Co-expression of low-risk HPV E6/E7 and EBV LMP-1 leads to precancerous lesions by DNA damage.

BACKGROUND: Low-risk human papillomavirus (HPV), such as types 6 and 11, is considered non-oncogenic, but these types have been detected in oral cancer tissue samples, suggesting their possible involvement in oral carcinogenesis. Because double infection of high-risk HPV and Epstein-Barr virus (EBV) is known to be involved in oral carcinogenesis, we hypothesized that low-risk HPV and EBV co-infection can transform the oral cells. To verify our hypothesis, we evaluated the transformation activity of cell lines expressing both low-risk HPV E6/E7 and EBV LMP-1. METHODS: We transduced HPV6, 11 and 16 E6/E7 genes and EBV LMP-1 gene into primary mouse embryonic fibroblasts. The cell lines were examined for indices of transformation activity such as proliferation, induction of DNA damage, resistance to apoptosis, anchorage-independent growth, and tumor formation in nude mice. To evaluate the signaling pathways involved in transformation, NF-κB and p53 activities were analyzed. We also assessed adhesion signaling molecules associated with anchorage-independent growth such as MMP-2, paxillin and Cat-1. RESULTS: Co-expression of low-risk HPV6 E6 and EBV LMP-1 showed increased cell proliferation, elevated NF-κB activity and reduced p53 induction. Moreover, co-expression of low-risk HPV6 E6 and EBV LMP-1 induced DNA damage, escaped from apoptosis under genotoxic condition and suppression of DNA damage response (DDR). Co-expression of low-risk HPV11 E6/E7 and EBV LMP-1 demonstrated similar results. However, it led to no malignant characteristics such as anchorage-independent growth, invasiveness and tumor formation in nude mice. Compared with the cells co-expressing high-risk HPV16 E6 and EBV LMP-1 that induce transformation, co-expression of low-risk HPV6 E6 and EBV LMP-1 was associated with low MMP-2, paxillin and Cat-1 expression. CONCLUSIONS: The co-expression of low-risk HPV E6/E7 and EBV LMP-1 does not induce malignant transformation, but it allows accumulation of somatic mutations secondary to increased DNA damage and suppression of DDR. Thus, double infection of low-risk HPV and EBV could lead to precancerous lesions.

Sex differences in the prevalence and determinants of HPV-related external genital lesions in young adults: a national cross-sectional survey in Brazil.

BACKGROUND: External genital lesions (EGL) are the most common sexually transmitted infections (STIs). We aimed to evaluate the prevalence, determinants and sex differences in EGL among young adults from Brazil. METHODS: Overall, 7694 participants (aged 16 to 25 years) underwent an interview, genital examination and sampling for HPV genotyping. RESULTS: The prevalence of EGL was 4.08% (234) and is more frequent in men (5.72%) than women (2.31%) (p <  0.001). Genital lesions were significantly associated with male sex, infection by high-risk and multiple HPV types, having more than two sexual partners in the last year, smoking status and the presence of other STI. While alcohol use was associated with a higher prevalence of EGL in women, same-sex sexual relationship increase the prevalence in men. In the EGL group, 67.79% (p = 0.032) were positive for HPV infection and the types HPV6 and HPV11 were the most prevalent ones. CONCLUSION: The prevalence of EGL in young adults was consistently high, and most cases were associated with genital HPV infection and STIs. Although men have a higher prevalence, both sexes share most genital lesion determinants. The promotion of sexual education and vaccination especially focus in young men, who are usually outside the targets of primary health care programmes, can prevent EGL in Brazilian young adults.

Prevalence and incidence of genital warts and cervical Human Papillomavirus infections in Nigerian women.

BACKGROUND: Genital warts are important causes of morbidity and their prevalence and incidence can be used to evaluate the impact of HPV vaccination in a population. METHODS: We enrolled 1020 women in a prospective cohort study in Nigeria and followed them for a mean (SD) of 9 (4) months. Nurses conducted pelvic examinations and collected ectocervical samples for HPV testing. We used exact logistic regression models to identify risk factors for genital warts. RESULTS: The mean age of study participants was 38 years, 56% (535/962) were HIV-negative and 44% (427/962) were HIV-positive. Prevalence of genital warts at enrolment was 1% (4/535) among HIV-negative women, and 5% (23/427) among HIV-positive women. Of 614 women (307 HIV negative and 307 HIV positive women) for whom we could compute genital wart incidence, it was 515 (95% CI:13-2872) per 100,000 person-years in HIV-negative and 1370 (95% CI:283-4033) per 100,000 person-years in HIV-positive women. HIV was associated with higher risk of prevalent genital warts (OR:7.14, 95% CI:2.41-28.7, p < 0.001) while higher number of sex partners in the past year was associated with increased risk of incident genital warts (OR:2.86, 95% CI:1.04-6.47. p = 0.04). HPV11 was the only HPV associated with prevalent genital warts in this population (OR:8.21, 95% CI:2.47-27.3, p = 0.001). CONCLUSION: Genital warts are common in Nigeria and our results provide important parameters for monitoring the impact of future HPV vaccination programs in the country. HIV infection and number of sexual partners in past year were important risk factors for prevalent and incident genital warts respectively.

Implication of low risk human papillomaviruses, HPV6 and HPV11 in laryngeal papillomatosis in Burkina Faso.

PURPOSE: Laryngeal papillomatosis is the most common benign tumor of the larynx of children. It is characterized by the development of exophytic proliferative lesions in the mucosa of the airways. Human papillomavirus (HPV) has been recognized as a causal agent among which HPV types 6 and 11 are the most frequently implicated. This disease affects the vocal cords and other important functions of the child. The difficulty of treatment is related to the high recurrence of papilloma growth after surgical removal. The objective of this study was to describe the implication of HPV6 and HPV11 in cases of laryngeal papillomatosis histologically confirmed in Ouagadougou. MATERIALS AND METHODS: This was a descriptive cross-sectional study based on histologically diagnosed archival tissue; obtained in the last ten years (2007 to 2017) in the anatomy and cyto-pathology laboratories in Burkina Faso. These fixed and paraffin-embedded tissues were deparaffinized with xylene before HPV DNA extraction; then HPV6 and HPV 11 were identified by real-time multiplex PCR. RESULTS: The prevalence of low-risk HPV infection (HPV-LR) was 54.84% in histologically confirmed laryngeal papillomatosis in Ouagadougou. Among the HPV-LR positive samples, HPV6 and HPV11 genotype prevalence's were respectively 41.17% and 35.3% while the HPV6 / HPV11 co-infection was 23.53%. CONCLUSIONS: The results show the implication of HPV6 and HPV11 in laryngeal papillomatosis in Burkina Faso with a high prevalence.

Role of histological findings and pathologic diagnosis for detection of human papillomavirus infection in men.

Early HPV infection in males is difficult to detect clinically and pathologically. This study assessed histopathology in diagnosing male genital HPV. External genital lesions (n = 352) were biopsied, diagnosed by a dermatopathologist, and HPV genotyped. A subset (n = 167) was diagnosed independently by a second dermatopathologist and also re-evaluated in detail, tabulating the presence of a set of histopathologic characteristics related to HPV infection. Cases that received discrepant diagnoses or HPV-related diagnoses were evaluated by a third dermatopathologist (n = 163). Across dermatopathologists, three-way concordance was fair (k = 0.30). Pairwise concordance for condyloma was fair to good (k = 0.30-0.67) and poor to moderate for penile intraepithelial neoplasia (k = -0.05 to 0.42). Diagnoses were 44-47% sensitive and 65-72% specific for HPV 6/11-containing lesions, and 20-37% sensitive and 98-99% specific for HPV 16/18. Presence of HPV 6/11 was 75-79% sensitive and 35% specific for predicting pathologic diagnosis of condyloma. For diagnosis of penile intraepithelial neoplasia, HPV 16/18 was 95-96% specific but only 40-64% sensitive. Rounded papillomatosis, hypergranulosis, and dilated vessels were significantly (P < 0.05) associated with HPV 6/11. Dysplasia was significantly (P = 0.001) associated with HPV 16/18. Dermatopathologists' diagnoses of early male genital HPV-related lesions appear discordant with low sensitivity, while genotyping may overestimate clinically significant HPV-related disease. Rounded papillomatosis, hypergranulosis, and dilated vessels may help establish diagnosis of early condyloma.

Human papillomavirus and cervical cancer.

Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and clears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16, 18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved.

Recombination-dependent oligomerization of human papillomavirus genomes upon transient DNA replication.

We describe the extensive and progressive oligomerization of human papillomavirus (HPV) genomes after transfection into the U2OS cell line. The HPV genomic oligomers are extrachromosomal concatemeric molecules containing the viral genome in a head-to-tail orientation. The process of oligomerization does not depend on the topology of the input DNA, and it does not require any other viral factors besides replication proteins E1 and E2. We provide evidence that oligomerization of the HPV18 and HPV11 genomes involves homologous recombination. We also demonstrate oligomerization of the HPV18 and HPV11 genomes in SiHa, HeLa, and C-33 A cell lines and provide examples of oligomeric HPV genomes in clinical samples obtained from HPV-infected patients.

Laser capture microdissection shows HPV11 as both a causal and a coincidental infection in cervical cancer specimens with multiple HPV types.

AIMS: To identify, by laser capture microdissection (LCM), the cellular localization of HPV11 when present with carcinogenic HPV in invasive cervical cancer (ICC) specimens, and to relate this to p16(INK) (4a) expression. METHODS AND RESULTS: Three squamous cell ICC specimens showing coinfection with HPV11 and carcinogenic HPV16 or HPV31 were selected from the Institut Català d'Oncologia international survey of anogenital carcinomas, and coinfection was confirmed by SPF10 -DEIA-LiPA25 analysis. In two cases LCM-PCR identified HPV11 in low-grade and high-grade squamous intraepithelial lesions (SILs) adjacent to the ICC, and HPV16 or HPV31 in the ICC. In one case, HPV11 was the only genotype found in the ICC. P16(INK) (4a) expression was diffuse in ICC associated with carcinogenic HPV, but focal in ICC with HPV11. CONCLUSIONS: Our results confirm that a single cervical, cancerous or precancerous lesion is associated with a single HPV type. Detecting low-risk HPV as a coinfection in whole tissue from ICC does not prove a causal association. HPV11 may be found only in an adjacent SIL with carcinogenic HPV in the ICC. It is also found alone in carcinoma. LCM-PCR and differential P16(INK) (4a) expression can clarify the causal role of each type when multiple HPVs are present in whole tissue from carcinomas.

Genomic differences in the background of different severity in juvenile-onset respiratory papillomatoses associated with human papillomavirus type 11.

This study aimed to compare complete genome sequences of human papillomavirus (HPV) type 11 from two solitary papillomas (considered minimally aggressive), two moderately (six and nine episodes) and two highly aggressive (30 and 33 episodes) juvenile-onset respiratory papillomatoses. Genomic regions were sequenced using the Sanger method; sequences were compared to available GenBank genomes. Activity of the long control region (LCR) was assessed in HEp-2 cell line using luciferase assays and compared to that of the reference (GenBank Accession Number M14119). Site-directed mutagenesis was performed to confirm the association of polymorphisms with differences in LCR activity. Eleven alterations resulted in amino acid changes in different open reading frames. A72E in E1 and Q86K in E2 proteins were exclusively present in a moderately aggressive disease, L1 alterations A476V and S486F were unique to a severe papillomatosis. HPV11s in both solitary papillomas had identical LCRs containing a T7546C polymorphism, which strongly attenuated LCR activity, as confirmed by site-directed mutagenesis. This strong attenuator polymorphism was also present in the other four genomes showing significantly higher activities, but in these other alterations with demonstrable but statistically not significant attenuating (A7413C, 7509 T deletion) or enhancing (C7479T, T7904A) effect on transactivating potential (as demonstrated by site-directed mutagenesis) were also detected. LCR activities corresponded well to severity, excepting the highly aggressive papillomatosis with the L1 alterations. Presence of intratypic variants cannot explain differences in severity of respiratory papillomatoses associated with HPV11; virulence seems to be determined by the interaction of multiple genetic differences.

Nonconserved lysine residues attenuate the biological function of the low-risk human papillomavirus E7 protein.

The mucosotrophic human papillomaviruses (HPVs) are classified as high-risk (HR) or low-risk (LR) genotypes based on their neoplastic properties. We have demonstrated previously that the E7 protein destabilizes p130, a pRb-related pocket protein, thereby promoting S-phase reentry in postmitotic, differentiated keratinocytes of squamous epithelia, and that HR HPV E7 does so more efficiently than LR HPV E7. The E7 proteins of LR HPV-11 and -6b uniquely possess lysine residues following a casein kinase II phosphorylation motif which is critical for the biological function of E7. We now show that mutations of these lysine residues elevated the efficiency of S-phase reentry, independent of their charge. An 11E7 K39,42R mutation moderately increased the association with and the destabilization of p130. Unexpectedly, polyubiquitination on these lysine residues did not attenuate E7 activity, as their mutation caused elevated proteasomal degradation and decreased protein stability. In this regard, the biologically more potent HR HPV E7 proteins were also less stable than the LR HPV E7 proteins. We infer that these lysine residues impede functional protein-protein interactions. A G22D mutation of 11E7 at the pocket protein binding motif possessed augmented efficiency in promoting S-phase reentry and strongly enhanced association with p130 and pRb. The combined effects of these two classes of 11E7 mutations exhibited an efficiency of S-phase reentry comparable to that of HR HPV E7. Thus, these nonconserved residues are primarily responsible for the differential abilities of LR and HR HPV E7 proteins to promote unscheduled DNA replication in organotypic raft cultures.

Melanosis of the vagina and human papillomavirus infection, an uncommon pathology: case report.

Benign melanotic lesions of the vagina are uncommon and only a few cases have been reported in the literature. A 34-year-old woman was referred because of a Vaginal Intraepithelial Neoplasia 1 biopsy result. On the gynecological examination, two different hyperpigmented areas were noted in the vagina. The colposcopic visualization of the cervix and vagina found an aceto-white lesion at the right lateral wall of the upper third of the vagina. Biopsies from three areas were taken. Histological study reported a melanosis of the vagina and HPV infection. An immunohistochemical panel of epithelial markers was performed in vaginal samples, such as Cytokeratin AE1/AE3 and epithelial membrane antigen, mesenchymal marker: vimentin; melanocytic makers: protein S-100 and HMB45 (Human Melanoma Black); proliferating cell marker: proliferating cell nuclear antigen (PCNA), and P-53 oncoprotein. High Risk (16, 18, 31, 45) and Low Risk (6, 11) HPV types were studied by In Situ Hybridization using the same vaginal samples. CK, EMA and Vimentin were 2+. Melanocytic markers, HMB45 and S100, and PCNA were 1+ in basal cell layer. P-53 was negative. The melanotic tissue and acetowhite lesion were positives to HPV Types 6,11. In conclusion, melanosis of the vagina is a uncommon benign pathology. Usually, melanosis is present in women over 40 years old. We present a case of melanosis of the vagina in a young woman infected with low-risk HPV types and review the literature.

Prevalence and sociodemographic correlates of anogenital Human Papillomavirus (HPV) carriage in a cross-sectional, multi-ethnic, community-based Asian male population.

BACKGROUND: Addressing the burden of HPV-associated diseases among men is increasingly becoming a public health issue. The main objective of this study was to determine HPV prevalence among a healthy community-based Malaysian men. METHOD: This was a cross-sectional study that recruited 503 healthy males from 3 community-based clinics in Selangor, Malaysia. Genital and anal samples were collected from each participant for 14 high risk and 2 low risk HPV DNA detection and genotyping. All participants responded to a set of detailed sociodemographic and sexual behaviour questionnaire. RESULTS: The median age at enrolment was 40 years old (IQR: 31-50). The anogenital HPV6/11 prevalence was 3.2% whereas high risk HPV prevalence was 27.1%. The genital HPV prevalence for HPV6/11 was 2.9% while high risk HPV was 18.8%. HPV6/11 prevalence in the anal canal was 1.6% and high risk HPV was 12.7%. HPV 18 was the most prevalent genotype detected in the anogenital area. There was a significant independent association between genital and anal HPV infections. CONCLUSION: Anogenital HPV infection is common among Malaysian men. These findings emphasize the ubiquity of HPV infection and thus the value of population-wide access to HPV prevention.

Autophagy is induced in human keratinocytes during human papillomavirus 11 pseudovirion entry.

Human papillomavirus type 11 (HPV11) is one of the main causes of condyloma acuminatum, a widespread sexually transmitted disease. During infection of its primary target cell, keratinocytes, it is likely to encounter the autophagy pathway, which is an intracellular maintenance process that is also able to target invading pathogens. It is currently unknown whether HPV11 is targeted by autophagy or whether it is able to escape autophagy-mediated killing. Here, we investigated the autophagy response during HPV11 pseudovirion (PsV) entry in human keratinocytes. Transmission electron microscopy showed that intracellular PsVs were sequestered in lumen of double-membrane autophagosomes that subsequently appeared to fuse with lysosomes, while confocal microscopy showed induction LC3 puncta, the hallmark of induced autophagy activity. Furthermore, quantitative infection assays showed that high autophagy activity resulted in reduced HPV11 PsV infectivity. Therefore, the autophagy pathway seemed to actively target invading HPV11 PsVs for destruction in the autolysosome. Western analysis on the phosphorylation state of autophagy regulators and upstream pathways indicated that autophagy was activated through interplay between Erk and Akt signaling. In conclusion, autophagy functions as a cellular protection mechanism against intracellular HPV11 and therefore therapies that stimulate autophagy may prevent recurrent condyloma acuminatum by helping eliminate latent HPV11 infections.

Immune dysregulation and tumor-associated gene changes in recurrent respiratory papillomatosis: a paired microarray analysis.

Recurrent respiratory papillomas (RRP) are benign airway tumors, caused primarily by human papillomaviruses (HPV) types 6 and 11. The disease is characterized by multiple recurrences after surgical removal, with limited effective therapy. To identify novel targets for future therapy, we established transcriptional profiles for actively growing papillomas compared with autologous, clinically normal, laryngeal epithelia (adjacent tissue). Total ribonucleic acid (RNA) from 12 papillomas and 12 adjacent tissues were analyzed by microarray, and the matched sets of tissues compared by paired t test, to identify differentially expressed genes in papilloma tissues while minimizing variations intrinsic to individual patients. Quantitative polymerase chain reaction (PCR) was used to confirm the relative expression levels for a subset of genes. Within the 109 differentially expressed transcripts whose expression varied at least three-fold were two large groups of genes with related functions. The first group consisted of 18 genes related to host defense, including both innate and adaptive immunity. The second group contained 37 genes that likely contribute to growth of papillomas as benign tumors, since the altered pattern of expression also had been reported previously in many cancers. Our results support our previous studies that document a systemic T(H)2-like adaptive immune response in RRP, and suggest that there is a role for altered innate immunity in RRP as well. We propose that HPV 6 and 11 infection establishes a tumorigenic microenvironment characterized by alteration of both innate inflammatory signals and adaptive immune responses that prevent effective T(H)1-like response, in conjunction with altered expression of numerous genes that regulate cellular growth and differentiation.

Identification of human papillomavirus in esophageal squamous papillomas.

AIM: To investigate the presence of human papillomavirus (HPV) in esophageal squamous papilloma (ESP) and determine p16, p53 and Ki67 expression in a Mexican cohort. METHODS: Nineteen cases diagnosed as ESP, corresponding to 18 patients were reviewed; nineteen cases of normal esophageal mucosa were used as negative controls. HPV detection was performed by amplified chromogenic in situ hybridization (ACISH) using a wide spectrum-cocktail probe and PCR. RESULTS: The average age at presentation was 46.3 years (range 28-72 years). Patients included four (22.22%) males and 14 (77.77%) females. The most frequent location was upper third (11 cases), followed by middle third (3 cases) and unknown site (5 cases). Immunohistochemistry (IHC) revealed basal and focal p53 expression in 17 cases (89%); p16 was expressed in eight cases (42.10%) and the Ki67 index ranged from 10% to 30%. HPV was detected in 14 out of 16 cases (87.5%) by ACISH: Twelve showed diffuse nuclear patterns and two showed granular patterns. HPV DNA was identified by PCR in 12 out of 14 cases (85.7%). Low-risk HPV types were detected in the most of the cases. CONCLUSION: This study provides identification of HPV infection in almost 80% of ESP using either ACISH or PCR; overall, all of these lesions show low expression of cell-cycle markers. We suggest ACISH as an alternative diagnostic tool for HPV detection in ESP.

Development of a human papillomavirus type 6/11 vaccine candidate for the prevention of condyloma acuminatum.

Condyloma acuminatum (CA) represents a significant human papillomavirus (HPV) disease burden worldwide, resulting in substantial healthcare costs and loss of life quality in both genders. To address this problem, we tried to develop a bivalent HPV6/11 virus-like particle (VLP) vaccine targeting CA. HPV6/11 VLPs were generated in Hansenula polymorpha, and a disassembly and reassembly (D/R) treatment was further conducted to improve the stability and monodispersity of the VLPs. The HPV6/11 VLPs were identified by transmission electron microscopy (TEM), high performance liquid chromatography (HPLC), mass spectrum (MS) and dynamic light scattering (DLS), and were evaluated for their immunogenicity in both mice and cynomolgus monkeys. The results showed that the HPV6/11 L1 proteins were correctly expressed and assembled into HPV6/11 VLPs, and the HPV6/11 VLPs formulated with aluminum phosphate induced vigorous production of specific neutralizing antibodies against HPV6/11 VLPs in mice and cynomolgus monkeys. These data indicated that the Hansenula polymorpha-derived HPV6/11 VLPs could be formulated into a bivalent vaccine used in prevention of CA.

Recurrent respiratory papillomatosis: A state-of-the-art review.

Recurrent respiratory papillomatosis (RRP) is a benign disease of the upper aero-digestive tract caused by human papillomavirus (HPV) infection, which affects children and young adults. The aim of this review is to describe the main etiological, epidemiological, clinical, diagnostic, and treatment aspects of RRP. Most infections in children occur at birth, during passage through the birth canals of contaminated mothers. In adults, HPV is transmitted sexually. Papillomas usually appear as exophytic nodules, primarily in the larynx, but occasionally involving the nasopharynx, tracheobronchial tree, and pulmonary parenchyma. The disease course is unpredictable, ranging from spontaneous remission to aggressive persistent or recurrent disease. Although it occurs rarely, RRP has the potential for malignant transformation to squamous cell carcinoma. Clinically, RRP usually presents with nonspecific symptoms of airway involvement, including chronic cough, hoarseness, wheezing, voice change, stridor, and chronic dyspnea. Helical computed tomography (CT) is highly accurate for the identification and characterization of focal or diffuse airway narrowing caused by nodular vegetant lesions. The typical CT pattern of lung papillomatosis consists of numerous multilobulated nodular lesions of various sizes, frequently cavitated, scattered throughout the lungs. Bronchoscopy is the most reliable method for the diagnosis of RRP; it enables direct visualization of lesions in the central airways and collection of biopsy samples for histopathological diagnosis, and is also useful for therapeutic planning. The definitive diagnosis of RRP is based on histopathological analysis. Currently, no definitive curative treatment for RRP is available; despite the availability of adjunctive treatments, surgery remains the mainstay of treatment.

Number of external anogenital warts is associated with the occurrence of abnormal cervical cytology.

BACKGROUND: Anogenital warts (AGWs) are common results of sexually transmitted infection (STI). Human papillomavirus (HPV) types 6 and 11, which are non-oncogenic types, account for 90% of the clinical manifestations. Although the quadrivalent HPV vaccine has been launched, AGW remains prevalent in some countries and shows association with abnormal cervical cytology. OBJECTIVES: To study the prevalence of abnormal cervical cytology (low grade squamous intraepithelial lesions or worse; LSIL+) in immunocompetent Thai women newly presenting with external AGWs. MATERIALS AND METHODS: Medical charts of all women attending Siriraj STI clinic during 2007-2011 were reviewed. Only women presenting with external AGWs who were not immunocompromised (pregnant, human immunodeficiency virus positive or being on immunosuppressant drugs) and had not been diagnosed with cervical cancer were included into the study. Multivariate analysis was used to determine the association between the characteristics of the patients and those of AGWs and LSIL+. RESULTS: A total of 191 women were eligible, with a mean age of 27.0±8.9 years; and a mean body mass index of 20.6±8.9 kg/m2. Half of them finished university. The most common type of AGWs was exophytic (80.1%). The posterior fourchette appeared to be the most common affected site of the warts (31.9%), followed by labia minora (26.6%) and mons pubis (19.9%). The median number of lesions was 3 (range 1-20). Around 40% of them had recurrent warts within 6 months after completing the treatment. The prevalence of LSIL+ at the first visit was 16.3% (LSIL 12.6%, ASC-H 1.1%, HSIL 2.6%). After adjusting for age, parity and miscarriage, number of warts ≥ 5 was the only factor associated with LSIL+ (aOR 2.65, 95%CI 1.11-6.29, p 0.027). CONCLUSIONS: LSIL+ is prevalent among immunocompetent Thai women presenting with external AGWs, especially those with multiple lesions.

Quadrivalent HPV vaccine efficacy against disease related to vaccine and non-vaccine HPV types in males.

A small number of HPV types are related to a majority of HPV-related neoplastic lesions in humans. High-risk types such as HPV 16 and 18 are most often implicated, although other oncogenic and non-oncogenic HPV types can cause disease in men. The efficacy of the quadrivalent HPV vaccine (qHPV) against external genital lesions and intra-anal disease related to HPV in men has been demonstrated. This report examines the vaccine's efficacy against disease due to 10 additional non-vaccine HPV types, as well as efficacy regardless of HPV detection. The data presented suggest that vaccinating males against HPV 6, 11, 16 and 18 protects them against most vaccine HPV-type related anogenital disease. However, significant efficacy against disease due to non-vaccine HPV types was not seen. In addition, the data do not provide any evidence that vaccination with qHPV vaccine will increase the likelihood of disease caused by non-vaccine types in the short term.