Prevalence of human papillomavirus DNA and p16INK4a in penile cancer and penile intraepithelial neoplasia: a systematic review and meta-analysis.

BACKGROUND: Although previous meta-analyses have examined human papillomavirus (HPV) DNA prevalence in penile cancer, none, to our knowledge, have assessed pooled HPV DNA prevalence in penile intraepithelial neoplasia or p16INK4a percent positivity in penile cancer and penile intraepithelial neoplasia. Therefore, we aimed to examine the prevalence of HPV DNA and p16INK4a positivity in penile cancer and penile intraepithelial neoplasia worldwide. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library until July 24, 2017, for English-language articles published from Jan 1, 1986, onwards reporting the prevalence of HPV DNA and p16INK4a positivity, either alone or in combination, in at least five cases of penile cancer or penile intraepithelial neoplasia. Only studies that used PCR or hybrid capture for the detection of HPV DNA and immunohistochemical staining or methylation for the detection of p16INK4a were included. Data were extracted and subsequently crosschecked, and inconsistencies were discussed to reach consensus. Using random-effects models, we estimated the pooled prevalence and 95% CI of HPV DNA and p16INK4a positivity in penile cancer and penile intraepithelial neoplasia, stratifying by histological subtype and HPV DNA or p16INK4a detection method. Type-specific prevalence of HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, and HPV45 in penile cancer was estimated. FINDINGS: Our searches identified 1836 non-duplicate records, of which 73 relevant papers (71 studies) were found to be eligible. The pooled HPV DNA prevalence in penile cancer (52 studies; n=4199) was 50·8% (95% CI 44·8-56·7; I2=92·6%, pheterogeneity<0·0001). A high pooled HPV DNA prevalence was seen in basaloid squamous cell carcinomas (84·0%, 95% CI 71·0-93·6; I2=48·0%, pheterogeneity=0·0197) and in warty-basaloid carcinoma (75·7%, 70·1-81·0; I2=0%, pheterogeneity=0·52). The predominant oncogenic HPV type in penile cancer was HPV16 (68·3%, 95% CI 58·9-77·1), followed by HPV6 (8·1%, 4·0-13·7) and HPV18 (6·9%, 2·9-12·4). The pooled HPV DNA prevalence in penile intraepithelial neoplasia (19 studies; n=445) was 79·8% (95% CI 69·3-88·6; I2=83·2%, pheterogeneity<0·0001). The pooled p16INK4a percent positivity in penile cancer (24 studies; n=2295) was 41·6% (95% CI 36·2-47·0; I2=80·6%, pheterogeneity<0·0001), with a high pooled p16INK4a percent positivity in HPV-related squamous cell carcinoma (85·8%, 95% CI 72·1-95·4; I2=56·4%, pheterogeneity=0·0011) as compared with non-HPV-related squamous cell carcinoma (17·1%, 7·9-29·1; I2=78·3%, pheterogeneity<0·0001). Moreover, among HPV-positive cases of penile cancer, the p16INK4a percent positivity was 79·6% (95% CI 65·7-90·7; I2=89·9%, pheterogeneity<0·0001), compared with 18·5% (9·6-29·6; I2=89·3%, pheterogeneity<0·0001) in HPV-negative penile cancers. The pooled p16INK4a percent positivity in penile intraepithelial neoplasia (six studies; n=167) was 49·5% (95% CI 18·6-80·7). INTERPRETATION: A large proportion of penile cancers and penile intraepithelial neoplasias are associated with infection with HPV DNA (predominantly HPV16), emphasising the possible benefits of HPV vaccination in men and boys. FUNDING: None.

Human papillomavirus and p16 in squamous cell carcinoma and intraepithelial neoplasia of the vagina.

We estimated the overall and type-specific prevalence of human papillomavirus (HPV) and p16 overexpression in vaginal cancer and vaginal intraepithelial neoplasia (VaIN). We conducted a systematic search of PubMed, Embase and Cochrane Library to identify studies published between 1986 and 2017 using PCR-based or Hybrid Capture 2 tests to evaluate the presence of HPV DNA and/or using any method to detect p16 overexpression in VaIN, vaginal squamous cell carcinoma (VaSCC), or other types of vaginal cancer. Applying a random effects model, we estimated the pooled prevalence of HPV and p16 overexpression along with 95% confidence intervals (CIs). The I2 statistic was used to assess heterogeneity. We included 26 studies, reporting HPV prevalence and six studies evaluating p16 overexpression. The pooled HPV prevalences in VaSCC (n = 593) and VaIN (n = 1,374) were 66.7% (95% CI = 54.7-77.8) and 85.2% (95% CI = 78.2-91.0), respectively. Substantial inter-study heterogeneity was observed, and analyses stratified on geographic region, type of tissue, HPV detection method or PCR primer type did not fully explain the observed heterogeneity. The most predominant HPV type among the HPV positive VaSCC and VaIN cases was HPV16, followed by HPV33, and HPV45 (in VaIN) and HPV18, and HPV33 (in VaSCC). In pooled analyses, 89.9% (95% CI = 81.7-94.6) of HPV positive and 38.9% (95% CI = 0.9-90.0) of HPV negative vaginal cancers were positive for p16 overexpression. Our findings suggest that vaccination against HPV might prevent a substantial proportion of vaginal neoplasia and highlight the need for further studies of the possible clinical value of p16 testing in these patients.

Prevalence and type distribution of human papillomavirus in squamous cell carcinoma and intraepithelial neoplasia of the vulva.

In this updated systematic review and meta-analysis, we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN). PubMed, Embase and Cochrane Library databases were used to identify studies published between 1990 and 2015 and using a PCR-based or hybrid capture test to evaluate the presence of HPV DNA in vulvar cancer or VIN. Pooled estimates of the HPV prevalence with corresponding 95% confidence intervals (CI) were calculated based on a random effects model. The I2 statistic was used to describe the amount of heterogeneity. In meta-regression analyses, potential sources of heterogeneity were evaluated. We identified 92 eligible papers, comprising altogether 5,015 cases of vulvar cancer (64 papers) and 2,764 cases of VIN (48 papers). The pooled prevalence of HPV in vulvar cancer was 39.7% (95% CI: 35.1-44.4%). Overall, 76.3% (95% CI: 70.1-82.1%) of VIN lesions tested HPV-positive, while the HPV prevalence in new subcategories of VIN, uVIN and dVIN, was 86.2% (95% CI: 73.5-95.5%) and 2.0% (95% CI: 0-10.0%), respectively. Substantial between-study heterogeneity was observed (vulvar cancer: I2 = 88.4%; VIN: I2 = 90.7%) with the largest variation between geographical regions. Among HPV-positive cases, the predominant high-risk HPV type was HPV16, followed by HPV33 and HPV18. HPV6 was detected as a single infection in a small subset of VIN and vulvar cancer samples. Thus, HPV vaccination targeting these HPV types may prevent a substantial number of vulvar lesions.

Double positivity for HPV DNA/p16 in tonsillar and base of tongue cancer improves prognostication: Insights from a large population-based study.

The aim was to explore the overall survival (OS) for palatine tonsillar squamous cell carcinoma (TSCC), subdivided, according to certainty of tonsillar tumour origin, into specified tonsillar squamous cell carcinomas (STSCCs) and nonspecified tonsillar squamous cell carcinomas (NSTSCCs), and base of tongue squamous cell carcinoma (BSCC) when stratifying for HPV DNA status, p16 expression and combined HPV/p16 status. We included all patients (n = 797) diagnosed with TSCCs and BSCCs in Eastern Denmark as registered in the Danish Head and Neck Cancer Group (DAHANCA) database and the Danish Pathology Databank, 2000-2010. Patients were treated according to national guidelines (radiotherapy +/- concomitant cisplatin). All specimens were analysed using HPV DNA PCR and p16 immunohistochemistry. Clinical information was retrieved from the DAHANCA database and the Danish National Patient Registry. Information on vital status was obtained from the Danish Civil Registration System. We observed improved OS for HPV+/p16+ BSCCs compared to HPV-/p16- (hazard ratio for death [HR], 0.15; 95% CI, 0.09-0.24). Among STSCCs, HPV+/p16+ showed the lowest HR (0.19, 95% CI, 0.13-0.29); whereas, HPV-/p16+ showed an intermediate HR (0.39; 95% CI, 0.22-0.70). For NSTSCCs, HPV+/p16+ and HPV-/p16+ showed similar OS (HRs, 0.39; 95% CI, 0.26-0.59; and 0.48; 95% CI, 0.24-0.95, respectively). Combined HPV+/p16+ was a significantly better prognostic marker in BSCCs and STSCCs than HPV DNA and p16, alone (all p-values < 0.05). Whereas, combined testing in NSTSCC was not better than p16 (p = 0.53), alone. In conclusion, double positivity for HPV/p16 in conjunction with the certainty of tumour site improved prognosis.

A high and increasing HPV prevalence in tonsillar cancers in Eastern Denmark, 2000-2010: the largest registry-based study to date.

The aim was to explore whether the incidence of tonsillar squamous cell carcinomas (TSCCs) increased in Eastern Denmark, 2000-2010, and whether human papillomavirus (HPV) could explain the increase, and to assess the association of HPV prevalence with gender, age, and origin (i.e., the certainty of tonsillar tumor origin). We applied HPV DNA PCR and p16 immunohistochemistry to all TSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and in the Danish Pathology Data Bank (n = 632). Pathologists reviewed and subdivided the tumors into two groups: specified and nonspecified TSCCs. Approximately 10% of HPV-positive tumors was genotyped by amplicon next-generation sequencing. The overall crude incidence of TSCCs increased significantly (2.7% per year) and was explained by an increasing incidence of HPV-positive TSCCs (4.9% per year). The overall HPV prevalence was 58%, with HPV16 being the predominant HPV type. In multivariate analysis, the HPV prevalence was associated with age (<55 vs. >60 years) (OR, 1.72; 95% CI 1.13-2.63) and origin (nonspecified vs. specified TSCCs) (OR, 0.15; 95% CI 0.11-0.22). The association of HPV prevalence with origin increased over time in specified TSCCs (OR per year, 1.10; 95% CI 1.01-1.19), whereas no change over time was observed among nonspecified TSCCs (OR per year, 0.99; 95% CI 0.90-1.08). In conclusion, the observed increase in the number of HPV-positive TSCCs can explain the increasing number of TSCCs in Eastern Denmark, 2000-2010. HPV prevalence was associated with younger age (<55 years) and a high certainty of tonsillar tumor origin.

Chlamydia trachomatis and risk of cervical intraepithelial neoplasia grade 3 or worse in women with persistent human papillomavirus infection: a cohort study.

OBJECTIVES: Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in women with prevalent HPV infection and in a subgroup of women with persistent HPV infection. METHODS: Participants in this population-based cohort study underwent a structured interview, including history of CT infection, and subsequently cervical exfoliated cells were obtained for HPV DNA and CT DNA testing. Women with high-risk HPV DNA infection and no prevalent cervical disease constituted the overall study population (n=1390). A subgroup of women with persistent HPV infection (n=320) was also identified. All women were passively followed for development of cervical lesions in the national Pathology Data Bank. HRs and 95% CIs for CIN3+ during follow-up (up to 19 years) were estimated in an accelerated failure time model. RESULTS: Women who reported more than one CT infection had a statistically significantly increased risk of CIN3+ (high-risk HPV-positive, HR=2.51, 95% CI 1.44 to 4.37) (persistent HPV infection, HR=3.65, 95% CI 1.53 to 8.70). We found no association between CT DNA and subsequent risk of CIN3+ among women who were HPV-positive or had a persistent HPV infection at baseline. CONCLUSIONS: Repeated CT infections increased the risk of CIN3+ among women with prevalent as well as persistent high-risk HPV infection.

Prevalence of Human Papillomavirus in endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer. METHODS: We conducted a systematic review and meta-analysis to investigate the pooled prevalence of HPV DNA in endometrial cancer. Using meta-regression, we further analyzed whether factors such as geographical region, HPV DNA detection method, publication year and tissue type were associated with HPV prevalence. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for studies providing data on HPV prevalence in cases with endometrial cancer and in controls with normal or hyperplastic endometrial tissue. RESULTS: We identified 28 papers (29 studies) examining the prevalence of HPV DNA in tumor tissue from endometrial cancer comprising altogether 1026 cases of endometrial cancer. The HPV prevalence varied considerably from 0% to 61.1%. From the random effects meta-analysis, the pooled prevalence of HPV DNA in endometrial cancer was 10.0% (95% CI: 5.2-16.2) with large between-study heterogeneity (I(2)=88.2%, p<0.0001). The meta-regression showed that HPV DNA detection method was statistically significantly associated with HPV prevalence (p=0.0016): the pooled HPV prevalence was 6.0% (95% CI: 1.5-13.0) using general primers, 18.9% (95% CI: 8.6-32.1) using type-specific primers and 1.0% (95% CI: 0.0-3.6) using non-PCR based methods. None of the other a priori defined variables were statistically significantly associated with HPV prevalence. The pooled OR was 1.43 (95% CI: 0.68-3.00) indicating that the odds of HPV was not increased in cases versus controls. CONCLUSIONS: HPV appears to have a limited or no role in the etiology of endometrial cancer.

Prevalence of genital human papillomavirus among men in Europe: systematic review and meta-analysis.

INTRODUCTION: Human papillomavirus (HPV) is the commonest sexually transmitted infection worldwide and causes substantial morbidity in both sexes. Most European countries offer HPV vaccination for girls, but vaccine recommendations for boys are warranted. AIMS: The aims of this study were to investigate the prevalence of genital HPV, identify parameters that affect the prevalence, and describe the type-specific prevalence among men in Europe. METHODS: A systematic review and meta-analysis of the published literature in PubMed and Embase. MAIN OUTCOME MEASURES: Genital HPV prevalence and factors influencing prevalence in general and high-risk male populations in Europe. RESULTS: We included 31 articles that gave the prevalence of genital HPV DNA among men in northern, southern and western Europe; no studies from eastern Europe were identified. The pooled HPV prevalence among 1,863 men representing the general population (nine studies) was 12.4%, with large heterogeneity between studies (I(2) = 96.3%, P < 0.0001). The pooled HPV prevalence among 6,428 men in the high-risk population (22 studies) was 30.9%, also with substantial heterogeneity (I(2) = 95.6%, P < 0.0001). In unadjusted meta-regression analysis, the HPV prevalence in the general population was significantly higher in studies published after 2000 (28.5%) than in earlier studies (8.8%) (P = 0.0179). In the meta-regression analysis adjusted by publication year, the heterogeneity in the two population groups could not be explained by geographical region, anatomical sampling site, or HPV detection method. HPV16 was the most prevalent high-risk type in both populations. CONCLUSIONS: HPV prevalence differs in male general and high-risk populations, but HPV16 and HPV18 are among the most common HPV types detected in both groups. Our findings contribute knowledge that may be useful as a baseline measure before the introduction of HPV vaccination for boys in Europe, and add to understanding of the epidemiology of HPV infection in men.

Prevalence of human papillomavirus in epithelial ovarian cancer tissue. A meta-analysis of observational studies.

OBJECTIVE: The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue. MATERIAL AND METHODS: Observational studies published until 4 March 2013 were identified in PubMed and Embase. We adhered to MOOSE guidelines and included 22 studies (case-control, cross-sectional studies). A pooled estimate of the HPV prevalence with corresponding 95% confidence interval (CI) was calculated based on a random effect model. In a meta-regression analysis we examined the contribution of different factors to heterogeneity. Furthermore, publication bias was evaluated. RESULTS: The pooled HPV prevalence in ovarian cancer tissue was 15.5%, but wide variation was found (0-66.7%). After stratification by geographical region, publication year, tissue type and method of HPV detection, we found that the prevalence of HPV varied most markedly by geographical area, the prevalence being 45.6% (95% CI, 31.0-60.3) in Asia, 18.5% (95% CI, 8.5-28.6) in Eastern Europe, 1.1% (95% CI, -1.6 to 3.8) in Western Europe and zero in North America. A meta-regression analysis revealed that the difference between geographical regions could not be explained by HPV detection method or type of tissue. CONCLUSIONS: Great geographical variation exists in HPV prevalence in ovarian cancer tissue, which is not explained by different HPV detection methods. The results suggest that HPV is unlikely to play an important role in Western European and American women, but cannot reject a role of HPV in other populations.

Celebrating a century of APMIS: a legacy of pathology, microbiology, and immunology.

This manuscript commemorates the 100th anniversary of APMIS, highlighting its evolution from a regional journal, founded in 1924 as Acta Pathologica et Microbiologica Scandinavica, to an international platform fostering global collaboration in pathology, microbiology, and immunology. The journal's inception was driven by Ulrik Quensel's vision in 1919, leading to the establishment of the Northern Pathological Society and the launch of the journal in 1924. APMIS has consistently published landmark research, including significant contributions from prominent. These studies have advanced understanding in fields such as pathology, microbiology, and immunology. The journal expanded its scope in the 1970s to include immunology, rebranding as APMIS in the mid-1980s. Recent decades have seen a continued commitment to cutting-edge research and an increasing impact factor. As APMIS transitions to an Open Access model under Wiley, it will be renamed the PMI Journal (Pathology, Microbiology, and Immunology) to reflect its global reach and dedication to scientific excellence. This centennial celebration acknowledges the contributions of editors, authors, and readers, looking forward to future advancements in biomedical research.

The p53 target Wig-1 regulates p53 mRNA stability through an AU-rich element.

The p53 target gene Wig-1 encodes a double-stranded-RNA-binding zinc finger protein. We show here that Wig-1 binds to p53 mRNA and stabilizes it through an AU-rich element (ARE) in the 3' UTR of the p53 mRNA. This effect is mirrored by enhanced p53 protein levels in both unstressed cells and cells exposed to p53-activating stress agents. Thus, the p53 target Wig-1 is a previously undescribed ARE-regulating protein that acts as a positive feedback regulator of p53, with implications both for the steady-state levels of p53 and for the p53 stress response. Our data reveal a previously undescribed link between the tumor suppressor p53 and posttranscriptional gene regulation via AREs in mRNA.

Differential expression of cellular microRNAs in HPV 11, -16, and -45 transfected cells.

Human papillomaviruses (HPVs) are highly prevalent giving rise to both benign and malignant lesions why they are classified as high- and low-risk viruses. In this study we selected one low-risk (HPV 11) and two high-risk (HPV 16 and -45) types for genomewide miRNA analysis to investigate possible common and distinct features in the expression profiles. For this purpose we developed a cell culture model system in HaCaT cells for expression of the viral genomes under standardized conditions. We identified 25 miRNAs which were differentially regulated in two or three HPV types where 13 miRNAs were in common for all three types. Among the miRNAs identified, miR-125a-5p, miR-129-3p, miR-363, and miR-145 are related to human cancers. Noteworthy, miR-145 is found upregulated in the miRNA profiles of both high-risk HPV types. For selected differentially expressed miRNAs in HPV 16 predicted miRNA target transcript involved in signal transduction, RNA splicing and tumor invasive growth were validated by qRT-PCR. In addition, our results imply that the early 3' untranslated region (3'UTR) of the three HPV genomes were not a target for miRNA regulation.

Differential expression of cellular microRNAs in HPV-11 transfected cells. An analysis by three different array platforms and qRT-PCR.

Human papillomavirus type 11 (HPV-11) infects the genital and the respiratory tract leading to condylomas and respiratory papillomatosis. HPV infections are restricted to epithelial tissue and the progression through the virus lifecycle is tightly coordinated to the differentiation of the host cell. The changes of cellular microRNAs by HPV-11 gene expression were investigated in a cell culture model of HaCaT cells transfected with HPV-11, with the goal of understanding which cellular processes were affected by the virus. Human microRNA profiling was conducted on three different array platform systems and because very few microRNAs (miR-663, -638, -149* and -92b*) were consistently found in all three array data sets we performed extensive statistical analyses of the array data and the qRT-PCR validation. We assume that the most reliable differentially expressed microRNAs are the ones identified by more than one array platform. We also show that TaqMan® qRT-PCR validation is of limited use for less abundant microRNAs.

Differences in transcriptional activity of cutaneous human papillomaviruses.

The interaction between UV-B irradiation and cutaneous human papillomaviruses (HPV) has been suggested to be of relevance for the development of non-melanoma skin cancers. We investigated the activity within the upstream regulatory region (URR) of the HPV types 8, 38, 92, 93 and 96, as well as their responsiveness to UV-B irradiation and cellular differentiation. Promoter activities were higher in HaCaT than in SiHa cells, corresponding to the HPV tissue tropism. Transcriptional start sites were mapped at P(92) (HPV-38), P(45) (HPV-92), P(7439) (HPV-93) and P(256) (HPV-96). Transcription from HPV-8, 93 and 96 URR was up-regulated by cellular differentiation, linking the activity of these HPVs to the cellular state. UV-B irradiation activated HPV-8 but inhibited HPV-38 and HPV-93 whereas HPV-92 and 96 were not affected. As there are variable UV-B responses among the HPV types, further studies of interactions between UV-B and HPV need to consider the HPV type.

Conserved CPEs in the p53 3' untranslated region influence mRNA stability and protein synthesis.

BACKGROUND: The 3' untranslated region (UTR) of p53 mRNA contains two conserved U-rich sequences resembling cytoplasmic polyadenylation elements (CPE). It is not known if these sequences regulate p53 expression by post-transcriptional mechanisms. MATERIALS AND METHODS: Stable p53 3'UTR reporter HaCaT skin and MCF-7 breast cancer cell lines were established. Quantitative PCR and an enzymatic assay were used to quantify the reporter mRNA and protein levels, respectively. Proteins binding to the CPEs were identified by RNA-immunoprecipitation (IP) and quantitative mass spectroscopy. RESULTS: The wild-type p53 3'UTR reduced mRNA steady state levels of the reporter gene and point mutations in the CPEs rescued the mRNA steady state levels in the MCF-7 cells, but not in the HaCaT cells. In both cell lines, the CPEs had a significant effect on translation of the reporter and influenced the effect of UV irradiation. Several proteins (including GAPDH, heterogeneous nuclear ribonucleoprotein (hnRNP) D and A/B) were identified from the MCF-7 cytoplasmic extracts that bound specifically to the CPEs. CONCLUSION: Two conserved CPEs in the p53 3'UTR regulate stability and translation of a reporter mRNA in non-irradiated as well as irradiated cells. GAPDH, hnRNP D and hnRNP A/B bind specifically to the p53 CPEs and could potentially be involved in the post-transcriptional regulation of p53.

Cancer genomics.

Almost all cells in the human body contain a complete copy of the genome with an estimated number of 25,000 genes. The sequences of these genes make up about three percent of the genome and comprise the inherited set of genetic information. The genome also contains information that determines when and where in the organism a given gene is active. This is the epigenetic information. Genomics is the study of DNA sequences and the epigenetic information of gene regulation.

Human papillomavirus and pterygium. Is the virus a risk factor?

BACKGROUND: Pterygium is a disease of unknown origin and pathogenesis that might be vision threatening. It is characterised by a wing-like conjunctival overgrowth of the cornea. Several studies have investigated human papillomavirus (HPV) as a risk factor for the development of pterygia, but the results are inconclusive. AIM: To investigate a large sample of pterygia for the presence of HPV in order to clarify the putative association between pterygia and HPV. METHODS: 100 specimens of pterygium from Danish patients and 20 normal conjunctival biopsy specimens were investigated for the presence of HPV with PCR technique using beta-globin primers to access the quality of the extracted DNA and the HPV primers MY09/11 and GP5+/6+. HPV-positive specimens underwent subsequent HPV typing with type-specific HPV primers and further investigation with DNA in situ hybridisation (ISH). RESULTS: 90 of 100 investigated pterygia proved suitable for HPV analysis by PCR. As beta-globin could not be amplified, 10 specimens were excluded from the study. 4 of 90 pterygia harboured HPV. HPV type 6 was identified in all four HPV-positive pterygia. The 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. All four pterygia that were HPV type 6 positive were DNA ISH negative. CONCLUSIONS: The low presence of HPV DNA in pterygia does not support the hypothesis that HPV is involved in the development of pterygia in Denmark.

Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series.

AIM: To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). METHODS: Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing. RESULTS: HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. CONCLUSION: There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

Correlation between HPV status at T and N sites of oropharyngeal squamous cell carcinomas.

OBJECTIVES: Human papilloma virus (HPV) is known to be associated with oropharyngeal squamous cell carcinomas (OPSCC) and may potentially play a vital role in tumor metastasis. The purpose of this study was to correlate HPV status of cervical lymph node metastases with their respective primary OPSCC tumor. METHODS: Formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from 34 patients with cervical lymph node metastases were analyzed with HPV 16 DNA polymerase chain reaction (PCR), p16 immunohistochemistry and HPV typing. The results were correlated with the HPV status and type found in the primary tumors of OPSCC. RESULTS: Comparing HPV DNA status with p16 we found that 21 primary tumors and lymph node metastases were HPV positive (61.8%) and seven primary tumors and lymph node metastases were HPV negative (20.6%). Six patient samples differed when correlating the primary tumor and lymph node metastasis (17.6%). CONCLUSIONS: In this study, HPV status in OPSCCs and their cervical lymph node metastases correlated in the vast majority of cases. However, HPV detection methods may have certain limitations resulting in varying degree of non-correlation. This should be taken into account when stratifying treatment in regard to HPV status.