Studies of human papillomavirus (HPV) in urological tumors

Urological tumors were examined for the presence of human papillomavirus (HPV) DNA by using Southern blot hybridization. In 20 male patients with condyloma acuminatum, HPV type 6 was found at 85% (17/20), HPV type 11 at 95% (19/20), HPV type 16 at 5% (1/20) and HPV type 18 at 0% (0/20). In 2 female patients with condyloma acuminatum, HPV types 6, 11, 16 and 18 were found at 100% (2/2), 100% (2/2), 50% (1/2) and 0% (0/2), respectively. All 6 of the patients who were positive for HPV type 6, were also positive for HPV type 11. Two patients were positive for HPV types 6, 11 and 16, the last of which was frequently found in penile cancer and uterine cervical cancer. In 6 patients with penile cancer, two patients were positive for HPV type 16 and negative for HPV types 6, 11 and 18. The remaining 4 patients were negative for all these HPV types. One patient who was positive for HPV type 16 had penile cancer after three previous episodes of penile condyloma acuminatum. From this information, a malignant change in the condyloma acuminatum was assumed to indicate the possible association of HPV type 16 with the process of malignant degeneration. HPV types, 6, 11, 16 and 18 were not detected in a female patient with vulvar cancer. Although HPV was thought to participate in the development of urological tumors except for external genital tumors, all patients examined, consisting of 2 with benign prostatic hypertrophy, 5 with prostatic cancer and 24 with bladder cancer, were negative for HPV types 6, 11, 16 and 18. Eight patients with bladder cancer were negative for HPV type 33.     

Human papillomavirus infections in laryngeal cancer

Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we review the currently known associations of HPV infections in diseases of the larynx and their potential for oncogenicity. Using several methods of detection, HPV DNA has been detected in benign (papillomatosis), indolent (verrucous carcinoma), and malignant (squamous cell carcinoma) lesions of the larynx. Consistent with the known oncogenic risk of HPV infections, common HPV types associated with laryngeal papillomatosis include low‐risk HPV types 6 and 11, with high‐risk HPV types 16 and 18 more commonly present in neoplastic lesions (verrucous carcinoma and squamous cell carcinoma). Although a broad range of prevalence has been noted in individual studies, approximately 25% of laryngeal squamous cell carcinomas harbor HPV infections on meta‐analysis, with common involvement of high‐risk HPV types 16 (highest frequency) and 18. Preliminary results suggest that these high‐risk HPV infections seem to be biologically relevant in laryngeal carcinogenesis, manifested as having viral DNA integration in the cancer cell genome and increased expression of the p16 protein. Despite this knowledge, the clinical significance of these infections and the implications on disease prevention and treatment are unclear and require further investigation. © 2010 Wiley Periodicals, Inc. Head Neck, 2011     

Anti-papillomavirus vaccines and prevention of cervical cancer: progress and prospects

Human papillomaviruses (HPV) cause the development of various cutaneous and mucosal lesions. Some genotypes play a role in the genesis of cervical cancer, which is the second most common cancer in women. HPV types 16 and 18 account for 60 to 72% of all HPV-associated cervical cancers, while types 6 and 11 cause genital warts. Despite the various escape strategies viruses use to fight the natural immune system, more than 90% of the infections clear spontaneously. It should therefore be possible to prepare prophylactic vaccines. The HPV major capsid protein L1 self-assembles into virus-like particles (VLP). Immunization after parenteral vaccination with it provided very good protection against experimental infection in different animal models. The first clinical trials revealed the satisfactory tolerance and excellent immunogenicity of these vaccines. Two vaccine approaches were selected: one based on protection against cervical cancer from a bivalent VLP L1 vaccine containing the two genotypes most frequently involved in cervical cancer (type 16 and 18) and the other, protecting against warts as well as cervical cancer, with a quadrivalent HPV VLP L1 vaccine containing genotypes 6, 11, 16 and 18. Initial results with these vaccines show an efficacy of more than 90% against infection and 100% against the onset of dysplastic lesions. Despite these hopeful results, a vaccined strategy sould still be defined. Meanwhile, the cytology screening program should be carried on until the beginning of the vaccination.     

Heterologous Immune Responses to Influenza Vaccine in Kidney Transplant Recipients

Influenza vaccine is known to have suboptimal immunogenicity in transplant recipients. Despite this, influenza vaccine may have the added benefit of inducing a cross‐reactive immune response to viral strains not found in the vaccine. This is termed “heterologous immunity” and has not been assessed previously in transplant patients. Pre‐ and postvaccination sera from kidney transplant recipients (n = 60) immunized with the 2012–2013 adjuvanted or nonadjuvanted influenza vaccine underwent testing by hemagglutination inhibition assay for strains not present in vaccine: A/New Caledonia/20/99 (H1N1), A/Texas/50/2012 (H3N2) and B/Brisbane/60/2008. The geometric mean titer of antibody to heterologous strains increased after vaccine (H1N1: 80.0 to 136.1, p < 0.001; H3N2: 23.3 to 77.3, p < 0.001; B: 13.3 to 19.5, p < 0.001). Seroconversion rates were 16.7%, 41.7%, and 13.3%, respectively. No differences in heterologous response were seen in the adjuvanted versus nonadjuvanted groups. Patients were more likely to seroconvert for a cross‐reactive antigen if they seroconverted for the specific vaccine antigen. Seroconversion to heterologous A/H3N2, for example, was 84.0% for homologous H3N2 seroconverters versus 11.4% for nonseroconverters (p < 0.001). This study provides novel evidence that transplant recipients are able to mount significant cross‐protective responses to influenza vaccine that may be an additional, previously unknown benefit of immunization.     

Randomized Controlled Trial of High‐Dose Intradermal Versus Standard‐Dose Intramuscular Influenza Vaccine in Organ Transplant Recipients

The immunogenicity of standard intramuscular (IM) influenza vaccine is suboptimal in transplant recipients. Also, recent studies suggest that alloantibody may be upregulated due to vaccination. We evaluated a novel high‐dose intradermal (ID) vaccine strategy. In conjunction, we assessed alloimmunity. Transplant recipients were randomized to receive IM or high‐dose ID vaccine. Strain‐specific serology and HLA alloantibody production was determined pre‐ and postimmunization. In 212 evaluable patients (105 IM, 107 ID), seroprotection to H1N1, H3N2 and B strains was 70.5%, 63.8% and 52.4% in the IM group, and 71.0%, 70.1%, 63.6% in the ID group (p = ns). Seroconversion to ≥1 antigen was 46.7% and 51.4% in the IM and ID groups respectively (p = 0.49). Response was more likely in those ≥6 months posttransplant (53.2% vs. 19.2%; p = 0.001). Use of mycophenolate mofetil was inversely associated with vaccine response in a dose‐dependent manner (p < 0.001). Certain organ subgroups had higher response rates for influenza B in the ID vaccine group. Differences in anti‐HLA antibody production were detected in only 3/212(1.4%) patients with no clinical consequences. High‐dose intradermal vaccine is an alternative to standard vaccine and has potential enhanced immunogenicity in certain subgroups. In this large cohort, we also show that seasonal influenza does not result in significant alloantibody production.     

Association of DNA aneuploidy with human papillomavirus-induced malignant transformation of sinonasal transitional papillomas

The nuclear DNA content of 19 transitional papillomas of the sinonasal region and 9 maxillary squamous cell carcinomas was studied by flow cytometry; the presence of human papillomavirus (HPV) DNA types 11 and 16 was determined by the in situ hybridization technique from paraffin-embedded tissue. Thirteen (68%) of the papillomas and none of the carcinomas contained HPV genome. Six (32%) of the papillomas and 4 (44%) of the carcinomas had an aneuploid DNA content. The relative DNA content (DNA index) of the aneuploid maxillary carcinomas was larger than that of aneuploid papillomas (p = 0.004). Three of the papillomas underwent malignant transformation, all three of which contained HPV type 16 DNA; two were also aneuploid. Data indicate that papillomas containing HPV type 16 DNA have a tendency (p = 0.06) to undergo malignant transformation, and that this tendency is greater if DNA aneuploidy or HPV type 11 DNA is also present (p = 0.02).     

Human papillomavirus infection and anogenital condyloma in bone marrow transplant recipients

BACKGROUND: Secondary malignant diseases are late complications after allogeneic bone marrow transplantation (BMT). Anogenital lesions associated with human papillomavirus (HPV) infection have been described in renal transplant recipients but not after BMT. HPV types 16 and 18 are strongly linked to the malignant transformation. METHODS: In a series of 238 patients with allogeneic BMT, three had anogenital lesions. We looked for HPV in DNA extracted from embedded tissue to study HPV genotypes, p53 expression, and ploidy. RESULTS: In two patients, HPV sequences were detected. One of them, with giant condyloma, had HPV type 18 and two aneuploid clones, but p53 expression was not found. CONCLUSION: As in solid organ transplant recipients, anogenital condyloma may develop after BMT. Because the oncoprotein of HPV is able to bind and to degrade p53, it may lead to genetic instability, and subsequently to malignant transformation.     

Reactivation of Latent HPV Infections After Renal Transplantation

Female renal transplant recipients (RTRs) have an increased risk for developing human papillomavirus (HPV)–related (pre)malignant lesions of the genital tract. This study aims to assess the genital prevalence of HPV before and after renal transplantation (RT). In female patients who were counseled for RT at the Radboud University Medical Center Nijmegen, the Netherlands, gynecological examination was performed at first visit, and 1 and 2 years later. HPV self‐sampling and questionnaires on sexual behavior were performed every 3 months. In 65 patients who underwent RT, the high‐risk human papillomavirus (hrHPV) prevalence as assessed with the highly sensitive SPF₁₀ ‐LiPA₂₅ test increased significantly from 19% before to 31% after RT (p = 0.045). Based upon the clinically validated Cobas 4800 HPV test, the hrHPV prevalence increased from 10% before to 14% after RT (p = 0.31). During follow‐up, no changes in sexual behavior were reported. Thirty‐three patients who did not undergo RT showed a hrHPV prevalence of 21% at study entry and of 27% after 12 months with the sensitive test, and a stable prevalence of 16% with the clinically validated test. The results of this study indicate that activation of latent HPV infections may contribute to the increased risk of HPV‐related (pre)malignant lesions in female RTRs.     

某院1 715例妇科就诊者人乳头瘤病毒感染率及基因型分布

目的分析妇科就诊人群人乳头瘤病毒(HPV)感染率及基因型分布,为宫颈癌的诊治及HPV疫苗的研制提供参考。 方法采用凯普医用核酸分子快速导流杂交基因芯片技术(Hybrimax)检测2009年11月至2016年10月宝鸡市中医医院门诊及住院的1 715例自愿接受生殖道HPV感染筛查且有性生活史妇女的21种HPV基因型别。 结果就诊人群宫颈感染HPV高危型以HPV58、HPV16、HPV52和HPV33型最为常见,而HPV低危型则以HPV11及CP8304为主。1 715例就诊者中266例HPV阳性,阳性率为15.51%。其中单一感染者168例(9.80%),双重及多重感染者98例(5.71%);就诊者以31～40岁和41～50岁年龄段HPV感染率较高,分别为18.31%和18.60%;其次为≤30岁就诊者,感染率为13.92%;>50岁患者HPV感染率较低(8.24%),与≤30岁患者相比差异具有统计学意义(P均<0.05)。168例单一高危型HPV感染者以HPV58、HPV16、HPV52、HPV33型感染为主,分别为68例(40.48%)、40例(23.81%)、22例(13.10%)、10例(5.95%),与HPV58型阳性率比较,HPV16、HPV52、HPV33型的阳性率差异均有统计学意义(P均<0.05);低危型HPV感染者以HPV11型和CP8304感染为主,分别为16例(9.52%)和12例(7.14%),差异无统计学意义(χ²= 1.512、P= 0.186)。98例双重及多重HPV感染者中双重感染者62例(63.27%);三重感染者28例(28.57%);四重感染者8例(8.16%)。双重及多重HPV感染亚型主要以HPV58、HPV16、HPV52和HPV11型为主,分别为25例(25.51%)、20例(20.41%)、16例(16.33%)和11例(11.22%)。 结论本院妇科就诊人群高危型HPV感染率基本符合亚洲人群分布规律,但存在一定区域性。     

Immunogenicity and Safety of an Intradermal Boosting Strategy for Vaccination Against Influenza in Lung Transplant Recipients

The immunogenicity of influenza vaccine is suboptimal in lung transplant recipients. Use of a booster dose and vaccine delivery by the intradermal rather than intramuscular route may improve response. We prospectively evaluated the immunogenicity and safety of a 2-dose boosting strategy of influenza vaccine. Sixty lung transplant recipients received a standard intramuscular injection of the 2006-2007 inactivated influenza vaccine, followed 4 weeks later by an intradermal booster of the same vaccine. Immunogenicity was assessed by measurement of geometric mean titer of antibodies after both the intramuscular injection and the intradermal booster. Vaccine response was defined as 4-fold or higher increase of antibody titers to at least one vaccine antigen. Thirty-eight out of 60 patients (63%) had a response after intramuscular vaccination. Geometric mean titers increased for all three vaccine antigens following the first dose (p < 0.001). However, no significant increases in titer were observed after the booster dose for all three antigens. Among nonresponders, 3/22 (13.6%) additional patients responded after the intradermal booster (p = 0.14). The use of basiliximab was associated with a positive response (p = 0.024). After a single standard dose of influenza vaccine, a booster dose given by intradermal injection did not significantly improve vaccine immunogenicity in lung transplant recipients.     

Prevalence of human papillomavirus infection in the urinary tract of men with urethritis

Objectives: To investigate the prevalence of human papillomavirus (HPV) in the genital and urinary tract of men with urethritis. Methods: Cell samples were collected from the penis, urethra and urine of 142 men with urethritis. A HPV test was performed on the samples using the modified GP5+/6+ polymerase chain reaction method, and the HPV genotype was determined using a HPV GenoArray test. Results: Out of 142 urethritis patients, HPV was detected in 48% (68 cases), and high‐risk HPV was found in 32% (46 cases) of patients, on their penis or in the urinary tract (urethra or urine). HPV was detected in 31% in the penis, 20% in the urethra and 24% in the urine, while high‐risk HPV was identified in 23% in the penis, 12% in the urethra and 11% in the urine. Among the HPV‐positive men, 66% had HPV infection in the urinary tract where the most common HPV types were HPV6, HPV16, HPV18 and HPV58. Single HPV‐type infection was more frequently found in the urinary tract (89%) than in the penis (65%) (P < 0.05). Conclusions: Similar to the penis, the urinary tract represents a common HPV infection site in men with urethritis.     

Detection of human papillomavirus DNA in cancer of the urinary bladder by in situ hybridisation.

The association of the human papillomavirus (HPV) with cancer of the urinary bladder was assessed by in situ hybridisation using probes selective for HPV types 6/11 and 16/18 DNA. No hybridisation signal was detected with the type 6/11 probe on 100 formalin-fixed, paraffin-embedded bladder tumours sampled. However, when the same samples were hybridised with the HPV type 16/18 DNA probe, 11 of 66 (16.6%) papillary and 1 of 10 (10%) solid transitional cell carcinomas gave positive signals. These results suggest the involvement of HPV in cancer of the bladder, although the frequency of multiple HPV types in these tumours is uncertain.     

Human Papillomaviruses in Transplant-Associated Skin Cancers

Background. Human papillomavirus (HPV) infection has been suggested to be involved in the development of nonmelanoma skin cancer, the most common malignancy after solid-organ transplantation.
Objective. The objective of this study was to analyze the prevalence of different HPV types in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) of transplant recipients and nonimmunosuppressed patients.
Methods. To include the complete spectrum of HPV types in skin lesions, a comprehensive polymerase chain reaction assay with five different primer combinations was used.
Results. For SCC, HPV DNA was detected more frequently in tumors of transplant recipients (12/16, 75%) than of nonimmunosuppressed patients (7/19, 37%). In contrast, the HPV detection rate was similar in BCC specimens (4/8 or 50% in transplanted patients; 27/56 or 48% in nonimmunosupressed patients). Overall, 22 different HPV types were identified. HPV types 5 and 8 were detected predominately in SCC from transplant recipients. The amount of viral DNA was slightly higher in SCC of transplanted than in nonimmunosuppressed patients, but much lower than in both cutaneous and genital warts.
Conclusions. Cutaneous infections with HPV5 and HPV8 may represent an increased risk for SCC development in transplant recipients. The mechanisms by which these viruses may contribute to skin cancer development still remain unclear.     

Human papilloma virus DNA and p53 mutation analysis on bladder washes in relation to clinical outcome of bladder cancer

OBJECTIVES: High-risk human papilloma virus (HPV) types stimulate degradation and deactivation of protein associated with the p53 tumour suppressor gene via the ubiquitin-dependent pathway. For a long time, changes of the p53 tumour suppressor gene have been correlated with poor clinical outcome in patients with superficial bladder cancer. We aimed to study the association between presence of (high-risk) HPV DNA, p53 status, and clinical outcome in bladder cancer patients. This study must be seen as a preliminary study to investigate this potentially important problem. MATERIAL AND METHODS: From 107 patients, 166 bladder wash samples were obtained. p53 status was determined by mutation analysis, HPV detection, and genotyping by the SPF(10)-LiPA assay. Clinical data were abstracted from the medical files. RESULTS: The prevalence of all-type and high-risk HPV infection in malignancies of the bladder was 15.2% and 8.1%, respectively. In high-grade tumours this prevalence was 18.2% and 10.6%, respectively. In grade 1, 2 and 3 tumours the infection rate of high-risk HPV types was 0%, 3.3%, and 10.6%, respectively (trend test: p=0.221). In Ta, T1, and T2-T4 tumours the high-risk HPV infection rate was 0%, 12.5% and 18.2%, respectively (trend test: p=0.045). In the p53 wild-type patients who showed progression, 1 of 9 patients had a high-risk type HPV infection. In the group of wild-type patients who showed no progression, 4 of 37 patients had a high-risk type HPV infection (odds ratio: 1.03; 95% confidence interval, 0.1-10.5). CONCLUSIONS: The data of this pilot study show the suggestion of a positive trend in the correlation between tumour grade/stage and high-risk type HPV infection. However, no additional risk for progression is found for p53 wild-type patients with a high-risk HPV infection.     

Prevalence of HPV DNA in cervical specimens in women with renal transplants: a comparison with dialysis-dependent patients and patients with renal impairment

The aim of this study was to assess the prevalence of humanpapillomavirus (HPV) DNA in women who had received a renal transplantand to compare this with two control groups. Women who had a functioning renal transplant for greater than6 months (n = 69) were compared with women on maintenance dialysis(n = 89) and women with impaired renal function (creatinine0.15-0.39 mmol/l) (n=22). Women were excluded if they had hada hysterectomy, were older than 65 years, or were not yet sexuallyactive. A questionnaire and cervical scrape were obtained fromeach participant. The cervical scrape was analysed for HPV DNAusing PCR and the Li consensus primers. The participation rate of transplant patients, dialysis patientsand those with impaired renal function ("normal" group) was69, 68, and 78% respectively. The characteristics of the threegroups of women at enrollment were similar. No cytological abnormalitieswere present in the "normal" population but 11 of 89 patientson maintenance dialysis and nine of 69 transplant patients hadcytological abnormalities of atypia or greater (P=0.08 and P=0.07,for "normal" compared to dialysis and transplant groups respectively).One (4.5%) of the "normal" women had evidence of HPV DNA, while18 (20%) of patients on maintenance dialysis and 15 (22%) oftransplant patients were positive (P=0.07 and P=0.05, for "normal"compared to dialysis and transplant groups respectively). This study suggests that not only transplant recipients butalso dialysis patients may have a higher prevalence of riskfactors (cytological abnormalities and HPV DNA) for the developmentof cervical cancer.     

某医院机会性筛查女性人乳头瘤病毒感染流行病学分布及对人乳头瘤病毒疫苗认知调查

目的调查医院门诊机会性筛查女性人乳头瘤病毒（HPV）感染流行病学分布和对预防性疫苗的认知情况,为本院宫颈病变防治提供依据。 方法收集2017年1月至2017年12月于湖北医药学院附属随州医院妇科门诊行HPV筛查的女性患者的流行病学资料,采用问卷调查以了解其对HPV感染及疫苗接种的认知情况。 结果本院门诊机会性筛查女性HPV感染率为16.55%（143/864）。不同年龄组女性HPV感染率差异有统计学意义（χ² = 23.61、P < 0.001）。HPV感染基因型以单一型感染多见（73.43%）;多重感染占26.57%（38/143）;高危型感染占70.63%,以HPV 16型、58型和52型多见,低危型占29.37%,以HPV 81型、11型和42型多见。在问卷调查中,女性对于HPV感染的认知与年龄和文化程度有关（χ² = 70.89、70.63,P均< 0.001）,与居住地无关（χ² = 1.85、P = 0.17）。27.39%（309/1 128）人群知晓HPV感染,20.12%（227/1 128）知晓HPV疫苗,37.59%（424/1 128）人群愿意接种HPV疫苗,其中仅12%（51/424）愿意自费接种;疫苗价位是影响HPV疫苗接受度的主要因素。 结论本医院机会性筛查女性人群HPV感染率较高,同时对HPV认知和预防意识较低。应加强HPV筛查的普查力度,积极推广HPV疫苗的知晓率和接受度。     

Human papillomavirus-associated early vulvar neoplasia investigated by in situ hybridization

Of 21 consecutive cases of early vulvar neoplasia studied at the Istituto Nazionale Tumori of Milan, 62% appeared to be related to papillomavirus infection. This conclusion is the result of the present study by in situ hybridization with DNA probes of human papillomavirus (HPV) 6/11, 16, and 18 and of previous ultrastructural and immunohistochemical investigations. The proportion of cases associated with HPV was 78.5% for those (11/14) with histologic evidence of viral infection and 33% for those without (2/6). HPV 16 was detected in all cases that were positive by in situ hybridization except for one, which showed HPV 6/11 DNA. In one case there was a mixed triple infection for HPV 6/11, 16, and 18. The patient who was positive for HPV 6/11 had a giant condyloma associated with an inguinal lymph node containing a metastatic well-differentiated squamous cell carcinoma. Three cases were positive for papillomavirus internal capsid species-nonspecific antigen (PV-Ag) (with ultrastructural evidence of virions in one of them) and were negative for HPV-DNA hybridization. They appeared to be infected with a type of HPV not identified by the available probes. Three cases, and two sites of two other cases with double infection, were HPV-DNA-positive and PV-Ag-negative. They illustrate the limitation of immunohistochemical investigation in cases with high-grade intraepithelial neoplasia. Six cases of verrucous carcinoma of the vulva were negative for HPV DNA by in situ hybridization.     

Initial prevalence of anal human papilloma virus infection in liver transplant recipients

Although liver transplant recipients are at increased risk of human papilloma virus (HPV)‐related anal cancer, limited data are available regarding the initial prevalence of anal HPV infection in this population. Anal swabs collected from 50 liver transplant recipients within the first three postoperative weeks were subjected to real‐time polymerase chain reaction for detection of the four HPV genotypes: 6, 11, 16, and 18. Predictors of any, low‐risk, and high‐risk anal HPV infection were evaluated. Overall, the prevalence of any anal HPV infection was 18.0%, with the corresponding rates for high‐ and low‐risk HPV genotypes being 8.0% and 10.0%, respectively. Infection with any type of anal HPV was higher in patients with hepatitis B virus (HBV) infection (P = 0.027), ≥3 sexual partners (P = 0.031), and alcoholic liver disease (P = 0.063). HBV infection was the only factor significantly associated with high‐risk HPV infection (P = 0.038). Male sex (P = 0.050), age ≥52 years (P = 0.016), ≥30 sexual partners (P = 0.003), age at first intercourse ≤18 years (P = 0.045), and time since first intercourse ≥38 years (P = 0.012) were identified as predictors of low‐risk HPV infection. These results indicate that HPV vaccination of liver transplant candidates and screening for anal HPV infection in high‐risk groups should be considered.     

P16 and human papillomavirus in sinonasal squamous cell carcinoma

Human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (SCC) is a well‐known cause and prognostic indicator, and the utility of p16 as a surrogate marker for HPV status has been established. P16 and its relationship with HPV have not been defined in sinonasal malignancy nor has a link with outcomes been established. Patients with sinonasal SCC from 2011 to 2017 were identified from our pathology database. P16 immunohistochemistry and HPV RNA in situ hybridization were performed on tissue specimens. Forty‐seven patients were included. Disease‐free survival for p16+ patients was significantly higher than p16? patients (P = .043). Fewer HPV+ patients died (P = .052) or experienced recurrence (P = .0437). Odds ratio between p16 and HPV status was 14.19 (95% CI: 1.72, 442.03). Our findings demonstrate improved survival in both the p16+ and HPV+ groups and a positive association between p16 and HPV. There may be similar potential for modifying classification for HPV+ sinonasal SCC.     

p16INK4A immunoexpression and HPV in situ hybridization signal patterns: potential markers of high-grade cervical intraepithelial neoplasia

Integration of human papillomavirus (HPV) into the cell genome is considered to be an important event in the progression of cervical neoplasia. p16, also a useful biomarker of cervical intraepithelial neoplasia (CIN), shows increased immunoexpression with worsening grades of CIN. This study examines the correlation between p16 immunoexpression, grade of CIN, HPV type, and HPV in situ hybridization diffuse and punctate signal patterns (linked to episomal and integrated viral particles, respectively) in 44 cervical biopsies/LEEP excisions classified as CIN 1 and CIN 2/3. In 22 of 25 (88%) CIN 1 lesions, p16 immunoexpression was confined to the lower half of the epithelium, with sporadic to focal staining in 11 of 25 cases (44%). In CIN 2/3 lesions, 15 of 17 (88.2%) showed diffuse, two-thirds to full-thickness staining of the epithelium. High-risk HPV types were found in 20 (80%) CIN 1 lesions and 17 (100%) CIN 2/3 lesions. Punctate signals were detected in only 3 (13.6%) of high-risk HPV-positive CIN 1 lesions and in 17 of 17 (100%) CIN 2/3 lesions (P<0.001). p16 immunoexpression and the presence of punctate signal on HPV in situ hybridization correlated with the degree of cervical neoplasia (P<0.001). However, 3 cases of CIN 1 demonstrating punctate signals did not demonstrate a comparable CIN 2/3 p16 staining pattern. Similarly, two CIN 1 lesions with comparable CIN 2/3 p16 staining showed no evidence of viral integration. Both increased p16 immunoexpression and punctate signal correlate with CIN 2/3 grade, supporting the use of either, or both, tests to confirm CIN 2/3. Strong p16 immunostaining in CIN 1 appears independent of HPV punctate signal type.