Bilobed flap reconstruction after en-bloc removal of solitary fibrous tumor of the lacrimal sac.

Purpose: To report a rare case of a solitary fibrous tumor (SFT) of the lacrimal sac and discuss considerations for management of similar cases. Observations: We present the case of a 41-year-old woman who presented with a primary lacrimal sac SFT for which she underwent en-bloc surgical resection. We discuss management options for SFTs and our surgical approach for this case: bilobed flap reconstruction of the medial canthus and inferior orbit. Conclusions: We present an uncommon presentation of a rare tumor and a successful one-stage reconstruction with a bilobed flap.

Metastatic neuroendocrine tumors mimicking as primary ocular disease.

PURPOSE: To report two cases of metastatic neuroendocrine tumors masquerading as primary ocular disease. OBSERVATIONS: Case 1 is a 38-year-old man who was referred with subacute onset diplopia and fluctuating ptosis suggestive of myasthenia gravis. Case 2 is a 21-year-old man who presented with blurry vision and was found to have a pigmented ciliary body mass and retinal detachment suggestive of uveal melanoma. Both patients were ultimately diagnosed with metastatic neuroendocrine tumors. CONCLUSIONS AND IMPORTANCE: Neuroendocrine tumors, though rare and infrequently metastatic to the eye and orbit, can initially present with ocular signs. A broad differential and careful consideration of ocular and systemic symptoms are critical in such challenging cases.

p16(INK4A) expression in invasive laryngeal cancer.

We examined p16 expression in tumors from a population-based sample of laryngeal cancer cases diagnosed in the U.S. Samples had been previously genotyped for HPV DNA. Overall, p16 expression was observed in laryngeal tissue from 8 of 101 (7.9%) cases. p16 expression was observed in 2 of 16 (12.5%) cases previously determined to be HPV DNA positive. The two cases dually positive for p16 and HPV DNA were non-keratinizing SCC and papillary SCC tumors that were positive for genotypes 18 and 35/89, respectively. Positivity for p16 and/or HPV DNA was not associated with 5-year survival (log-rank p value= 0.55). Our findings support a limited role of HPV in laryngeal carcinogenesis. p16 is not a reliable surrogate for HPV status in laryngeal cancers and is not a predictor of laryngeal cancer survival.

US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines.

BACKGROUND: This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. METHODS: The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. RESULTS: HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. CONCLUSIONS: In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine.

Human papillomavirus prevalence in invasive laryngeal cancer in the United States.

PURPOSE: Human papillomavirus (HPV) is a major risk factor for specific cancers of the head and neck, particularly malignancies of the tonsil and base of the tongue. However, the role of HPV in the development of laryngeal cancer has not been definitively established. We conducted a population-based, cancer registry study to evaluate and characterize the genotype-specific prevalence of HPV in invasive laryngeal cancer cases diagnosed in the U.S. METHODS: The presence of genotype-specific HPV DNA was evaluated using the Linear Array HPV Genotyping Test and the INNO-LiPA HPV Genotyping Assay in formalin-fixed paraffin embedded tissue from 148 invasive laryngeal cancer cases diagnosed in 1993-2004 within the catchment area of three U.S. SEER cancer registries. RESULTS: HPV DNA was detected in 31 of 148 (21%) invasive laryngeal cancers. Thirteen different genotypes were detected. Overall, HPV 16 and HPV 33 were the most commonly detected types. HPV was detected in 33% (9/27) of women compared with 18% (22/121) of men (p = 0.08). After adjustment for age and year of diagnosis, female patients were more likely to have HPV-positive laryngeal tumors compared to males (adjusted OR 2.84, 95% CI 1.07-7.51). Viral genotype differences were also observed between the sexes. While HPV 16 and 18 constituted half of HPV-positive cases occurring in men, among women, only 1 was HPV 16 positive and none were positive for HPV 18. Overall 5-year survival did not vary by HPV status. CONCLUSIONS: HPV may be involved in the development of a subset of laryngeal cancers and its role may be more predominant in women compared to men.

Human papillomavirus genotype prevalence in invasive vaginal cancer from a registry-based population.

OBJECTIVE: To describe the human papillomavirus (HPV) genotype distribution in invasive vaginal cancers diagnosed before the introduction of the HPV vaccine and evaluate if survival differed by HPV status. METHODS: Four population-based registries and three residual tissue repositories provided formalin-fixed, paraffin-embedded tissue from microscopically confirmed primary vaginal cancer cases diagnosed between 1994 and 2005 that were tested by L1 consensus polymerase chain reaction with type-specific hybridization in a central laboratory. Clinical, demographic, and all-cause survival data were assessed by HPV status. RESULTS: Sixty cases of invasive vaginal cancer were included. Human papillomavirus was detected in 75% (45) and 25% (15) were HPV-negative. HPV 16 was most frequently detected (55% [33/60]) followed by HPV 33 (18.3% [11/60]). Only one case was positive for HPV 18 (1.7%) Multiple types were detected in 15% of the cases. Vaginal cancers in women younger than 60 years were more likely to be HPV 16- or HPV 18-positive (HPV 16 and 18) than older women, 77.3% compared with 44.7% (P=.038). The median age at diagnosis was younger in the HPV 16 and 18 (59 years) group compared with other HPV-positive (68 years) and no HPV (77 years) (P=.003). The HPV distribution did not significantly vary by race or ethnicity or place of residence. The 5-year unadjusted all-cause survival was 57.4% for women with HPV-positive vaginal cancers compared with 35.7% among those with HPV-negative tumors (P=.243). CONCLUSION: Three fourths of all vaginal cancers in the United States had HPV detected, much higher than previously found, and 57% could be prevented by current HPV vaccines.

Human papillomavirus genotype prevalence in invasive penile cancers from a registry-based United States population.

BACKGROUND: Human papillomavirus (HPV) is estimated to play an etiologic role in 40-50% of penile cancers worldwide. Estimates of HPV prevalence in U.S. penile cancer cases are limited. METHODS: HPV DNA was evaluated in tumor tissue from 79 invasive penile cancer patients diagnosed in 1998-2005 within the catchment areas of seven U.S. cancer registries. HPV was genotyped using PCR-based Linear Array and INNO-LiPA assays and compared by demographic, clinical, and pathologic characteristics and survival. Histological classification was also obtained by independent pathology review. RESULTS: HPV DNA was present in 50 of 79 (63%) of invasive penile cancer cases. Sixteen viral genotypes were detected. HPV 16, found in 46% (36/79) of all cases (72% of HPV-positive cases) was the most prevalent genotype followed equally by HPV 18, 33, and 45, each of which comprised 5% of all cases. Multiple genotypes were detected in 18% of viral positive cases. HPV prevalence did not significantly vary by age, race/ethnicity, population size of geographic region, cancer stage, histology, grade, penile subsite, or prior cancer history. Penile cases diagnosed in more recent years were more likely to be HPV-positive. Overall survival did not significantly vary by HPV status. CONCLUSION: The relatively high prevalence of HPV in our study population provides limited evidence of a more prominent and, possibly, increasing role of infection in penile carcinogenesis in the U.S. compared to other parts of the world.

Prevalence of human papillomavirus types in invasive cervical cancers from 7 US cancer registries before vaccine introduction.

OBJECTIVE: We conducted a baseline study of human papillomavirus (HPV) type prevalence in invasive cervical cancers (ICCs) using data from 7 cancer registries (CRs) in the United States. Cases were diagnosed between 1994 and 2005 before the implementation of the HPV vaccines. MATERIALS AND METHODS: Cancer registries from Florida, Kentucky, Louisiana, Michigan, Hawaii, Iowa, and Los Angeles, California identified eligible ICC cases and obtained sections from representative blocks of archived tumor specimens for DNA extraction. All extracts were assayed by linear array and, if inadequate or HPV negative, retested with INNO-LiPA Genotype test. Clinical and demographic factors were obtained from the CRs and merged with the HPV typing data to analyze factors associated with different types and with HPV negativity. RESULTS: A total of 777 ICCs were included in this analysis, with broad geographic, age, and race distribution. Overall, HPV was detected in 91% of cases, including 51% HPV-16, 16% HPV-18 (HPV-16-negative), and 24% other oncogenic and rare types. After HPV-16 and -18, the most common types were 45, 33, 31, 35, and 52. Older age and nonsquamous histology were associated with HPV-negative typing. CONCLUSIONS: This study provides baseline prevaccine HPV types for postvaccine ICC surveillance in the future. HPV-16 and/or -18 were found in 67% of ICCs, indicating the potential for vaccines to prevent a significant number of cervical cancers.

Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction.

OBJECTIVE: The study aimed to determine the baseline prevalence of human papillomavirus (HPV) types in invasive vulvar cancer (IVC) and vulvar intraepithelial neoplasia 3 (VIN 3) cases using data from 7 US cancer registries. MATERIALS AND METHODS: Registries identified eligible cases diagnosed in 1994 to 2005 and requested pathology laboratories to prepare 1 representative block for HPV testing on those selected. Hematoxylin-eosin-stained sections preceding and following those used for extraction were reviewed to confirm representation. Human papillomavirus was detected using L1 consensus polymerase chain reaction (PCR) with PGMY9/11 primers and type-specific hybridization, with retesting of samples with negative and inadequate results with SPF10 primers. For IVC, the confirmatory hematoxylin-eosin slides were re-evaluated to determine histological type. Descriptive analyses were performed to examine distributions of HPV by histology and other factors. RESULTS: Human papillomavirus was detected in 121/176 (68.8%) cases of IVC and 66/68 (97.1%) cases of VIN 3 (p < .0001). Patients with IVC and VIN 3 differed by median age (70 vs 55 y, p = .003). Human papillomavirus 16 was present in 48.6% of IVC cases and 80.9% of VIN 3 cases; other high-risk HPV was present in 19.2% of IVC cases and 13.2% of VIN 3 cases. Prevalence of HPV differed by squamous cell carcinoma histological subtype (p < .0001) as follows: keratinizing, 49.1% (n = 55); nonkeratinizing, 85.7% (n = 14), basaloid, 92.3% (n = 14), warty 78.2% (n = 55), and mixed warty/basaloid, 100% (n = 7). CONCLUSIONS: Nearly all cases of VIN 3 and two thirds of IVC cases were positive for high-risk HPV. Prevalence of HPV ranged from 49.1% to 100% across squamous cell carcinoma histological subtypes. Given the high prevalence of HPV in IVC and VIN 3 cases, prophylactic vaccines have the potential to decrease the incidence of vulvar neoplasia.

Association of prion protein expression with pancreatic adenocarcinoma survival in the SEER residual tissue repository.

Pancreatic ductal adenocarcinoma (PDAC) is an important cause of cancer death with no clear prognostic biomarker. Expression of prion (PrP) has been reported to be a marker of poor prognosis in a series of Caucasian PDAC cases. We determined the prognostic value of PrP in a racially and geographically diverse population-based series of PDAC cases. PrP expression was examined in 142 PDAC cases from three cancer registries. Cases included 71 Caucasian, 54 Asian/Pacific Islanders and 17 Blacks diagnosed from 1983-2000, and followed through 2008. Hazard ratios (HR) and 95% confidence intervals (CIs) for the association of PrP expression with survival were computed after adjustment for case attributes. The risk of death was about four times higher (HR=3.8; 95% PDAC cases with PrP(+) tumors (median survival 5 months) compared to the 34 cases with PrP(-) tumors (median survival 20 months). Of 51 cases with resected, localized PDAC median survival was 74 months for 17 cases with PrP(-) tumors versus 14 months for 34 cases with PrP(+) tumors (HR=6.7; 95% CI: 2.6, 17.4). All 6 surviving cases had PrP(-) negative tumors (median survival, > 10 years). PrP may have potential as a prognostic biomarker in PDAC patient management.