APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma.

APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC-induced mutations observed in both human cancers and HPV genomes are directly linked. We performed sequencing of host somatic exomes, transcriptomes, and HPV16 genomes from 79 HPV + OPSCC samples, quantifying APOBEC mutational burden and activity in both host and virus. APOBEC was the dominant mutational signature in somatic exomes. In viral genomes, there was a mean of five (range 0-29) mutations per genome. The mean of APOBEC mutations in viral genomes was one (range 0-5). Viral APOBEC mutations, compared to non-APOBEC mutations, were more likely to be low-variant allele fraction mutations, suggesting that APOBEC mutagenesis actively occurrs in viral genomes during infection. HPV16 APOBEC-induced mutation patterns in OPSCC were similar to those previously observed in cervical samples. Paired host and viral analyses revealed that APOBEC-enriched tumor samples had higher viral APOBEC mutation rates (p = 0.028), and APOBEC-associated RNA editing (p = 0.008), supporting the concept that APOBEC mutagenesis in host and viral genomes is directly linked and occurrs during infection. Using paired sequencing of host somatic exomes, transcriptomes, and viral genomes, we demonstrated for the first-time definitive evidence of concordance between tumor and viral APOBEC mutagenesis. This finding provides a missing link connecting APOBEC mutagenesis in host and virus and supports a common mechanism driving APOBEC dysregulation.

Development of a ß-HPV vaccine: Updates on an emerging frontier of skin cancer prevention.

Human papillomaviruses (HPVs) are small, non-enveloped, doublestranded DNA viruses. Over 200 subtypes of HPV have been identified, organized into five major genera. ß-HPVs are a group of approximately 50 HPV subtypes that preferentially infect cutaneous sites. While α-HPVs are primarily responsible for genital lesions and mucosal cancers, growing evidence has established an association between ß-HPVs and the development of cutaneous squamous cell carcinomas. Given this association, the development of a vaccine against ß-HPVs has become an important topic of research; however, currently licensed vaccines only provide coverage for genital HPVs, leaving ß-HPV infections and their associated skin cancers unaddressed. In this review, we summarize the current advances in ß-HPV vaccine development, including progress made in preclinical testing and limited clinical data. We also discuss novel findings in the viral pathomechanisms involved in ß-HPV cutaneous tumorigenesis that may play a large role in future vaccine development. We hope that synthesizing the available data and advances surrounding ß- HPV vaccine development will not only lead to increased dedication to vaccine development, but also heightened awareness of a future vaccine among clinicians and the public.

Oral HPV prevalence and HPV vaccination among special needs population in the US.

INTRODUCTION: Special needs population have barriers accessing healthcare, higher incidence of sexual assaults and lower sexual education. Due to the above this study was conducted- 1) To assess the current prevalence of oral HPV infection among individuals with SHCN (special health care needs) as compared to the general population and 2) To compare the prevalence of HPV vaccination in SHCN individuals (within the recommended age groups) to general population. METHODS: This data was obtained from NHANES 2013-14 and included 665 individuals with special needs. Weighted prevalence estimates and prevalence ratios (PR) were calculated for oral HPV infection by gender, age (18-59 years), race, smoking history, economic status, and sexual behavior. Prevalence rates were calculated for HPV vaccination. RESULTS: Oral HPV was detected in 9% (7.1-11.5; p = 0.05) of special needs adults. High-risk HPV genotypes prevalence was also higher among adults with special needs [5.56% (3.9-7.9) vs 3.87% (2.7-5.4)]. The HPV vaccination rates among 9-26 years special needs females (33.5% vs 37%) and males aged 9-21 years (16.7% vs 21.2%) with special needs was lower than non-special needs individuals. CONCLUSION: There is higher burden of oral HPV infection among adults with special needs compared to general population. Contrastingly, lower vaccination rates were observed among them within the recommended age groups. Further studies are required to determine the barriers to HPV vaccination among individuals with special needs.

Human papillomavirus infection among women attending family planning clinic in Nigeria: prevalence, correlates, and co-infection with Chlamydia trachomatis.

Infection with high-risk genotypes of human papillomavirus (HPV) is considered the main cause of invasive cervical. A number of epidemiologic studies have suggested that HPV and Chlamydia trachomatis (CT) play a synergistic role in the etiology of cervical intraepithelial neoplasia and subsequent cervical cancer. The current study aimed to evaluate the HPV prevalence and the risk factors for co-infection with CT among women attending family planning clinic in Nigeria. Following enrolment, 90 patients were screened for IgG antibodies to virus-like proteins of HPV types 6, 8, 16, and 18. CT seropositivity was tested by enzyme-linked immunosorbent assay for the detection of IgG and IgM antibodies. The prevalence of HPV IgG was 20%. Seropositivity for CT IgM was 77.8% while the IgG was 0%. A total of 10 women (11.1%) were seropositive for both CT IgM and HPV IgG antibodies. Seropositivity for HPV IgG was significantly associated with age at marriage (P < 0.001), current Chlamydia infection (P < 0.011), and number of children (P < 0.025), while seropositivty for HPV IgG and Chlamydia trahomatis IgM was significantly associated with age at coitarche (P < 0.028), number of life sex partners (P < 0.033), and history of multiple sexual partners (P < 0.002).

The Study of Low-risk and High-risk Human Papillomaviruses Infection in cervical Carcinomas and Cervical Instaepithelial Lesions with Hybrid Capture system / 대한산부인과학회잡지

The assocication between human papillomavirus infection (HPV) and cervical lesionhas been well established. for detection and typing human papilloma virus deoxyribonucleic acid in cervical tissues, Southern blot hybridzation and polymerase chain reaction are commonly regarded as reference standard methods. However it has the limitation includeing technical difficulty, safety, subjectivey in result interpretation. Recently the chemilnuminescent molecular hybridization assay method has been windely used and it has been known that it can detect less hybridization assay method has been windely used and it has been known that it can detect less then 1 pg of DNA in a 100n1 aliquot of a crude specimen. This study was perfomed to determine the usefulness of hybrid capture HPV DNA assay for detecting low-risk and high-risk human papillomaviruses in histologically confirmed normal, cervical intraepithelial lesion(CIN) and invasive squamous cell carcinoma of the cervix, and to compare the correlation among cervical cytology, hiopsy finding and HPVs infelction ,and to detirmine whether the additon of the hybrid capture test to cytologic studies would improve the ability to identify signifcant lesions. Cervical cytologic smears, hybrid capture HPVs DNA assay, and pucnh bhiopsies were performed on 78 women who have normal cervix(28cases),cervical intraepithelila lesion (24cases), and invasive squamous cell carcinoma(26cases). At first the probes for low-risk HPV(6,11,42,43,44) and the proves for high-risk HPV(16,18,31,33,35,45,51,52,56)were used and secondly retyping was done for HPV 16 abd 18 in high-risk HPV positive cases.the results obtained were as follows; 1. Low-risk HPVs infections were 14.3% and 8.3% in normal cervix and cervical intraepithelial lesion respectively. High-risk HPVs infection were 7.1%, 70.8% and 73.1% in normal cervix, cervical intraeithelial lesion and squamous cell carcinoma respecitively. These was highly significant corelation between positive high-risk HPVs test, cervical intraepithelial lesion and squamous cell carcinoma. 2. Positivities of low and high-risk human papillomaviruses in patients with negative cytologic result were 9.1% and 15.1% respectinvely. 3. In patients with high-risk human papillomaviruses infection, human papilloma viurs 16 and 18 types were detected in 47.4% and 13.2%, respectinvely, and both HPV 16 and 18 positive and negative detention were 15.7% 23.7% respectinvely. Among 12patinent of cervical intraepithelial neoplasia with high risk HPVs infection, HPV 16 was detected in 66.6% and HPV 18 in 16.7% Among 24 squamous cell carcinomas with high risk HPVs infection, HPV 16was detected in 41.7% and HPV 16 in 12.5% and both HPV and 18 in 25% 4. In patients without koilocytosis by cervical tytology, low and high-risk human papillomaviruses or both were positive in 30.7% 5. In patients with positive high-risk HPVs, sensitivitives of koilocytosis were 64% and 69% in histologic and cytologc diagnosis, and specificities and specifictites were 58.5% and 62% respectively. Above result suggest that detection for high-risk human papilloma viruses type by hybrid capture assay improves the management of cervical intraepithelial neoplasia and is more useful method over cervical cytology only.

The Study of Low-risk and High-risk Human Papillomaviruses Infection in cervical Carcinomas and Cervical Instaepithelial Lesions with Hybrid Capture system / 대한산부인과학회잡지

The assocication between human papillomavirus infection (HPV) and cervical lesionhas been well established. for detection and typing human papilloma virus deoxyribonucleic acid in cervical tissues, Southern blot hybridzation and polymerase chain reaction are commonly regarded as reference standard methods. However it has the limitation includeing technical difficulty, safety, subjectivey in result interpretation. Recently the chemilnuminescent molecular hybridization assay method has been windely used and it has been known that it can detect less hybridization assay method has been windely used and it has been known that it can detect less then 1 pg of DNA in a 100n1 aliquot of a crude specimen. This study was perfomed to determine the usefulness of hybrid capture HPV DNA assay for detecting low-risk and high-risk human papillomaviruses in histologically confirmed normal, cervical intraepithelial lesion(CIN) and invasive squamous cell carcinoma of the cervix, and to compare the correlation among cervical cytology, hiopsy finding and HPVs infelction ,and to detirmine whether the additon of the hybrid capture test to cytologic studies would improve the ability to identify signifcant lesions. Cervical cytologic smears, hybrid capture HPVs DNA assay, and pucnh bhiopsies were performed on 78 women who have normal cervix(28cases),cervical intraepithelila lesion (24cases), and invasive squamous cell carcinoma(26cases). At first the probes for low-risk HPV(6,11,42,43,44) and the proves for high-risk HPV(16,18,31,33,35,45,51,52,56)were used and secondly retyping was done for HPV 16 abd 18 in high-risk HPV positive cases.the results obtained were as follows; 1. Low-risk HPVs infections were 14.3% and 8.3% in normal cervix and cervical intraepithelial lesion respectively. High-risk HPVs infection were 7.1%, 70.8% and 73.1% in normal cervix, cervical intraeithelial lesion and squamous cell carcinoma respecitively. These was highly significant corelation between positive high-risk HPVs test, cervical intraepithelial lesion and squamous cell carcinoma. 2. Positivities of low and high-risk human papillomaviruses in patients with negative cytologic result were 9.1% and 15.1% respectinvely. 3. In patients with high-risk human papillomaviruses infection, human papilloma viurs 16 and 18 types were detected in 47.4% and 13.2%, respectinvely, and both HPV 16 and 18 positive and negative detention were 15.7% 23.7% respectinvely. Among 12patinent of cervical intraepithelial neoplasia with high risk HPVs infection, HPV 16 was detected in 66.6% and HPV 18 in 16.7% Among 24 squamous cell carcinomas with high risk HPVs infection, HPV 16was detected in 41.7% and HPV 16 in 12.5% and both HPV and 18 in 25% 4. In patients without koilocytosis by cervical tytology, low and high-risk human papillomaviruses or both were positive in 30.7% 5. In patients with positive high-risk HPVs, sensitivitives of koilocytosis were 64% and 69% in histologic and cytologc diagnosis, and specificities and specifictites were 58.5% and 62% respectively. Above result suggest that detection for high-risk human papilloma viruses type by hybrid capture assay improves the management of cervical intraepithelial neoplasia and is more useful method over cervical cytology only.