We aimed to determine the frequency of human papillomavirus-independent (HPVI) cervical squamous cell carcinoma (SCC) and to describe clinicopathologic characteristics. Among 670 patients with surgically treated SCCs in an established multi-institutional cohort, 447 had available tissue. Tissue microarrays were constructed and studied by in situ hybridization (ISH) for high-risk and low-risk human papillomavirus (HPV) mRNA and immunohistochemistry for p16 and p53. Tumors were HPVI if negative by HPV ISH and they failed to show diffuse p16 positivity by immunohistochemistry, and human papillomavirus-associated (HPVA) if positive by HPV ISH. Ten HPVI SCCs and 435 HPVA SCCs were identified; 2 cases were equivocal and excluded from analysis. The overall rate of HPVI SCC was low (2%) but was higher among older patients (7% in patients above 60 y of age and 17% in patients above 70 y of age). Compared with HPVA, patients with HPVI SCC were significantly older (median age, 72 vs. 49, P <0.001) and diagnosed at a higher stage (40% vs. 18% with stage III/IV disease, P =0.055). p53 expression was varied; 2 cases (20%) had null expression and 8 (80%) had wild-type expression. HPVI SCCs were heterogenous, with keratinizing, nonkeratinizing, and warty morphologies observed. Several cases had a precursor lesion reminiscent of differentiated vulvar intraepithelial neoplasia, with prominent basal atypia and hypereosinophilia or a basaloid-like morphology. Two patients (20%) had distant recurrences within 12 months, and 3 (30%) died of disease during follow-up. HPVI SCCs are rare tumors that are more common among older patients with higher stage disease and have important clinical and histologic differences from HPVA SCCs.

UNASSIGNED: Recurrent respiratory papillomatosis (RRP) is a benign, rare disease caused by Human Papilloma Virus (HPV) that can be divided into juvenile and adult forms. The course of the disease is variable, but is usually more aggressive in the juvenile form. The standard surgical treatment is represented by CO2 laser resection, although photoangiolytic lasers represent a valid alternative. Adjuvant therapies have been proposed for disease control in case of frequent surgical resections or spreading into the lower airways. In recent years, the development of immunotherapy led to the use of bevacizumab either intratumorally or intravenously, but the most promising therapeutic development is represented by HPV vaccination. This paper aims to present a narrative review of the literature and the experience of three different University Centres in the treatment of RRP.
UNASSIGNED: A retrospective analysis of the clinical charts of all patients affected by laryngeal papillomatosis and treated in three different University Centres between 2002 and 2022 was performed. The following parameters were collected: sex, age at first evaluation, sites of larynx involved, HPV type, type of first surgical treatment, presence and number of recurrences, surgical treatment of recurrences, adjuvant therapies, side effects and status at last follow-up.
UNASSIGNED: Seventy-eight patients were available for evaluation. Of these, 88% had adult onset RRP (Ao-RRP) and 12% juvenile onset RRP (Jo-RRP). The glottis was the most frequently involved subsite; all patients were submitted to surgical resection with CO2 laser under general anaesthesia. Recurrences appeared in 79% of the patients, the patients who did not recur were all adults. The mean number of recurrences was 9 (range 1-110). Recurrences were more frequent in children (M = 20; range 2-110) than adults (M = 5; range 1-21). Thirty-two (52%) of the 62 patients who recurred were re-treated with CO2 laser under general anaesthesia, while office-based treatment with a photoangiolytic laser was preferred in the remaining 30 (48%) patients. Adjuvant treatments were applied in 26 patients. The analysis of the course of the disease showed that in the 9 patients with Jo-RRP, 6 (67%) were free of lesions at the last follow-up, while the other 3 (33%) had papillomas. Of the 69 patients with Ao-RRP, 53 (77%) were alive and free of disease at the last visit, 14 (21%) were alive with disease, 1 (1%) was lost at follow-up and 1 (1%) died for other disease. Severe side effects were not observed except for 2 patients, who developed posterior glottic stenosis.
UNASSIGNED: Our results confirmed the literature review. RRP is a potentially aggressive disease, especially in juvenile onset. Surgical resection is still first-line treatment, but in case of multiple recurrences the use of adjuvant therapies must be taken into consideration.
La papillomatosi laringea ricorrente: strategie terapeutiche multimodali. Revisione della letteratura e analisi retrospettiva multicentrica.
UNASSIGNED: La papillomatosi recidivante delle vie respiratorie è una rara patologia benigna causata dal Papilloma virus umano (HPV) e può essere suddivisa in una forma giovanile ed una dell’adulto. Il decorso della malattia è variabile, di solito più aggressivo nella forma giovanile. Il trattamento chirurgico standard è rappresentato dalla resezione con laser CO2, anche se i laser fotoangiolitici possono rappresentare una valida alternativa. L’utilizzo di terapie adiuvanti è stato proposto per il controllo della malattia nei casi che richiedono trattamenti chirurgici frequenti o che tendono a diffondere nelle vie respiratorie inferiore. L’alfa-interferon è stato uno dei primi farmaci ad essere utilizzati, seguito dal cidofovir. Negli ultimi anni, lo sviluppo dell’immunoterapia ha condotto all’utilizzo del bevacizumab sia per somministrazione intralesionale o sistemica, ma lo sviluppo terapeutico più promettente è rappresentato dalla vaccinazione anti HPV. Lo scopo di questo lavoro è di presentare una revisione della letteratura e l’esperienza di tre differenti Centri Universitari nel trattamento della papillomatosi recidivante delle vie respiratorie.
UNASSIGNED: È stata condotta un’analisi retrospettiva sulle cartelle cliniche dei pazienti affetti da papillomatosi laringea e trattati in tre differenti Centri Universitari tra il 2002 e il 2022. Sono stati analizzati i seguenti parametri: sesso, età alla prima visita, siti laringei coinvolti, sierotipi di HPV, tipologia del primo trattamento chirurgico, presenza e numero di recidive, trattamento chirurgico delle recidive, terapie adiuvanti, effetti collaterali e status all’ultimo follow-up.
UNASSIGNED: Settantotto pazienti sono stati selezionati per lo studio. Di questi, l’88% presentava papillomatosi dell’adulto (Ao-RRP) e il 12% una forma giovanile (Jo-RRP). La glottide è risultata la sottosede più coinvolta; tutti i pazienti sono stati sottoposti a chirurgia con laser CO2 in anestesia generale. Recidive sono state osservate nel 79% dei pazienti, i pazienti che non hanno mostrato recidive erano tutti adulti. Il numero medio di recidive è stato di 9 (range 1-110). Le recidive sono risultate più frequenti nei bambini (M = 20; range 2-110); rispetto agli adulti (M = 5; range 1-21). Il 52% dei 62 pazienti con recidiva è stato ritrattato con laser CO2 laser in anestesia generale, mentre nell’altro 48% dei pazienti è stata scelta una procedura ambulatoriale con un laser fotoangiolitico. Terapie adiuvanti sono state impiegate in 26 pazienti. L’analisi del decorso della malattia ha rivelato che nei 9 pazienti con papillomatosi giovanile, 6 (67%) erano liberi da malattia all’ultimo follow-up, mentre gli altri 3 (33%) avevano ancora papillomi. Dei 69 pazienti con papillomatosi dell’adulto, 53 (77%) erano liberi da malattia all’ultima visita; 14 (21%) presentavano ancora papillomi; 1 (1%) è stato perso al follow-up e 1 (1%) è morto per altra malattia. Effetti collaterali severi sono stati riscontrati solo in 2 pazienti che hanno sviluppato una stenosi glottica posteriore.
UNASSIGNED: I risultati hanno confermato quelli della revisione della letteratura. La papillomatosi respiratoria ricorrente è una malattia potenzialmente aggressiva, specie nell’insorgenza giovanile. La resezione chirurgica è ancora il trattamento di prima linea, ma in caso di multiple recidive è necessario prendere in considerazione l’uso di terapie adiuvanti.

Human papillomavirus (HPV) is detected in 30-50% of invasive penile carcinomas, and it is frequently associated with basaloid and warty morphological features. Based on this heterogeneity and different clinical behaviors, we hypothesized a variation in their HPV genotypic composition. To test this, we evaluated 177 HPV-positive cases: basaloid (114), warty-basaloid (28), and warty (condylomatous) (35) invasive carcinomas. HPV DNA detection and genotyping was performed using the SPF-10/DEIA/LiPA25 system. Nineteen HPV genotypes were detected. High-risk HPVs predominated (96%), and low-risk HPVs were rarely present. Most common genotype was HPV16 followed by HPVs 33 and 35. According to the genotypes identified, 93% of the cases would be covered with current vaccination programs. There was a significant variation in the distribution of HPV16 and non-HPV16 genotypes according to histological subtype. HPV16 was significantly frequent in basaloid (87%) and was less frequent in warty carcinomas (61%). This molecular difference, along with their distinctive macro-microscopic and prognostic features, makes basaloid and warty carcinomas unique. The gradual decreasing frequency of HPV16 demonstrated in basaloid, warty-basaloid, and warty carcinomas suggest that the basaloid cell, present in those types in decreasing proportions, may be responsible for the differences.

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OBJECTIVE: This study aimed to analyze the clinicopathological features of ocular papilloma, a common benign tumor, and the risk factors related to its recurrence and partial deterioration.
METHODS: We collected and analyzed the clinical information of 298 patients (51.68% males) with mean age of 41.54 ± 21.95 years, in the ophthalmology department of the West China Hospital. Clinical and pathological factors that might be related to papilloma recurrence and partial deterioration were studied.
RESULTS: The top three papilloma sites were bulbar conjunctiva, eyelid skin and palpebral conjunctiva. Moreover, 3.59% of lesions presented a malignant transformation, and 16.28% of patients had one or more recurrences after an average follow-up of 4.47 years. The multivariate logistic regression model showed that multiple lesions were a risk factor for recurrence (p = 0.022, OR = 3.088, 95% CI: 1.180-8.079), while cryotherapy decreased the recurrence risk (p = 0.044, OR = 0.364, 95% CI: 0.136-0.972). Additionally, elderly patients and lesions on the corneal limbus or cornea had a higher risk of malignant transformation (p = 0.004 and 0.01, OR = 1.086 and 7.827, 95% CI: 1.027-1.150 and 1.629-37.596, respectively).
CONCLUSIONS: Ocular papilloma usually occurs in middle-aged and young patients, with no significant gender differences. Older patients and lesions on the corneal limbus or cornea are risk factors for partial malignant transformation. Finally, multiple lesions were a risk factor for recurrence, and cryotherapy reduced the recurrence rate.

Epidemiological data on the distribution of oral and maxillofacial diseases present in early childhood are scarce in the literature. This study analyzed the frequency of lesions biopsied in this region in children aged 0 to 3 years and sent for histopathological analysis in a reference oral pathology laboratory . Histopathological diagnostic data, lesion location, sex, and age were collected. Of the total of 93,950 records, 250 cases (0.27%) belonged to the age group from 0 to 3 years old. The most frequently diagnosed oral alterations were: mucocele (34/250; 13.6%); papilloma (11/250; 4.4%), giant cell fibroma (6/250; 2.4%), pyogenic granuloma (5/250; 2%) and hemangioma (3/250; 1.2%). The lip was the most affected site, followed by the gingiva and the tongue. These results generate information on the lesions most frequently diagnosed in early childhood, which facilitates the process of diagnosis and, consequently, treatment.

Conjunctival papilloma is often resistant to treatment. Various therapies have been reported with no gold standard. The purpose of this study was to compare treatment outcomes after various therapies.
A retrospective chart review of 30 conjunctival papilloma patients from 2009-2020. Data on demographics, tumour characteristics, primary treatment and outcomes were collected. The primary outcome was the frequency of complete tumour resolution and recurrence rate of each primary therapy. The secondary outcome was treatment related side effects.
The mean age was 57.5 years (3-93 years) with male predominance (n = 22, 73.3%). Eleven eyes were treated with interferon α-2b (IFN), seven with 5-fluorouracil (5FU), and 10 with excision biopsy and cryotherapy (6 with adjuvant therapy with IFN). The frequency of tumour resolution was 36.4% (4/11), 28.5% (2/7), and 100% (10/10) in each group, respectively. The mean time to resolution was faster in the surgical group compared to the medical group (1 day vs 159 days, p < 0.001). There was higher tumour recurrence with 11% in the surgical vs 0% in the medical group at 6 months and at 12 months, 22% recurrence in the surgical and 0% in the medical group (p = 0.52). However, the differences were not statistically significant.
Papilloma resolution is faster with surgical excision as compared to medical therapy. However, recurrences are more frequent after surgical versus medical treatment.

Recurrent respiratory papillomatosis is strictly connected with human papillomavirus (HPV) infection of the epithelium of the upper respiratory tract. The main treatment of lesions located in the larynx or lower pharynx includes microsurgical excision by using a CO2 laser. To decrease the amount of surgical procedures gain in importance combined therapy with antiviral agents. The aim of this study was to investigate the effect of the intralesional application of Cidofovir on the tissue of laryngeal papillomas. We have shown that simultaneous microsurgery with adjuvant therapy of Cidofovir reduces chronic inflammation (by measuring the expression of CD4 and CD8 in tissue samples), cell proliferation, and regulates the cell cycle of HPV-infected cells by reducing the expression of p53 and p63 proteins. In addition, this strategy reduces the multiple surgical procedures and regrowth of the pathology.

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There is uncertainty whether benign breast papillomas without atypia (BP) can be followed by imaging or require surgical resection.
A single-center, retrospective cohort study of patients diagnosed with BP (2011-2021) to determine the upgrade rate on surgery, and factors associated with surgical intervention and upgrade.
139 BPs were included. 27(19.4%) had upfront surgery; 112(80.6%) had imaging follow-up. The upfront surgery group had higher rates of pre-excision nipple inversion (n = 2(8.3%)vs.n = 0(0%),p = 0.003). In the imaging group, the median follow-up was 3.8years, and 9 had subsequent resection. Upgrade rate was 5.8%(8/139). Of all BPs undergoing surgery (n = 36), patients ≥60years (75.0%vs.25.0%,p = 0.049) or with family history of breast cancer (87.5%vs.48.1%,p = 0.048) were more likely to have upgrade.
Despite a low number of events, this study supports radiologic follow-up of BP except in patients ≥60 years or with family history of breast cancer, adding to the growing body of evidence supporting watchful waiting of BPs.