Latent Human Papillomavirus Infection Research Articles

Latent Human Papillomavirus (HPV) Infection: Does HPV Last Forever in Some Women?

Journal of Women's HealthAhead of Print Latent HPV Infection: Does HPV Last Forever in Some Women?Patress Persons, Margaret Long, and Suneela VeguntaPatress PersonsDivision of Community Internal Medicine, Mayo Clinic, Scottsdale, Arizona, USA.Search for more papers by this author, Margaret LongDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA.Search for more papers by this author, and Suneela VeguntaAddress correspondence to: Suneela Vegunta, MD, FACP, NCMP, Division of Women's Health—Internal Medicine, Mayo Clinic, Scottsdale, AZ 85260, USA E-mail Address: vegunta.suneela@mayo.eduDivision of Women's Health—Internal Medicine, Mayo Clinic, Scottsdale, Arizona, USA.Search for more papers by this authorPublished Online:13 Mar 2023https://doi.org/10.1089/jwh.2022.0436AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Latent HPV Infection: Does HPV Last Forever in Some Women?." Journal of Women's Health, , pp. –FiguresReferencesRelatedDetails Volume 0Issue 0 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Patress Persons, Margaret Long, and Suneela Vegunta.Latent HPV Infection: Does HPV Last Forever in Some Women?.Journal of Women's Health.ahead of printhttp://doi.org/10.1089/jwh.2022.0436Online Ahead of Print:March 13, 2023PDF download

Evidence of latent HPV infection in older Danish women with a previous history of cervical dysplasia.

Understanding whether human papillomavirus (HPV) may establish latency in the uterine cervix is important. A better understanding of HPV natural history is useful for clinical counseling of women attending screening and to accurately inform health prevention strategies such as screening and HPV vaccination. We evaluated the extent of latent HPV infections in older women with a history of abnormal cytology. We conducted a cross-sectional study in Aarhus, Denmark, from March 2013 through April 2015. Women were enrolled if they underwent cervical amputation or total hysterectomy because of benign disease. Prior to surgery, women completed a questionnaire and a cervical smear was collected for HPV testing and morphological assessment. For evaluation of latency (i.e., no evidence of active HPV infection, but HPV detected in the tissue), we selected women with a history of abnormal cervical cytology or histology, as these women were considered at increased risk of harboring a latent infection. Cervical tissue underwent extensive HPV testing using the SPF10-DEIA-LipA25 assay. Of 103 women enrolled, 26 were included in this analysis. Median age was 55 years (interquartile range [IQR] 52-65), and most women were postmenopausal and parous. The median number of sexual partners over the lifetime was six (IQR 3-10), and 85% reported no recent new sexual partner. Five women (19.2%) had evidence of active infection at the time of surgery, and 19 underwent latency evaluation. Of these, a latent infection was detected in 11 (57.9%), with HPV16 being the most prevalent type (50%). Nearly 80% (n = 14) of the 18 women with a history of previous low-grade or high-grade cytology with no treatment had an active or latent HPV infection, with latent infections predominating. HPV was detected in two of the six women with a history of high-grade cytology and subsequent excisional treatment, both as latent infections. HPV can be detected in cervical tissue specimens without any evidence of an active HPV infection, indicative of a latent, immunologically controlled infection. Modeling studies should consider including a latent state in their model when estimating the appropriate age to stop screening and when evaluating the impact of HPV vaccination.

Human Papillomavirus-Negative Cervical Cancer: A Comprehensive Review.

Human papillomavirus (HPV) has been the leading cause of cervical cancer for over 25 years. Approximately 5.5–11% of all cervical cancers are reported to be HPV-negative, which can be attributed to truly negative and false-negative results. The truly HPV-negative cervical cancers are almost all cervical adenocarcinomas with unclear etiology. False HPV negativity can arise from histological misclassification, latent HPV infection, disruption of the targeting fragment, non-high risk HPV infection, and HPV testing methods. HPV-negative cervical cancers are often diagnosed at an advanced FIGO stage and have a poor prognosis; thus, the management of these cases requires greater attention.

Surgical Treatment of Vulvar HSIL: Adjuvant HPV Vaccine Reduces Recurrent Disease

Data suggest that adjuvant human papillomavirus (HPV)-vaccination in women treated for cervical HPV diseases reduces recurrent disease. This study investigates adjuvant HPV-vaccination and the rate of recurrence in women undergoing surgery for vulvar high-grade squamous intraepithelial lesions (HSIL). From January 2013 to April 2020, we enrolled 149 women in a prospective case-control study. The control group (NV-group) was treated by standard surgery alone, while the study group received adjuvant vaccination soon after surgery (V-group). A follow-up was performed by vulvoscopy and HPV test. Statistical analysis was performed by Fisher’s exact test. HSIL recurrence was observed in 24/76 (32%) patients in NV-group and in 8/42 patients (19%) of the vaccinated group. By analysing the recurrence rate related to the incident and reactivated latent HPV infection, we found a significant difference between (17/76) 22.3% in NV-group and (2/42) 4.8% in V-group (p = 0.01). A reduction of 78.5% in incident/reactivated HPV infections was demonstrated. Data results add to the current knowledge about the mechanism of post-surgical adjuvant HPV vaccination. Our prospective study is the first to document the vaccine clinical effectiveness in preventing “reactivation” of latent HPV infections. Quadrivalent HPV vaccine administered after the surgical treatment for vulvar HSIL appears to be useful in preventing recurrent disease.

Estimated impact of human papillomavirus vaccines on infection burden: The effect of structural assumptions

Mathematical models have been used to estimate the impact of human papillomavirus (HPV) vaccines on infection burden and cervical cancer. Models assume different mechanisms of naturally acquired immunity against re-infection, but processes of latency and reactivation of latent infection have not been explored. This study uses an individual-based dynamic model to simulate randomised controlled trials (RCTs) for vaccine efficacy, using different assumptions about naturally acquired immunity and viral latency after clearance of HPV infection. Model estimates of vaccine effectiveness are compared to those from published RCTs. We then estimate the impact of the bivalent vaccine on HPV-16 and -18 infection burden in South Africa under these different assumptions. When assuming no latency, simulated vaccine effectiveness overestimates results from RCTs and the model cannot match the observed difference in vaccine effectiveness between total vaccinated cohorts and more HPV-naïve cohorts. The reduction in HPV-16 and -18 burden by 2045, following roll-out of vaccination in 2014, does not depend on assumptions about natural immunity, but models that assume no latency predict ∼25% greater reduction in HPV-16 and -18 burden than models that include reactivation of latent infection for all men and women. Mathematical models that do not allow for reactivation of latent HPV infections may therefore overestimate the long-term impact of HPV vaccines.

Laryngopharyngeal Reflux Is a Potential Risk Factor for Juvenile-Onset Recurrent Respiratory Papillomatosis.

Introduction Human papillomavirus (HPV) causes juvenile-onset recurrent respiratory papillomatosis (JORRP). Although HPV is common in children, the prevalence of JORRP is low. It is likely that other factors contribute to the pathogenesis of JORRP, during either activation or reactivation of a latent HPV infection. There is evidence that laryngopharyngeal reflux (LPR) might be such a risk factor for adult-onset recurrent respiratory papillomatosis. This study investigated if LPR might also be a risk factor for JORRP. Materials and Methods Children with JORRP of the larynx that required microlaryngoscopy at a tertiary referral hospital were included in this prospective case-series study from November 2015 to November 2017. Using immunohistochemistry, HPV infection and pepsin associated with LPR were diagnosed from laryngeal biopsies. Results Eleven children (aged 4-14 years) were analyzed. No patient had a history of immunodeficiency or tobacco smoke exposure. All patients underwent at least three previous surgeries due to JORRP and had been vaccinated against HPV in the past. Five children were treated using antivirotics and immunomodulators. The only known maternal risk factor was that three mothers were primiparous. All 11 samples were infected with HPV (type 6 or 11). Pathologic LPR was diagnosed in 5/11 children (45.5%). Conclusion LPR may be a risk factor for JORRP, contributing to its development by activating or reactivating a latent HPV infection. Results are in accordance with those from our previous study in adults.

Pathological mechanisms of laryngeal papillomatosis based on laryngeal epithelial characteristics.

ObjectivesHuman papillomavirus (HPV) infects basal cells of the stratified squamous epithelium through micro epithelial trauma. However, laryngeal papillomatosis commonly appears in any site on the laryngeal mucosa not covered by stratified squamous epithelium. The purpose of this study is to clarify pathological mechanisms of laryngeal papillomatosis based on the characteristics of the laryngeal epithelium.Study DesignMorphological and immunohistochemical study.MethodsLarynges from one newborn and two adults were used. Morphological differences in the laryngeal squamo‐ciliary junction (lSCJ) were compared to those in the cervical squamo‐columnar junction (cSCJ) in a resected cervix uterus. Morphological characteristics of laryngeal epithelial distribution were also compared between the newborn and adult larynges. Immunohistochemical evaluations were performed using p63 (an epithelial stem‐cell marker) and integrin‐α6 (a cellular HPV receptor).ResultsMorphological differences were noted between the lSCJ and the cSCJ. The lSCJ was present in the adult, but not the newborn supraglottis. Goblet cells in the pseudostratified ciliated columnar epithelium were also found in the adult but not the newborn larynx. In addition, basal cells of the stratified squamous epithelium as well as the pseudostratified ciliated columnar epithelium expressed p63 and integrin‐α6 in both newborn and adult larynges.ConclusionsHPV can infect any immature laryngeal epithelium with or without the lSCJ. Squamous metaplasia of pseudostratified ciliated columnar epithelium with a latent HPV infection can also cause tumorigenesis.Level of EvidenceN/A

Efficacy and safety of combined high-dose interferon and red light therapy for the treatment of human papillomavirus and associated vaginitis and cervicitis: A prospective and randomized clinical study.

Background:We evaluated the efficacy and safety of combined high-dose interferon (IFN) and red light therapy for the treatment of subclinical and latent human papillomavirus (HPV) infections.Methods:Ninety women diagnosed with subclinical or latent HPV infection were randomized to receive topical application of low-dose recombinant IFNα-2b (1 million IU), high-dose IFNα-2b (9 million IU), or a combination of high-dose IFNα-2b and red light therapy on the cervix and vagina. All patients received treatment once daily for 4 weeks. HPV titer was measured immediately and 4, 8, and 12 weeks after treatment to determine the rates of viral clearance and infection cure. Treatment of HPV-associated vaginitis and cervicitis was also evaluated.Results:Results showed that immediately and 4, 8, and 12 weeks after treatment, the HPV clearance rates and infection cure rates were higher in the high-dose IFN and combination groups compared to the low-dose IFN group. High-dose IFN and combination therapies were significantly effective against both low-risk and high-risk HPV infections. Although the cure rates for vaginitis and cervicitis were significantly higher in the high- compared to the low-dose IFN group, rates were even higher in the combination group compared to the high-dose IFN group. Mild adverse effects were reported by a very small subset of patients (3/30) in the combination group.Conclusions:This study suggests that combination of high-dose IFN and red light therapy is safe and effective against subclinical and latent HPV infections.

Detection of Incident Anal High-Risk Human Papillomavirus DNA in Men Who Have Sex With Men: Incidence or Reactivation?

We aimed to assess whether sexual exposure may explain all incident anal human papillomavirus (HPV) detections among men who have sex with men (MSM). A longitudinal study among MSM was conducted between 2010 and 2013 with visits every 6 months and up to 24 months of follow-up. Risk-factor questionnaires, blood samples, and anal and penile self-swabs were collected at each visit. Self-swabs were used for detection and genotyping of HPV by the broad spectrum L1 based SPF10 PCR DNA/enzyme immunoassay LiPA25 system. Serum samples were tested for high-risk HPV (hrHPV) antibodies. Incident anal HPV detection rates among sexually non-, low, and highly exposed MSM were compared. Factors associated with incident anal hrHPV detection were assessed using multivariable Cox regression. Seven hundred fourteen men (median age, 40 years; 39% human immunodeficiency virus [HIV] infected) were included in the analysis. Incident anal detections of all hrHPV types were observed among both sexually nonexposed and exposed MSM. In multivariable analyses, being highly sexually exposed, being HIV infected, and having a penile HPV infection were positively associated with incident anal HPV detection; those reporting more sex partners had a nonsignificantly increased risk of HPV detection. Incident anal hrHPV detection is common among recently nonexposed MSM, suggesting that a reactivated latent HPV infection instead of an incident infection may underlie incident HPV detection.

Quality Improvement to Demonstrate the Lack of Reliability of the Human Papillomavirus mRNA Assay to Identify Women With Latent Human Papillomavirus Infections.

To assess the consistency between human papillomavirus (HPV) mRNA testing in women with a history of previous HPV infections diagnosed by HPV DNA assay and the potential effects on follow-up HPV screening. This was a quality improvement study that used data from a pathology laboratory software database reviewed from November 2014 to June 2016 to identify female patients aged 30 years or older with greater than one HPV-positive result, including one or more HPV mRNA assay results and one or more documented HPV DNA assay results for comparison. Previous correlative cytology and colposcopic histopathology were also documented. American College of Obstetricians and Gynecologists' cervical cancer screening guidelines were used to compare potential differences in follow-up recommendations. Four hundred twenty-five charts for female patients 30 years of age or older were identified with one or more prior high-risk HPV infections by DNA assay. There was a 69.3% difference in HPV mRNA results compared with previous HPV DNA-positive results. There was a potential change in follow-up for 71.7% of patients with one prior high-risk-HPV-positive result and 60.0% of patients with two or more prior high-risk HPV-positive results. There were 231 colposcopy reports evaluated in this study. Of these, 62 (26.8%) were abnormal colposcopy reports, including 45 low-grade squamous intraepithelial lesions, 15 high-grade squamous intraepithelial lesions, and two cancers. Twenty-five (40.3%) abnormal colposcopy findings were in patients with a history of at least than two prior HPV DNA-positive results and a report of currently being HPV-negative with the mRNA assay. The HPV mRNA assays are less sensitive for detection of latent HPV infections compared with HPV DNA assays. Based on these data and the potential change in follow-up care, the HPV mRNA assay should not be used for a primary screening tool for cervical cancer. Many pathology laboratories have shifted to using the HPV mRNA assay without clear discussion with gynecologists about the effects on patient follow-up. The type of HPV assay being used should be documented and any HPV mRNA result confirmed by HPV DNA assay.

Prevalence of High-Risk Human Papillomavirus in Tonsil Tissue in Healthy Adults and Colocalization in Biofilm of Tonsillar Crypts

The pathogenesis of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is currently an important topic of elucidation. The presence of latent HPV infection in tonsil tissue of healthy adults may provide an explanation for a component of this process and contribute to the understanding of HPV-associated squamous cell carcinoma oncogenesis of the oropharynx. To determine the prevalence of oropharyngeal HPV and to determine the spatial relationship between the virus and crypt biofilm in tonsil tissue. A retrospective, cross-sectional study was carried out using samples obtained from tonsils that were archived at a university hospital following elective nononcologic tonsillectomy from 2012 to 2015. Samples consisted of formalin-fixed paraffin embedded samples of tumor-free tonsil tissue from 102 adults between the ages of 20 and 39 years. Human papillomavirus status was assessed by polymerase chain reaction, and high-risk subtypes 16 and 18 were assessed with quantitative polymerase chain reaction assay. Samples that demonstrated presence of HPV were then analyzed by in situ hybridization to localize the viral capsid protein. These samples were then stained with concanavalin A to establish biofilm presence and morphology. These samples were also stained with diamidino-phenylindole (DAPI) to visualize location of the virus in relation to cell nuclei. These data were then assembled for aggregate analysis to colocalize HPV in the biofilm of the tonsillar crypts. Outcome measurements were determined prior to data collection and include prevalence of high-risk HPV types 16 and 18 in tonsil tissue of otherwise healthy adults, as well as demonstration with immunohistochemistry of HPV in tonsillar crypt biofilm. In 102 otherwise healthy adults (55 [53.9%] female; age range, 20-39 years), the overall prevalence of HPV in tonsils was 4.9% (n = 5); and high-risk type 16 or 18, 3.9% (n = 4). In this sample population, in situ hybridization colocalized HPV virus to the biofilm of the tonsillar crypts. Biofilm is present in the tonsillar crypts in a considerable proportion of tonsil tissues and may be reproducibly identified. Human papillomavirus is demonstrated to colocalize to the crypt biofilm. This has important implications with respect to the determination of HPV prevalence rates in the oropharynx. It may also play a role in the pathogenesis of HPV-related oropharyngeal carcinoma.

A study to assess expression of human papillomavirus types 16 and 18 in oral squamous cell carcinoma using polymerase chain reaction.

Objective:The diverse subset of oral squamous cell carcinoma (OSCC) with different clinical appearance and outcome, independent of traditional risk factors has led to increasing attention in human papillomavirus (HPV) infection.Materials and Methods:The investigation followed a case–control design. Information pertaining to the subjects was retrieved from hospital records. Twenty cases of OSCC and twenty age-matched controls were analyzed to ascertain the prevalence of HPV types 16 and 18. DNA was extracted from the blocks of formalin-fixed paraffin embedded tissues, and HPV-DNA was amplified using HPV type-specific primers by polymerase chain reaction (PCR) method. Data analysis was carried out using Chi-square test.Results:HPV-DNA was detected in 55% of cases (11/20; HPV 16 = 6, HPV 18 = 3 and HPV 16 and 18 = 2) and 30% of controls (6/20; HPV 16 = 3, HPV 18 = 1 and HPV 16 and 18 = 2) indicating higher percentage of HPV presence among OSCC cases. No significant association was found between the presence of HPV and gender, age, site and grade of differentiation of OSCC.Conclusion:Although the presence of HPV was higher in cases compared to controls, none of these differences were statistically significant. HPV 16 and 18 are commonly found in normal oral mucosa mandating the need for distinguishing clinical, subclinical and latent HPV infections.

ХАРАКТЕРИСТИКА IМУННОГО СТАТУСУ У ЖІНОК З ЛАТЕНТНОЮ ПАПІЛОМАВІРУСНОЮ ІНФЕКЦІЄЮ ШИЙКИ МАТКИ

Мета дослідження – аналіз змін показників, що характеризують стан імунітету, у жінок з генітальною латентною папіломавірусною інфекцією, часто поєднаною з урогенітальною інфекцією, на початку обстеження та через 6 місяців спостереження.Матеріали та методи. Обстежено жінок репродуктивного віку (від 18 до 45 років, 1200 осіб), що звернулись до гінекологічних відділень Перинатального центру та клінічної лікарні № 18 м. Києва за період з 2011 до 2016 рр. Контрольну групу склали 15 здорових жінок. Дослідження проведено за допомогою таких методів, як: цитологічний, кольпоскопічний, бактеріологічний, методу ПЛР, фенотипування лімфоцитів периферичної крові та статистичних методів.Результати дослідження та їх обговорення. При обстеженні 1200 жінок у 210 (16,0 %) виявлена ДНК вірусу папіломи людини (ВПЛ) за відсутності клінічних та морфологічних ознак інфекції, що свідчило про латентну папіломавірусну інфекцію (ПВІ). З них у 84 – діагностована моноінфекція, у 126 – поєднана папіломавірусна та урогенітальна інфекції (УГІ). Інфікування ВПЛ і вірогідність подальшого розвитку захворювання (елімінація або персистенція вірусу) значною мірою визначається клітинними та гуморальними факторами імунітету. Для з’ясування ролі імунної системи людини при латентній ПВІ проведено фенотипування лімфоцитів периферичної крові з використанням моноклональних антитіл та визначення рівня імуноглобулінів (Ig) А, М, G за методом радіальної імунодифузії на початку обстеження і через 6 місяців. У 140 жінок встановлена транзиторна ПВІ, у 70 – персистуюча.У жінок з латентною ПВІ шийки матки виявлені деякі ознаки вторинної імунної недостатності, що виражалось у зниженні відсотка Т-лімфоцитів та Т-хелперів з одночасним підвищенням кількості цитотоксичних лімфоцитів та природних кілерів (NK) на тлі активації гуморальної ланки імунітету. Супутня УГІ статевих органів підтримувала, а іноді і посилювала виявлені особливості імунореактивності при ПВІ. У жінок з транзиторною ПВІ спостерігалась нормалізація показників клітинного та гуморального імунітету, а подальша персистенція ВПЛ у шийці матки призводила до більш суттєвого пригнічення реакцій не тільки клітинної, а й гуморальної ланок імунітету (зниження кількості NK та імунорегуляторного індексу, рівня IgA).Висновок. Таким чином, у жінок з латентною ПВІ ШМ виявлялись деякі ознаки вторинної імунної недостатності, що виражалось у зниженні відсотку Т-лімфоцитів та Т-хелперів, з одночасним підвищенням кількості цитотоксичних лімфоцитів та природних кілерів на тлі активації гуморальної ланки імунітету.

Reactivation of Latent HPV Infections After Renal Transplantation.

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

Laryngopharyngeal reflux and herpes simplex virus type 2 are possible risk factors for adult-onset recurrent respiratory papillomatosis (prospective case-control study).

The human papillomavirus (HPV) causes recurrent respiratory papillomatosis (RRP). Although HPV prevalence is high, the incidence of papillomatosis is low. Thus, factors other than HPV infection probably contribute to RRP. This study investigated whether patients with papillomatosis are more often infected with herpes simplex virus type 2 and chlamydia trachomatis (ChT) and whether laryngopharyngeal reflux (LPR) occurs in this group of patients more often. Prospective case-control study. Department of Otorhinolaryngology of University Hospital. The study included 20 patients with adult-onset RRP and 20 adult patients with vocal cord cyst and no pathology of laryngeal mucosa (control group). Immunohistochemical analysis of pepsin, HPV, herpes simplex virus type 2 and ChT was performed in biopsy specimens of laryngeal papillomas and of healthy laryngeal mucosa (control group) obtained from medial part of removed vocal cord cyst during microlaryngoscopy procedures. Pathologic LPR (pepsin in tissue) was diagnosed in 8/20 (40.0%) patients with papillomatosis and in 0/20 control patients (P = .003). Herpes simplex virus type 2 was present in 9/20 (45.0%) patients with papillomatosis and in 0/20 control patients (P = .001). Five specimens were positive for both pepsin and herpes simplex virus type 2. No samples were positive for ChT. There were no significant differences between groups for age, body mass index, diabetes mellitus and gastrooesophageal reflux disease. Tobacco exposure was not more frequent in RRP group either (P = .01). Results show that LPR and herpes simplex virus type 2 are significantly more often present in patients with RRP. LPR and herpes simplex virus type 2 might activate latent HPV infection and thereby be possible risk factors for RRP.

Gardasil Vaccination for Recurrent Laryngeal Papillomatosis in Adult Men: First Report: Changes in HPV Antibody Titer

Patients with human papillomavirus (HPV) DNA-positive recurrent laryngeal papillomatosis commonly have repeated recurrences following surgery. The reason is suspected to be a mechanism by which latent HPV infection in the surrounding healthy mucosa reinfects the surgical site. It may be that production of HPV antibodies in the laryngeal mucosa with Gardasil injection could inhibit postoperative recurrence. This is a case series study. The purpose of this study was to examine whether Gardasil injection effectively inhibits recurrence. However, as a first report, we describe the antibody titers before and after vaccination. Gardasil was injected in 12 men (aged 32-74 years; mean age 47.9 years) with HPV-positive laryngeal papillomatosis. Serum antibody titers of HPV-6, -11, -16, and -18 were measured by a competitive Luminex-based immunoassay before the vaccination and 7 months after the start of the vaccination. Each of the antibody titers was very low before vaccination, and they rose in all patients after the vaccination. This finding demonstrates that antibody titers increase with Gardasil injection in post-adolescent males.

Adult-onset recurrent respiratory papillomatosis: a review of disease pathogenesis and implications for patient counseling.

A new diagnosis of adult-onset recurrent respiratory papillomatosis (AO-RRP) prompts many questions related to disease acquisition, course, and transmission. Recent attention to the human papillomavirus (HPV), along with emerging data on AO-RRP, provides a foundation for patient counseling. To provide a framework for these discussions, including an overview of the current literature on HPV-mediated disease across organs. The peer-reviewed literature was culled to provide a comprehensive review encompassing AO-RRP and anogenital papilloma, as well as general HPV virology and pathophysiology. PubMed and Google Scholar databases were searched from 1975 to July 2014. Most HPV infections in healthy adults are cleared within 2 years without clinical significance. Adult-onset RRP is a rare manifestation of HPV and may be homologous to anogenital HPV, which is highly transmissible between sexual partners. Horizontal transmission of AO-RRP has not been characterized. Our laboratory, however, recently found that nearly 100% of patients with AO-RRP had concurrent oral cavity HPV infection. Historically, an increased number of oral sex partners was thought to be associated with AO-RRP, but recent data from our group did not corroborate this finding. Recent data also question the dogma that smoking and laryngopharyngeal reflux play a role in recidivistic disease. Management of AO-RRP is often symptom based and includes lesion excision or ablation with adjuvant therapies including cidofovir for refractory cases. Recurrent respiratory papillomatosis may be related to a new or latent HPV infection, potentially obtained at birth, and the mechanism(s) underlying the progression from HPV infection to RRP remains unknown. Recommendations with regard to sexual practices in patients with AO-RRP cannot be made at this time. Unlike human immunodeficiency virus, patients with AO-RRP are not obligated to discuss infection status with partners. Despite the nebulous nature of the disease, clinicians should be a resource to discuss the current state of the literature with both the patient and partner.

Detection of oncogenic genital human papillomavirus (HPV) among HPV negative older and younger women after 7 years of follow-up

The knowledge on risk factors of being human papillomavirus (HPV)-positive among older women is sparse. The aim was to determine the frequency of oncogenic HPV appearance after 7 years among initially HPV-negative women and to examine potential risk factors that influence the occurrence of HPV in older women using multiple logistic regression. For comparison, a younger cohort of women examined under identical study settings was included. This prospective cohort study comprised 1,577 older women (age 40-50 at enrolment) and 2,920 women aged 22-32. Participants were interviewed and underwent a gynecological examination at two time points (7 years apart). Cervical samples were tested for HPV using Hybrid Capture 2 (HC2) and only women who tested HC2-negative at baseline were included. The HPV prevalence among older and younger women was 6.4% and 10.7%, respectively, and there was no "second peak" observed among older women. Recent sexual partners were a strong determinant of HPV appearance irrespective of age. Lifetime number of sexual partners was a significant risk factor for HPV appearance among older women, even after adjustment for recent sexual behavior. In addition, menopause was associated with a non-significantly increased risk of HPV appearance at follow-up. In conclusion, appearance of HPV in previously HPV-negative older women may be due to both recent sexual behavior and previous exposure that is, reactivation of a latent HPV infection.

PCR based detection of HPV 16 and 18 genotypes in normal oral mucosa of tobacco users and non-users

There is increasing evidence of a causal association between human papillomavirus (HPV) and oral squamous cell carcinoma (OSCC). Several studies have shown that HPV is associated with increased risk of oral cancer independent of exposure to tobacco and alcohol. The association is valid for HPVs 16 and 18, which generally are considered high risk types, because they have been detected in oral dysplastic lesions and cancers. We determined the baseline prevalence of HPVs 16 and 18 in normal oral mucosa of individuals with and without tobacco habit. PCR was used for DNA collected by oral smears to detect HPV 16/18 DNA in normal oral mucosa of 60 healthy individuals who were assigned to two groups of 30 subjects each. One group had a tobacco habit, the other did not. The tobacco user group comprised individuals who were tobacco chewers only. Sixty-five percent of individuals were positive for HPV 16/18 DNA, but HPV 16/18 positivity was less in individuals with tobacco habit than in those without tobacco habit. No significant association was found between the presence of HPVs and gender, age or duration of chewing habit, or between groups with and without a tobacco habit. We propose that HPVs16 and 18 commonly are present in normal oral mucosa and emphasize the importance of distinguishing clinical, subclinical and latent HPV infections when investigating HPVs and OSCC.

Ileostomy-Associated Chronic Papillomatous Dermatitis Showing Nevus Sebaceous–Like Hyperplasia, HPV 16 Infection, and Lymphedema

Chronic papillomatous dermatitis (CPD) is a stoma site complication due to chronic irritant contact dermatitis. Papillomatosis can also arise in the setting of human papillomavirus (HPV) infection or chronic lymphedema (elephantiasis). Herein, we report the case of a 57-year-old female who presented with a papillomatous growth surrounding a loop ileostomy suspected to be recurrent ovarian serous carcinoma. Excisional biopsy demonstrated nevus sebaceous (NS)-like organoid hyperplasia with koilocytes overlying a dermal scar that exhibited lymphangiectases. Polymerase chain reaction and sequencing for HPV DNA detected HPV 16. In situ hybridization for high-risk HPV DNA showed punctate nuclear pattern in the keratinocytes populating the NS-like hyperplasia indicating integrated HPV 16 DNA. No recurrence has been observed 11 months postexcision. Reports of CPD have documented a spectrum of reactive epidermal hyperplasias including pseudoepitheliomatous, verrucous, papillomatous, syringofibroadenomatous, and rudimentary follicular hyperplasias. HPV DNA has been detected in 3 of 4 CDP cases tested to date and in authentic NS. We postulate that localized lymphedema secondary to scarring coupled with chronic epidermal irritation and inflammation allowed for latent HPV infection to manifest as CPD with NS-like cutaneous hyperplasia.