Genetic diversity in L1 ORF of human papillomavirus in women with cervical cancer with and without human immunodeficiency virus in Botswana and Kenya.

BACKGROUND: The variation of human papillomavirus (HPV) genotypes shapes the risks of cervical cancer and these variations are not well defined in Africa. Nucleotide changes within the L1 gene, nucleotide variability, and phylogeny were explored in relation to HIV in samples from Botswana and Kenya. METHODS: A total of 98 HPV-positive cervical samples were sequenced to identify different HPV variants. Phylogenetic inferences were used to determine HPV genotypes and investigate the clustering of sequences between women living with HIV (WLWHIV) and -women not living with HIV (WNLWHIV). RESULTS: Out of 98 generated sequences, 83.7% (82/98) participants had high-risk (HR) HPV genotypes while 16.3% (16/98) had low-risk (LR) HPV genotypes. Among participants with HR-HPV genotypes, 47.6% (39/82) were coinfected with HIV. The prevalence of HR-HPV genotypes was statistically higher in the Botswana population compared to Kenya (p-value < 0.001). Multiple amino acid mutations were identified in both countries. Genetic diversity differed considerably among WLWHIV and WNLWHIV. The mean pairwise distances between HPV-16 between HIV and HIV/HPV as well as for HPV-18 were statistically significant. Six (6) new deleterious mutations were identified in the HPV genotypes based on the sequencing of the L1 region, HPV-16 (L441P, S343P), HPV-18 (S424P), HPV-45 (Q366H, Y365F), and HPV-84 (F458L). The majority of the patients with these mutations were co-infected with HIV. CONCLUSIONS: Genomic diversity and different genomic variants of HPV sequences were demonstrated. Candidate novel mutations within the L1 gene were identified in both countries which can be further investigated using functional assays.

Human papillomavirus-related cancer risk for solid organ transplant recipients during adult life and early prevention strategies during childhood and adolescence.

Malignancies are among the top three causes of patient death in pediatric and adult kidney transplant (KT) recipients. Solid organ transplant (SOT) recipients, including KT individuals, experience more cancer compared with the general population, including human papillomavirus (HPV)-related anogenital and oropharyngeal cancers. This article describes the epidemiology, pathophysiology and natural history of the HPV infection in both the general population and in SOT recipients, as well as its role in the development of HPV-related pre-cancerous lesions and cancers. Emphasis is given to the primary prevention strategy, HPV vaccination in SOT recipients, and its particularities compared with the general population. Secondary prevention strategies in SOT recipients are discussed and compared with the general population, highlighting cervical cancer screening needs within SOT populations. The article emphasizes how these primary and secondary HPV prevention strategies applied during childhood and adolescence by the pediatric transplant professionals, can lower the burden of HPV-related cancers for SOT recipients in subsequent years, during their adult life.

Episodic detection of human papillomavirus within a longitudinal cohort of young women.

Redetection of a type-specific human papillomavirus (HPV) infection may represent reinfection. However, a growing body of literature suggests that reactivation of HPV is common and that episodic detection of a HPV infection may represent reactivation of a persistent virus. A cohort of prospectively followed adolescent women (N = 150), ages 14-17, was observed on average 6.4 years. The authors describe the redetection of 37 HPV types and associated factors of redetection of high-risk (HR) and low-risk (LR) types using Cox proportional hazard models. Of 1,248 HPV type-specific infections, 286 (22.9%) were associated with redetection after apparent clearance. Chlamydia infections (HR = 1.99 [95%CI, 1.15-3.49]) and non-condom use (HR = 1.1 [95%CI, 1.04-1.99]) were associated with increased redetection of HR-HPV infections. Oral contraceptive pills (HR = 2.73 [95%CI, 1.52-4.90]) and number of sexual partners (HR = 1.44 [95%CI, 1.04-1.99]) were associated with increased redetection of LR-HPV infections. Episodic detection of HPV is common for HR- and LR-HPV types. This finding and identified factors or redetection have clinical implications and enhances the understanding of HPV natural history.

DNA detection and seroprevalence of human papillomavirus in a cohort of adolescent women.

OBJECTIVES: Human papillomavirus (HPV) infections are common in adolescent women, while the rare cancerous sequelae of HPV infections do not generally occur until the 4th or 5th decades of life. This prospective study of a cohort of adolescent women was performed to further our knowledge of the natural history of incident and prevalent HPV infections. METHODS: Self-vaginal swabs collected from high-risk, unvaccinated adolescent women in a longitudinal study were analysed for HPV DNA. Sera were collected at enrolment and later tested for HPV antibodies. Statistical analysis was performed to determine the HPV genotype distribution and duration of detection, and to determine rates of seropositivity and seroconversion for HPV types represented in the assays. RESULTS: 146 subjects (mean enrolment age=15.4 years; mean duration of follow-up=5.8 years) had samples adequate for analysis of HPV detection, and 95 of these subjects had paired sera available. The cumulative prevalence for high-risk and low-risk HPV types was 95.9% and 91.1%, respectively. HPV types 6, 11, 16 and 18 (HPV types represented in the quadrivalent vaccine) were found at some point in 40.4%, 6.2%, 48% and 24% of participants, respectively. Serological data confirmed exposure to these vaccine-covered types, as well as to other high-risk HPV types. CONCLUSIONS: In this cohort of adolescent women, high- and low-risk HPV types were frequently detected, and serological data confirmed exposure in most subjects. The high-prevalence HPV types represented in the quadrivalent HPV vaccine further support vaccination of women at an age well before sexual debut.

Association of Chlamydia trachomatis infection with redetection of human papillomavirus after apparent clearance.

BACKGROUND: Persistent infection with oncogenic human papillomavirus (HPV) is associated with an increased risk of cervical malignancy. Redetection of type-specific HPV after a period of nondetection may be caused by reactivation of a low-level persistent infection. Little is known about factors associated with type-specific HPV redetection. METHODS: For a longitudinal cohort of adolescent women with frequent behavioral and sexually transmitted infection (STI) information (every 3 months), Cox proportional hazard models were used to assess the influence of sexual behaviors and STIs on the redetection of oncogenic or high-risk HPV infections. RESULTS: A total of 210 type-specific high-risk HPV detection episode periods were identified in this longitudinal cohort; 71 (33.8%) were characterized by a period of nondetection followed by redetection. Chlamydia trachomatis (hazard ratio [HR], 3.14; 95% confidence interval [CI], 1.44-6.86) was associated with redetection; redetection was >2 times more likely with each additional self-reported sex partner in the past 3 months (HR, 2.26; 95% CI, 1.35-3.78). CONCLUSIONS: This study demonstrates the role of C. trachomatis and number of recent sexual partners in type-specific HPV redetection. Given that persistent oncogenic HPV infections are associated with cancer-related outcomes, understanding the potential role of such factors in the pathogenesis of HPV-related outcomes is important.

EBV-Gastritis Preceded the Development of Nasopharyngeal EBV (+) Diffuse Large B Cell Lymphoma in a Patient With Ruxolitinib-Induced Immunosuppression.

Epstein-Barr virus (EBV) is acquired early in life as asymptomatic or symptomatic infectious mononucleosis (IM) and remains latent in a few B cells in most individuals. Pathologic EBV-reactivation affects immunosuppressed individuals and manifests as IM-like syndromes, polyclonal lymphoproliferative disorders, EBV-related lymphomas, and carcinomas. EBV-associated gastritis is an underrecognized and very rarely reported entity. We report a case of a 65-year-old woman with ruxolitinib-treated polycythemia vera, who developed EBV viremia and EBV gastritis. The patient improved after the ruxolitinib dose reduction and administration of antiviral therapy. A few months after discontinuation of the antiviral therapy the gastric symptoms recurred, numerous gastric ulcers were identified, and a nasopharyngeal mass was detected. A biopsy of the nasopharynx showed an EBV (+) diffuse large B cell lymphoma. Ruxolitinib was discontinued and the patient was started on rituximab monotherapy with a resolution of symptoms and pathologic improvement. Our case supports earlier reports of an association of ruxolitinib therapy with EBV complications. An early diagnosis of EBV gastritis in immunocompromised patients is important since the gastric infection may precede or co-exist with a developing EBV-associated malignancy. Our case and existing literature suggest that EBV gastritis in symptomatic patients with iatrogenic immunosuppression requires discontinuation of immunosuppressive therapy if feasible, treatment with antivirals, and close surveillance for possible evolving/concurrent EBV (+) malignancy.

Sexual Network Patterns and Their Association With Genital and Anal Human Papillomavirus Infection in Adolescent and Young Men.

PURPOSE: This study aimed to determine individual- and partner-level factors associated with human papillomavirus (HPV) infection in vaccinated and unvaccinated men. METHODS: A total of 747 men, aged 13-26 years, completed a survey of sexual behaviors and were tested for genital and perianal/anal HPV (36 types). Sexual network variables included recent and lifetime concurrency (being in more than one sexual relationship at the same time) and recent sex partner discordance (by race, ethnicity, age, and number of sexual partners). We determined individual-level and sexual network variables associated with ≥1 HPV type and HPV16/18, stratified by vaccination status, using separate multivariable logistic regression models. RESULTS: Participants' mean age was 21.2 years; 64% were positive for ≥1 HPV type and 21% for HPV16/18. Factors associated with ≥1 HPV type in unvaccinated men included recruitment site and lifetime concurrency. Factors associated with ≥1 HPV type among vaccinated men included recruitment site, Chlamydia history, main male partner, number of lifetime female partners, and no condom use with female partner. Factors associated with HPV16/18 in unvaccinated men included race and partner concurrency. Factors associated with HPV16/18 in vaccinated men included ethnicity, main male partner, and recent concurrency. CONCLUSIONS: Sexual network variables associated with HPV infection were different based on vaccination status and HPV type, suggesting risk factors for HPV infection may change as the proportion of vaccinated men increases. In addition, participant report of concurrency and not knowing whether one had practiced concurrency were consistent risk factors; clinicians should consider including concurrency in the sexual history to determine the risk of HPV.

Detection of types of HPV among HIV-infected and HIV-uninfected Kenyan women undergoing cryotherapy or loop electrosurgical excision procedure.

OBJECTIVE: To assess the baseline types of HPV infection among HIV-positive and HIV-negative women in western Kenya undergoing cryotherapy or loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia. METHODS: A prospective observational study was conducted of baseline HPV characteristics of women undergoing visual inspection with acetic acid (VIA) and cryotherapy or LEEP. After a positive VIA in HIV-positive and HIV-negative women, data on demographics, CD4 count, and use of antiretroviral therapy and a cervical swab were collected. HPV typing was performed using the Roche Linear Array. RESULTS: Of 175 participants, 86 (49.1%) were HIV-positive and had a higher prevalence of low-risk HPV types (odds ratio [OR] 5.28, P=0.005) compared with HIV-negative women. The most common high-risk (HR)-HPV types in HIV-positive women were HPV 16 (13.9%) and HPV 18 (11.1%). HIV-positive women requiring LEEP were more likely to have HR-HPV types (OR 6.67, P=0.012) and to be infected with multiple HR-HPV types (OR 7.79, P=0.024) compared to those undergoing cryotherapy. CONCLUSION: HIV-positive women requiring LEEP versus cryotherapy had a higher prevalence of any HR-HPV type and multiple HR-HPV types. There were no such differences in HPV types identified among HIV-negative women.

Decline in vaccine-type human papillomavirus prevalence in young men from a Midwest metropolitan area of the United States over the six years after vaccine introduction.

PURPOSE: The aim of this study was to determine changes in human papillomavirus (HPV) prevalence among young men from a Midwest metropolitan area over the six years after vaccine introduction, including HPV prevalence in men overall, in vaccinated men to examine vaccine impact and in unvaccinated men to examine herd protection. An exploratory aim was to examine associations between number of vaccine doses and HPV prevalence. METHODS: Men aged 14-26 years reporting male-female and/or male-male sexual contact were recruited from a primary care clinic, sexually transmitted disease clinic, and community setting during two waves of data collection: 2013-2014 (N = 400) and 2016-2017 (N = 347). Participants completed a questionnaire and were tested for penile, scrotal and anal HPV. Changes in prevalence of any (≥1 type) and vaccine-type HPV (HPV6, 11, 16, and/or 18) were examined using propensity score weighted logistic regression. Associations between number of doses and HPV infection were determined using chi-square tests and logistic regression. RESULTS: The proportion of men with a history of ≥1 HPV vaccine doses increased from 23% to 44% (p < 0.001) from waves 1 to 2. After propensity score weighting, infection with ≥1 vaccine-type HPV significantly decreased among all men (29% to 20%; 31% decrease; odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.44-0.88) and unvaccinated men (32% to 21%; 36% decrease; OR = 0.56, 95%CI = 0.34-0.86); there was a non-significant decrease (21%) among vaccinated men. Associations between number of doses and HPV prevalence were not statistically significant. CONCLUSIONS: Prevalence of vaccine-type HPV decreased among all, vaccinated, and unvaccinated men six years after HPV vaccine recommendation, supporting vaccine impact and herd protection. Decreases in vaccine-type HPV in all men appear to be due to decreases in unvaccinated men, suggesting that the full impact of vaccination has yet to be realized. Continued monitoring and efforts to vaccinate men prior to sexual initiation are warranted.