.08). The behaviour with respect to diabetes (r=0.39), hypertension (r=0.48) and lung disease (r=0.69) showed significant positive correlation with the COVID-19 incidence. The observed health anxiety was regardless of prevalence, urbanization and literacy rates of individual states. CONCLUSIONS: The general population in India has increased its online health information seeking behaviour during the pandemic and this may be due to an underlying health anxiety due to COVID-19.

Cell-Free Human Papillomavirus-DNA for Monitoring Treatment Response of Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.

OBJECTIVES/HYPOTHESIS: The aim of this study was to assess the value of cell-free human papillomavirus-DNA (cfHPV-DNA) as a diagnostic test for the post-treatment surveillance of patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) through a systematic review and meta-analysis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A literature search was conducted in three databases (MEDLINE, Embase, and Scopus) in January 2021. The population included patients with HPV-positive HNSCC. The intervention was the use of the repeated liquid biopsy with circulating HPV-DNA detection during follow-up. The outcome was to establish the value of cfHPV-DNA as a diagnostic test for the post-treatment surveillance of patients with HPV-positive HNSCC. RESULTS: Ten studies included in the meta-analysis provided a total of 457 patients with HPV-positive HNSCC. The meta-analytic study estimated the diagnostic performance of cfHPV-DNA as follows: pooled sensitivity and specificity of 0.65 (95% confidence interval [CI]: 0.40-0.84) and 0.99 (99% CI: 0.96-0.99), respectively; positive and negative likelihood ratios of 62.5 (99% CI: 22.9-170.2) and 0.05 (99% CI: 0.013-0.24), respectively; and pooled diagnostic odds ratio of 371.66 (99% CI: 60.4-2286.7). CONCLUSION: Currently, the follow-up protocol for HNSCC patients includes routine clinical evaluation and radiological imaging. Biomarkers to monitor this disease are not established. Considering its high specificity, cfHPV-DNA represents a potential confirmatory test in the case of positive positron emission tomography and computed tomography. In the near future, cfHPV-DNA could be used as a biomarker for monitoring the treatment response during the clinical trials of de-escalation therapy or immunotherapy. Larger sample sizes and the homologation of study protocols and methodology are needed to better establish its utility in the clinical practice. Laryngoscope, 132:560-568, 2022.

Human Papillomavirus Oral Infection: Review of Methodological Aspects and Epidemiology.

Oral infection by Human Papillomavirus (HPV) has recently gained great attention because of its involvement in the development of a subset of head and neck squamous cell carcinoma. The role of specific Alpha-HPVs in this regard has been well established, whereas the contribution of other genera is under investigation. Despite their traditional classification as "cutaneous" types, Beta and Gamma HPVs are frequently detected in oral samples. Due to the lack of a standardized protocol, a large variety of methodologies have been used for oral sample collection, DNA extraction, HPV detection and genotyping. Laboratory procedures influence the evaluation of oral HPV prevalence, which largely varies also according to the population characteristics, e.g., age, gender, sexual behavior, Human Immunodeficiency Virus (HIV) status. Nevertheless, oral infection by Beta and Gamma HPVs seems to be even more common than Alpha-HPVs. The latter is 5-7% in the general population, and increases up to 30% approximately in HIV-infected men who have sex with men. Despite major advances in the evaluation of oral HPV prevalence, its natural history is still little understood, especially for Beta and Gamma HPVs. The latest technologies, such as Next Generation Sequencing (NGS), can be exploited to gain new insights into oral HPV, and to improve the identification of novel HPV types.

Concurrent and Concordant Anal and Oral Human PapillomaVirus Infections Are Not Associated with Sexual Behavior in At-Risk Males.

Men who have sex with men (MSM) harbor the highest prevalence of anal and oral Human Papillomavirus (HPV) infection, particularly if HIV-infected. We investigated anal and oral HPV infections in HIV-infected and HIV-uninfected MSM, to assess concurrent (HPV detected at both sites, irrespective of the genotypes), and concordant infections (same genotype[s] detected at both sites). Matched anal and oral samples from 161 MSM (85 HIV-infected, and 76 HIV-uninfected) were tested with the Linear Array. Determinants of concurrent and concordant infections were evaluated using logistic regression. Anal infections were 4 to 7 times more frequent than oral infections in both study groups (p < 0.0001). Concurrent infections were not significantly different in HIV-infected (25.9%) and HIV-uninfected MSM (17.1%), p = 0.18. A concordant infection was found in 15 MSM (9.3%). Concordance was for one genotype in 14 individuals and for four genotypes in the remaining subject. In the overall population, only age was independently associated with a concurrent infection (AOR = 3.10, 95% CI: 1.34-7.19 for >39 vs. ≤39 years). None of the parameters of sexual behavior showed independent association with concordant infections. Among MSM, concordant anal and oral HPV infections do not seem to be explained by sexual behavior, but might derive from sequential acquisition by autoinoculation.