Evidence Of Human Papillomavirus Research Articles

Abstract 363: Investigating the potential clinical predictive value of virus genotype, menopausal status and mutational landscape in cervical cancer tissue using a NGS based human papillomavirus (HPV) assay and whole exome sequencing (WES)

Abstract Purpose: Persistent HPV infections are associated with nearly all cervical cancers and some head & neck and genitourinary cancers. In cervical cancer, 14 high risk HPV genotypes have been previously identified with varying geographical prevalence and carcinogenicity. HPV16 and 18 account for >70% of cervical cancer incidence worldwide. There is an unmet need to explore HPV-associated cancer pathology, HPV infection status and molecular profiles to detect virus load and identify predictive gene signatures. We investigated the association between HPV genotypes and clinicopathological features and analyzed the mutational landscape using the ImmunoID NeXT Platform®. Methods: Early stage cervical cancer FFPE tissue samples (n=38) were analyzed. We detected and quantified oncoviral DNA, identified likely somatic mutations, and quantified genome-wide mutational burden. Any sample with at least one filtered read of HPV evidence was considered positive; zero such evidential reads were reported across a negative control cohort of > 439 non-cervical cancer samples. Oncovirus DNA counts and HPV genotype status were then evaluated against covariates (age; menopausal status) for statistical significance. Finally, mutation frequency was assessed in genes comprising major cervical cancer driver pathways from the KEGG and Biocarta databases. Results: Oncoviral HPV infections were detected using a NGS based approach in all tumor tissue with demonstrated robust assay performance. A statistically significant difference in viral DNA counts was observed between high risk genotypes HPV16 and 18 (n=27) and all other genotypes (n=10), (p=0.028, Student's t). Genotypes were also significantly associated with menopausal status (p=0.01, Fisher's Exact Test) and age at surgical resection (p=0.011, Student's t). Among the pathways considered, TGF-β and MAP-kinase were the most frequently mutated across 38 samples and multiple pathway annotations. Conclusions: We applied a powerful NGS based WES approach that enables accurate detection of HPV genotypes with quantification of HPV viral DNA. This quantitative approach represents a possible promising clinical benefit over existing qualitative HPV genotyping assays and may have the potential for further development to define cancer type and treatment specific cutoff values for cancer prognosis. Furthermore, our results demonstrate that a WES based approach provides clinically valuable insights into the constitutive molecular mechanisms of cervical cancer. The association of HPV genotypes with clinical patient characteristics and/or mutational profiles has the potential to identify prognostic and predictive clinical biomarkers and to provide critical information for treatment defining strategies. Citation Format: Jean-Christophe Pignon, Heidi Giese, Dorothee Foernzler, Lee D. McDaniel, Gabor Bartha, Juergen Scheuenpflug, Zheng Feng. Investigating the potential clinical predictive value of virus genotype, menopausal status and mutational landscape in cervical cancer tissue using a NGS based human papillomavirus (HPV) assay and whole exome sequencing (WES) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 363.

SPECTRUM OF ORAL PREMALIGNANT AND MALIGNANT LESIONS IN FANCONI ANEMIA PATIENTS: DIAGNOSTIC AND MANAGEMENT CHALLENGES

Background Fanconi anemia (FA) is characterized by congenital anomalies, progressive bone marrow failure, and increased cancer risk. FA patients have a >300-fold increased risk of developing head and neck cancers, including oral squamous cell carcinoma (OSCC). Objective To describe the spectrum of premalignant/malignant oral lesions illustrating diagnostic and management challenges in patients with FA. Methods Five patients with FA seen regularly were selected. Oral lesions and management strategies were systematically documented over time. Results All 5 patients with FA (4 male; 1 female; median age 21) developed oral lesions without evidence of human papilloma virus or typical risk factors for OSCC. All patients had received previous hematopoietic cell transplantation. Three patients developed OSCC of the lateral tongue (n = 2) and gingiva (n = 1), preceded by rapidly progressing premalignant epithelial dysplasia. All 3 had previous history of graft-vs-host disease, a known risk factor in patients with FA. Patients with OSCC developed recurrent/new dysplastic lesions within 4 years following management of OSCC. The 2 patients with no OSCC showed premalignant epithelial dysplasia and verrucous hyperkeratosis of the tongue and palatal gingiva, respectively. One patient with OSCC also developed pharyngeal wall SCC and 2 separate basal cell carcinomas of the upper lip. Our current management strategies include frequent evaluation (monthly to every 3-6 months) with low tolerance and recommendation for biopsy of suspicious lesions. Conclusions Patients with FA develop premalignant lesions and OSCC at a younger age and higher rate than non-FA patients and require screening examinations for such lesions at least every 6 months. Lower biopsy thresholds and histologic evaluation are recommended. Fanconi anemia (FA) is characterized by congenital anomalies, progressive bone marrow failure, and increased cancer risk. FA patients have a >300-fold increased risk of developing head and neck cancers, including oral squamous cell carcinoma (OSCC). To describe the spectrum of premalignant/malignant oral lesions illustrating diagnostic and management challenges in patients with FA. Five patients with FA seen regularly were selected. Oral lesions and management strategies were systematically documented over time. All 5 patients with FA (4 male; 1 female; median age 21) developed oral lesions without evidence of human papilloma virus or typical risk factors for OSCC. All patients had received previous hematopoietic cell transplantation. Three patients developed OSCC of the lateral tongue (n = 2) and gingiva (n = 1), preceded by rapidly progressing premalignant epithelial dysplasia. All 3 had previous history of graft-vs-host disease, a known risk factor in patients with FA. Patients with OSCC developed recurrent/new dysplastic lesions within 4 years following management of OSCC. The 2 patients with no OSCC showed premalignant epithelial dysplasia and verrucous hyperkeratosis of the tongue and palatal gingiva, respectively. One patient with OSCC also developed pharyngeal wall SCC and 2 separate basal cell carcinomas of the upper lip. Our current management strategies include frequent evaluation (monthly to every 3-6 months) with low tolerance and recommendation for biopsy of suspicious lesions. Patients with FA develop premalignant lesions and OSCC at a younger age and higher rate than non-FA patients and require screening examinations for such lesions at least every 6 months. Lower biopsy thresholds and histologic evaluation are recommended.

Human papillomavirus (HPV) types among Alaska native women attending a colposcopy clinic in Anchorage, Alaska, 2009\u20132011

BackgroundThe first HPV vaccines licensed targeted two HPV types responsible for most cervical cancers. A 9-valent vaccine (9vHPV), targeting 5 additional types, was introduced in 2016 and is currently the only HPV vaccine available in the United States. Previous studies demonstrated high rates of HPV infection in Alaska Native (AN) women. We sought to measure prevalence of high risk HPV types in AN women undergoing colposcopy and to determine those preventable by vaccination.MethodsFor this cross-sectional study, we recruited women who were undergoing colposcopy for clinical indications at Alaska Native Medical Center to obtain cervical brush biopsy samples. Specimens were shipped to Atlanta, Georgia for DNA extraction, HPV detection, and typing using L1 PCR with type-specific hybridization to detect 37 HPV types.ResultsFour hundred eighty eight specimens from 489 women were tested. At least one HPV type was found in 458 (94%) specimens. Of 458 participants who were HPV positive, 332 (72%) had two or more types. At least one type targeted by 9vHPV was detected in 95% of participants with CIN 3 (21/22), 82% with CIN 2 (37/45), and 65% with CIN 1 (119/184). (p < 0.001) HPV 16 or 18 were detected in 77% (17/22) with CIN 3, 53% (24/45) with CIN 2, and 36% (67/184) with CIN 1. (p < 0.001).ConclusionsA substantial proportion of AN women attending colposcopy clinic had evidence of HPV 16/18 infection, as well as other high risk types targeted by 9vHPV. At least one 9vHPV type was detected in 62% of the participants overall, and 95% of participants with CIN3. AN women are expected to benefit from vaccination against HPV 16/18, and will have greater benefit from 9vHPV. Information from this study could be used to develop public health strategies to increase vaccine uptake, or to track HPV genotype prevalence over time.

Absence of Human Papillomavirus in Benign and Malignant Breast Tissue.

Background & Objective:Malignant breast tumors, which are one of the most important deadly cancers in women, like many other cancers, are proposed to be related to viruses etiologically. Proper management of breast carcinoma necessitates an identification of the etiological factors. Human Papillomavirus is considered to have an etiological role in breast carcinoma. We carried out this study to find out if Human Papillomavirus-DNA is present in the malignant and benign breast tissue in our patients. Methods:Seventy-five paraffin-embedded breast cancer tissues and 75 normal breast tissues and benign breast lesions were examined in this study (case-control) to look for Human Papillomavirus-DNA employing Nested Polymerase Chain reaction. The tissues were examined over a period of ten years in the pathology department of the Pathobiology Laboratory Center of Tehran.Results:No Human Papillomavirus-DNA was found in any of the malignant or control group specimens.Conclusion:Our results showed no evidence of Human Papillomavirus in cancerous and benign tissues, which is consistent with some other studies in English medical literature. More investigations using more specimens from different parts of the country are required to confirm the presence or absence of any connection between Human Papillomavirus and development of breast carcinoma in Iran.

Novel synchronous nasal involvement of inverted papilloma and recurrent respiratory papillomatosis with confirmed human papillomavirus isolated from nasal septum and middle turbinate: a case report

BackgroundRecurrent respiratory papillomatosis is a chronic disease of viral origin affecting the larynx, trachea, and lower airways. Inverted papilloma, most commonly originating from the lateral nasal wall, is typically a single, expansile, locally aggressive tumor that remodels bone around the site of origin.Case presentationWe report a case of histopathologically proven inverted papilloma occurring in a 50-year-old Caucasian man with recurrent respiratory papillomatosis affecting his nasal cavity, larynx, and trachea. This constitutes the first report of nasal involvement in recurrent respiratory papillomatosis. Viral in situ hybridization studies demonstrated evidence of human papillomavirus in both the septum and middle turbinate subsites. Repeat nasal excision with margin analysis is planned.ConclusionsThis report emphasizes the importance of considering a broad differential diagnosis in patients with papillomata, and obtaining comprehensive histopathologic evaluation of lesions in multiple subsites in order to rule out inverted papilloma or overt malignant transformation, particularly if high-risk human papillomavirus (HPV) subtypes are identified.Level of evidence4

Effectiveness of cold coagulation in treating high-grade cervical intraepithelial neoplasia: the human papillomavirus evidence of cure

We retrospectively analysed post-treatment human papillomavirus (HPV) results in women treated for cervical intraepithelial neoplasia (CIN) to establish if ‘virological cure’ rates achieved by cold coagulation matched those for large-loop excision of the transformation zone (LLETZ) in the treatment of CIN. The main outcome measure was the rate of non-detection of HPV at 6- and 18-month follow-up. HPV was not detected in 82.0% and 86.0% of women at 6- and 18-month follow-up, respectively. In women with high-grade CIN (CIN 2 or worse), there was no difference in HPV non-detection rates among the two treatment methods at six-month (81.8% for cold coagulation vs. 84.0% for LLETZ, χ2=0.23, p value=.632), and 18-month follow-up (83.3% for cold coagulation vs. 89.2% for LLETZ, χ2=1.46, p value=.227). Cervical cold coagulation provides a high ‘virological cure’ rate for all grades of CIN, equivalent to that seen with LLETZ.Impact StatementWhat is already known on this subject? It is well established that CIN cure rates after treatment with cold coagulation are comparable to those of excisional methods and are over 90% on cytological follow-up post-treatment. Furthermore, there are no demonstrable adverse effects on fertility and delivery in pregnancies conceived after cold coagulation according to long-term follow-up studies. In contrast, there is a positive correlation between treatment with LLETZ and the risk of subsequent subfertility and adverse pregnancy outcomes.What the results of this study add? This study provides evidence that cold coagulation achieves similar cure rates to that of LLETZ not only in cytology but also in HPV test of cure. This finding is significant as we are moving to a primary HPV cervical screening programme.What the implications are of these findings for clinical practice and/or further research? A negative high-risk HPV test provides a greater reassurance of a low risk of CIN 3 or cancer than a negative cytology result. Therefore, given parity to LLETZ in ‘virological cure’ rate and having no known adverse effects on fertility and pregnancy, cold coagulation should be used to treat most cases of CIN, especially in women of reproductive age.

No evidence for human papillomavirus having a causal role in salivary gland tumors

BackgroundSalivary gland malignancies are a very heterogeneous group of cancers, with histologically > 20 different subtypes, and prognosis varies greatly. Their etiology is unknown, however, a few small studies show presence of human papillomavirus (HPV) in some subtypes, although the evidence for HPV having a causal role is weak. The aim of this study was to investigate if HPV plays a causal role in the development of different parotid salivary gland tumor subtypes.MethodsDNA was extracted from 107 parotid salivary gland formalin fixed paraffin embedded tumors and 10 corresponding metastases, and tested for 27 different HPV types using a multiplex bead based assay. HPV DNA positive tumors were stained for p16INK4a overexpression by immunohistochemistry.ResultsOne of the 107 malignant parotid salivary gland tumors (0.93%) and its corresponding metastasis on the neck were positive for HPV16 DNA, and both also overexpressed p16INK4a. The HPV positive primary tumor was a squamous cell carcinoma; neither mucoepidermoid nor adenoid cystic tumors were found HPV positive.ConclusionsIn conclusion, HPV DNA analysis in a large number of malignant parotid salivary gland tumors, including 12 different subtypes, did not show any strong indications that tested HPV types have a causal role in the studied salivary gland tumor types.

Investigation of the presence of HPV related oropharyngeal and oral tongue squamous cell carcinoma in Mozambique

BackgroundCervical cancer caused by the human papillomavirus (HPV) is endemic in East Africa. Recent, dramatic, increases in the incidence of oropharyngeal cancer in the United States and Europe are linked to the same high risk HPV genotypes responsible for cervical cancer. Currently, there is extremely limited data regarding the role of HPV in head and neck cancers in Africa. Evidence of HPV as an etiologic agent in head and neck cancers in Africa would have important prevention and treatment implications. MethodsA retrospective single institution review of oral tongue and oropharyngeal squamous cell carcinomas diagnosed between 2005 and 2013 was performed. Individual case data for 51 patients with biopsy proven squamous cell carcinoma (SCC) from the oropharynx (n=22) and oral tongue (n=29) were identified. Formalin fixed, paraffin embedded biopsy samples were obtained and evaluated for p16 by immunohistochemistry and HPV genotype 16 specific oncogenes, E6 and E7, by PCR. ResultsAll of the positive controls, but none of the oropharyngeal samples stained positively for p16. Two of the oral tongue samples stained positive for p16. None of the oropharyngeal or oral tongue cases demonstrated PCR products for HPV-16 E6 or E7. ConclusionsThough Mozambique has extremely high levels of HPV positive cervical cancer this study demonstrates an absence of HPV positive oropharyngeal or oral tongue squamous cell carcinoma within biopsy samples from a single referral hospital in Maputo, the capital of Mozambique.

Primary squamous cell carcinoma of the stomach: A case report.

Pure squamous cell carcinoma (SCC) of the stomach is rare and resembles SCC arising elsewhere in the body. The pathogenesis of SCC remains unclear and controversial. At present, <100 cases of primary SCC of the stomach have been reported. The current study presents a case of SCC of the stomach in a 61-year-old male. Total gastrectomy was performed and a 7.0×6.7×4.5-cm tumor with a superiorly located ulcer was identified in the cardia. Upon histological examination, a moderately-differentiated SCC was observed. Tumor cells extended to the serosa, and the perigastric regional lymph node was also involved. No evidence of human papillomavirus (HPV) or Epstein-Barr virus (EBV) infection was identified using a DNA microarray and in situ hybridization, respectively. A post-operative computed tomography scan four months after the gastrectomy revealed tumor recurrence and dissemination of the tumor to the jejunum and pancreas. The patient succumbed to the disease six months later despite the administration of low-dose adjuvant 5-fluorouracil/cisplatin chemotherapy.

Screening for Cervical Cancer: A Review of Outcome among Infertile Women in a Tertiary Hospital in North-West Nigeria.

Background:Cervical cancer is the most common genital tract malignancy in the developing countries of the world. Interestingly, it has a pre-invasive stage, which can be detected through screening. The etiological organism of the disease is the human papilloma virus (HPV) that is sexually transmitted and sexually transmitted infections play a major role in the causation of infertility in developing countries.Aim:The aim of this study is to determine the prevalence of abnormal cervical smear among infertile women at Usmanu Dan-Fodiyo University Teaching Hospital (UDUTH) Sokoto, Nigeria.Materials and Methods:This is a cross-sectional study involving the assessment of cervical smears taken from infertile women attending the gynecological out-patient clinic of UDUTH sokoto over a 12-month period. cross-sectional study involving the assessment of the cervical smears taken from infertile women attending the gynecological out-patient clinic of UDUTH Sokoto over a 12-month period. Statistical analysis of the results was carried out using the EPI-INFO 3.5.1 (CDC, Atlanta Georgia, USA). Chi square test was used for association at p-value< 0.05 at 95 % confidence intervalResults:A total of 162 patients were screened during the study period. Their ages ranged from 15 to 46 years with a mean of 27.9 (6.2) years and modal age of 25-34 years. Majority of the subjects 88/159 (55.4%) were in the lower socio-economic class and 75/159 (47.2%) of the women were nullipara. Out of the 159 subjects with adequate smears, 58/159 (36.8%) were normal while 44/159 (27.8%) had inflammatory lesions. Cervical intraepithelial lesions were observed in 18/159 (11.3%) of the smears while 25 (15.7%) had evidence of HPV infection.Conclusions:Considering the relatively high incidence 18/159 (11.3%) of cervical intraepithelial lesions seen among the subjects, there is the need to integrate cervical smear in the general infertility work-up.

No Evidence of Human Papillomavirus in Patients with Breast Cancer in Hong Kong, Southern China

Several studies have suggested that viral oncogenesis is one of the etiologic factors of breast cancer, while others are provocative, however, their association remains controversial. The purpose of this study was to investigate whether the human papillomavirus (HPV) DNA is present in the blood and tissue samples of breast cancer patients in Hong Kong. A total of 102 patients with breast tumour tissues and adjacent normal tissues were available and recruited unselectively. Both DNA and RNA were extracted from those samples, and real-time quantitative PCR was performed to detect HPV-16, with 18 sequences targeting the E6 and L1 regions. Results showed that HPV DNA sequences were absent in all the blood and breast tissues. These data argue against the role of oncogenic HPV in the pathogenesis of breast cancer. Additional lines of evidence need to be obtained in order to assess the possibility of breast cancer prevention using HPV vaccines.

Abstract 4785: A pilot study of the association and prevalence of the human papillomavirus (HPV) in non-small cell lung cancer (NSCLC).

Abstract Introduction: Given its potent oncogenic properties, the prevalence of HPV, and the proximity of the bronchial epithelia to the oral cavity we hypothesized that HPV infection may have a role in the causality of NSCLC in patients without a significant smoking history. In Asia, studies report rates of HPV infection in NSCLC tumors as high as 80%. The expression of p16 in head and neck cancer is a reliable surrogate for HPV, and its presence portends a good prognosis. The goal of our study was to analyze archival lung tissue for the presence of p16 expression and HPV infection among never smokers or &amp;lt; 10 pack year smoking patients with NSCLC. Methods: Surgical specimens from never/light smokers was identified in the Fox Chase Cancer Center Biosample Repository. A tissue microarray was constructed for immunohistochemistry analysis on the quantitative platform, AQUA, for p16. DNA was also extracted from archival tissue for assessment of p16 status. Real-time PCR and reverse hybridization (INNO-LiPA) was utilized to detect evidence of HPV genes in tumor samples. In order to determine if the viral genome was episomal or integrated, PCR to determine E2:E6 ratios were employed. The association of p16 expression and HPV infection was assessed. Study results: Available tissue included 36 NSCLC surgical specimens from never/light smokers (1995-2009). Patient characteristics were: 28 female, age range: 47-84, Histology: adenocarcinoma (31, 86%), adenosquamous (3, 8%), and squamous (2, 6%). TNM Stage: T1 (5, 14%), T2 (27, 75%), T3 (1, 3%), T4 (1, 3%), N0 (18, 50%), N1 (8, 22%), N2 (8, 22%), N3 (1, 3%), M1 (2, 5.5%). The p16 AQUA score range: 91-7733. A natural cut point occurred at 3000 with 25 low (p16-) and 8 high (p16+) expressers. AQUA score correlated with standard IHC H score (p=0.0005). There was no significant relationship between p16 level and gender, T or N stage. p16+ was associated with a trend towards inferior survival (HR 2.18, p=0.157). Evidence of HPV 16 and 18 viral DNA, as measured by real-time PCR and reverse hybridization (INNO-LiPA) was detected in 4 samples; 16 (2, 5.5%), 18 (2, 5.5%). Additional high risk oncogenic HPV viruses which were also detected included HPV 35, 52 and 53. Based on the calculation of HPV 16 E2:E6 ratios, both specimens (1 male, 1 female) with evidence of HPV16 infection also had evidence of genome integration of HPV16 DNA. There was no association between HPV infection and p16 expression. Conclusions: In our series of NSCLC among never or light smokers, the rate of HPV 16 viral infection and integration was 5.5%. Notably, all HPV 16 infected tumors had integrated genomes; a novel finding among NSCLC tumors in the Western population. In our small series, p16+ status was not associated with HPV infection. Future study of the potential role of HPV in the pathogenesis of NSCLC warrants exploration, including an assessment of genomic integration of additional strains of high risk HPV DNA. Citation Format: Ranee Mehra, Brian Egleston, Donghua Yang, Walter Scott, Hossein Borghaei, Camille Ragin. A pilot study of the association and prevalence of the human papillomavirus (HPV) in non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4785. doi:10.1158/1538-7445.AM2013-4785

Detection of human papilloma virus and p16 expression in high-grade adenoid cystic carcinoma of the head and neck

Squamous cell carcinoma of the head and neck, particularly basaloid squamous cell carcinoma, may be difficult to distinguish from high-grade adenoid cystic carcinoma. Evidence of human papilloma virus (HPV) infection, particularly HPV 16, is frequently found in non-keratinizing oropharyngeal squamous cell carcinoma. Immunoreactivity for p16, a surrogate marker for HPV infection, often parallels the HPV infection status in oropharyngeal squamous cell carcinoma. However, the incidence and correlation between p16 expression and HPV infection in high-grade adenoid cystic carcinoma is unknown. Sixteen cases of high-grade adenoid cystic carcinoma, three cases of dedifferentiated adenoid cystic carcinoma and eight cases of low-/intermediate-grade adenoid cystic carcinoma were identified for inclusion in the study. All cases were tested by immunohistochemistry for p16 expression and in situ hybridization for high- and low-risk HPV. Eight cases (100%) of low-to-intermediate-grade adenoid cystic carcinoma were focally positive for p16, all of which were negative for HPV. In all, 14 of 16 cases (88%) of high-grade adenoid cystic carcinoma and three cases (100%) of dedifferentiated adenoid cystic carcinoma were positive for p16; strong and diffuse staining was noted in three cases (3 of 19, 16%). Two cases (11%) of high-grade adenoid cystic carcinoma, which were also diffusely positive for p16, showed the presence of high-risk HPV. These findings suggest that the presence of HPV infection in high-grade adenoid cystic carcinoma is infrequent, even in the presence of p16 immunostaining. Nevertheless, HPV positivity should not be used to exclude the possibility of high-grade adenoid cystic carcinoma when the differential diagnosis includes squamous cell carcinoma. Moreover, although p16 overexpression is often used as a surrogate marker for HPV in squamous cell carcinoma, it cannot be used in this manner in high-grade adenoid cystic carcinoma.

Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of Relevant Literature on Korean Women

Primary endometrial squamous cell carcinoma (PESCC) is an extremely rare tumor with unclear pathogenesis. A 54-year-old postmenopausal woman presented with a 6-month history of vaginal bleeding. The patient was provisionally diagnosed with uterine submucosal leiomyoma. This was followed by total hysterectomy with a bilateral salpingo-oophorectomy under the laparoscopic guidance. Histopathologically, the tumor was PESCC which was accompanied by a lack of the tumor in the uterine cervix. The tumor showed positive immunoreactivity for p16INK4a. But there was no evidence of human papillomavirus (HPV) on in situ hybridization and HPV DNA chip analysis. We also present a review of the relevant literature on Korean women.

No Evidence for Human Papillomavirus in the Etiology of Colorectal Polyps

While some studies have reported detection of oncogenic human papillomavirus (HPV) in colorectal tumors, others have not. We examined the association between oncogenic HPV infection and colorectal polyps in a case-control study of individuals with colorectal adenomas (n = 167), hyperplastic polyps (n = 87), and polyp-free controls (n = 250). We carried out real-time PCR for HPV-16 and -18 DNA, and SPF PCR covering 43 HPV types, on lesional and normal colorectal tissue samples. Plasma antibodies for oncogenic HPV types were assessed via a bead-based multiplex Luminex assay. HPV DNA was not found in any of the 609 successfully assayed colorectal tissue samples from adenomas, hyperplastic polyps, normal biopsies adjacent to polyps, or normal biopsies of the rectum of disease-free controls. Also, there was no association between HPV seropositivity for all oncogenic HPV types combined, for either polyp type, and for men or women. When analyses were restricted to participants without a history of polyps, among men [adenomas (n = 31), hyperplastic polyps (n = 28), and controls (n = 68)], there was an association between seropositivity and hyperplastic polyps when all oncogenic HPV types were combined (OR = 3.0; 95% CI: 1.1-7.9). Overall, our findings do not support an etiologic relationship between HPV and colorectal adenomas or hyperplastic polyps; however, our finding suggesting an association between HPV seropositivity and hyperplastic polyps in men may warrant further investigations. After stringent controls for contamination and three methods to assess HPV infection, we report no evidence for HPV in the etiology of colorectal neoplasia for either men or women.

Erratum: Limited evidence of human papillomavirus on breast tissue using molecular in situ methods

Erratum: Limited evidence of human papillomavirus on breast tissue using molecular in situ methods

Role of human papillomavirus infection in carcinogenesis of oral squamous cell carcinoma with evidences of prognostic association

Betel nut chewing, cigarette smoking and alcohol drinking are thought to be major environmental risk factors responsible for the development of oral squamous cell carcinomas. Oncogenic human papillomavirus infections have a well-established association with uterine cervical carcinoma. However, little is known about the exact role of human papillomavirus infections in oral squamous cell carcinomas. This study is designed to elucidate the role of human papillomavirus infections in cancer development and prognosis of oral squamous cell carcinomas. Molecular techniques including in situ hybridization and immunohistochemistry of p16(INK4A) and p53 for evidences of human papillomavirus in tissue micro-arrays were investigated. Twenty-four of 65 cases of oral squamous cell carcinomas were found positive for in situ hybridization and 14 were found positive for p16(INK4A). The majority of cases without the evidence of human papillomavirus were related to p53 over-expression. There were statistically significant correlations between the results of human papillomavirus test and size or extent of the tumor (P = 0.003) or the stage of oral squamous cell carcinomas (P = 0.015). Kaplan-Meier plot analysis demonstrated a tendency of longer survival in cases of oral squamous cell carcinomas with the evidence of human papillomavirus or positive p16 (INK4A). Human papillomavirus infections may play a unique role in oral carcinogenesis. Our data strongly suggest that human papillomavirus-positive oral squamous cell carcinomas comprise a distinct clinical and pathological disease entity that appears related to a better outcome with longer survival and bears a causally associated relationship different from other carcinogenic mechanisms.

Anal Cancer In Pregnancy

According to Cancer Research UK, anal cancer is a rare cancer; around 930 people are diagnosed in the United Kingdom each year. It is slightly more common in women than men, with rates increasing in women over the past 10 years. Around 8 out of 10 (80%) people diagnosed with anal cancer have evidence of Human Papillomavirus (HPV) infection in the anal area. Of the different types of HPV, type 16 is the most common in anal cancer. Invasive anal cancer is thought to develop from the growth of abnormal cells (squamous intraepithelial lesions) caused by HPV infection (1). Eighty-five percent of the anal cancers occur in the anal canal and 15% in the anal margin. There have been reported increased incidences of infection with HPV associated with female gender, with identified risk factors such as lifetime number of sexual partners, genital warts, receptive anal intercourse, and infection with human immunodeficiency virus (HIV) (2).

Evidence of Human Papillomavirus in the Placenta

Human papillomavirus (HPV) is an epitheliotropic virus typically infecting keratinocytes but also possibly epithelial trophoblastic placental cells. In the present study, we set out to investigate whether HPV can be recovered from transabdominally obtained placental cells to avoid any confounding contamination by HPV-infected cervical cells. Thirty-five placental samples from women undergoing transabdominal chorionic villous sampling were analyzed, and we detected HPV-16 and HPV-62 in 2 placentas. This study suggests that HPV infection of the placenta can occur early in pregnancy. The overall clinical implication of these results remains to be elucidated.

ACR Appropriateness Criteria ®: Local–Regional Therapy for Resectable Oropharyngeal Squamous Cell Carcinomas

The optimal management of resectable oropharyngeal squamous cell carcinomas is controversial with many treatment options, both surgical and nonsurgical approaches, supported by published experiences with no randomized trials comparing commonly accepted treatments. The treatment decisions are further complicated by the need for local-regional disease control and competing goals to preserve salivary and swallow function. Treatment decisions may also be affected by tumor and patient related factors and a history of environmental exposure to tobacco and evidence of human papilloma virus. We summarize the published literature and provide treatment consensus derived from the modified Delphi methodology.