Low-risk Human Papillomavirus Subtypes Research Articles

Characterization of HPV subtypes in invasive cervical cancer in Botswana patients using a pan-pathogen microarray technology

Human papillomavirus (HPV) plays a significant role in the development of cervical cancers in the setting of co-infection with HIV. Botswana has a high prevalence of HIV and cervical cancer. In this study, we investigated the distribution of HPV subtypes in cervical cancer biopsy samples from patients in Botswana using a highly sensitive pan-pathogen microarray technology, PathoChip, to detect both high- (HR-HPV) and low-risk HPV (LR-HPV) subtypes in women living with HIV (WLWH) and women living without HIV. We analyzed samples from 168 patients, of which 73% (n = 123) were WLWH with a median CD4 count of 479.5 cells/μL. Five HR-HPV subtypes were detected in the cohort: HPV 16, 18, 26, 34, and 53. The most prevalent subtypes were HPV 26 (96%) and HPV 34 (92%); 86% of WLWH (n = 106) had co-infection with four or more HR-HPV subtypes compared to 67% (n = 30) of women without HIV (p < 0.01). We detected 66 LR-HPV subtypes among all cervical cancer patients, with HPV 6b and 48 being most prevalent. Notably, signatures for LR-HPV subtypes 10, 41, 90, and 129 were only detected in WLWH. Signal intensity for HPV 18 was significantly weaker in WLWH with CD4 levels ≤200 cells/μL as compared to patients with >200 cells/μL and HIV-negative patients. Although the majority of cervical cancer specimens in this cohort were determined to have multiple HPV infections, the most prevalent HR-HPV subtypes (HPV 26 and HPV34) found in these cervical cancer samples are not covered in the current HPV vaccines. Though no conclusions can be made on the direct carcinogenicity of these subtypes the results do underlie the need for continued screening for prevention of cervical cancer.

High-risk human papillomavirus 16/18 associated with improved survival in sinonasal squamous cell carcinoma.

There has been conflicting evidence on the independent prognostic role of human papillomavirus (HPV) status in sinonasal cancer. The objective of this study was to assess whether the survival of patients with sinonasal cancer differs based on various HPV statuses, including HPV-negative, positive for the high-risk HPV-16 and HPV-18 (HPV16/18) subtypes, and positive for other high-risk and low-risk HPV subtypes. In this retrospective cohort study, data from the National Cancer Database were extracted from the years 2010-2017 for patients who had primary sinonasal cancer (N = 12,009). The outcome of interest was overall survival based on HPV tumor status. Study included an analytic cohort of 1070 patients with sinonasal cancer who had confirmed HPV tumor status (732 [68.4%] HPV-negative; 280 [26.2%] HPV16/18-positive; 40 [3.7%] positive for other high-risk HPV; and 18 [1.7%] positive for low-risk HPV). HPV-negative patients had the lowest all-cause survival probability at 5 years postdiagnosis (0.50). After controlling for covariates, HPV16/18-positive patients had a 37% lower mortality hazard than HPV-negative patients (adjusted hazard ratio, 0.63; 95% confidence interval [CI], 0.48-0.82). Patients aged 64-72 years (crude prevalence ratio, 0.66; 95% CI, 0.51-0.86) and 73 years and older (crude prevalence ratio, 0.43; 95% CI, 0.31-0.59) presented with lower rates of HPV16/18-positive sinonasal cancer than those aged 40-54 years. In addition, Hispanic patients had a 2.36 times higher prevalence of non-HPV16/18 sinonasal cancer than non-Hispanic White patients. These data suggest that, for patients with sinonasal cancer, HPV16/18-positive disease may confer a significant survival advantage compared with HPV-negative disease. Other high-risk and low-risk HPV subtypes have survival rates similar to the rates for HPV-negative disease. HPV status might be an important independent prognostic factor in sinonasal cancer that could be used in patient selection and clinical decisions.

The Prevalence of High- and Low-Risk Types of HPV in Patients with Squamous Cell Carcinoma of the Head and Neck, Patients with Chronic Tonsillitis, and Healthy Individuals Living in Poland.

Human papillomavirus (HPV) is a virus with the potential to infect human epithelial cells and an etiological agent of many types of cancer, including head and neck cancer. The aim of the study was to determine the prevalence of HPV infection in patients with head and neck squamous cell carcinoma (HNSCC), patients with chronic tonsillitis, and healthy individuals, and to establish high- and low-risk HPV genotypes in these groups. The objectives also comprised the delineation of the relationship between the infection with high- or low-risk HPV subtypes and clinicopathological and demographic characteristics of the study groups. This study was composed of 76 patients diagnosed with HNSCC, 71 patients with chronic tonsillitis, and 168 cases without either of these conditions (the control group). HPV detection and identification of subtypes were performed on isolated DNA using a test which allowed detection of 33 common high-risk and low-risk HPV subtypes. The prevalence of HPV infection was 42.1%, 25.4%, and 37.5% in HNSCC, chronic tonsillitis, and control groups, respectively. HPV 16 was the most prevalent genotype in all groups and the non-oncogenic HPV 43/44 was frequent in HNSCC patients. This analysis provides insight into the prevalence of oral oncogenic and non-oncogenic HPVs in patients with head and neck cancer, patients with chronic tonsillitis and healthy individuals, and leads to the conclusion that further investigations are warranted to examine a larger cohort of patients focusing on high- and low-risk HPV genotypes. Efforts should be focused on screening and prevention strategies, and therefore, it is important to introduce tools for effective detection of HPV genotypes. Furthermore, given the role of vaccines against oral HPV infection, our observations lead to the suggestion that HPV vaccination should be of considerable importance in public health strategies.

Human Papilloma Virus Distribution Across the African Diaspora.

PURPOSEUnderstanding the distribution of human papilloma virus (HPV) subtypes in limited-resource settings is imperative for cancer prevention strategies in these regions. The objective of our study is to compare the prevalence of cervical HPV genotypes in women across the African diaspora.METHODSThis study was approved by the African Caribbean Consortium (AC3). Six member institutions (Benin, Ethiopia, The Bahamas, Tobago, Curacao, and Jamaica) provided independently collected HPV data. Prevalence comparisons across for each nation were performed followed by an assessment of anticipated 9-valent vaccine coverage. Chi-square or Fisher's exact tests were used with significance at P < .05.RESULTSOne thousand three hundred fifty high-risk (HR) and 584 low-risk (LR) HPV subtypes were identified in the entire cohort. The most common HR HPV subtype was HPV 16 (17.9%) of infections. The distribution of HR and LR subtypes varied by country. The proportion of HR-HPV subtypes covered by the current 9-valent vaccine was lower in African countries compared with the Caribbean countries (47.9% v 67.9%; P < .01). No significant difference was seen for LR subtypes (8.1% African continent v 5.2% Caribbean; P = .20). Marked variation in the proportion of infections covered by the 9-valent vaccine persisted in individual countries.CONCLUSIONSignificant variations in HPV prevalence were identified among African and Afro-Caribbean women. A large number of women in these regions are potentially uncovered by current vaccination formulation, particularly low-risk HPV infections.

Orthokeratinized odontogenic cysts: a Spanish tertiary care centre study based on HPV DNA detection

BackgroundThe role of human papillomavirus (HPV) in orthokeratinized odontogenic cysts (OOCs) has rarely been studied. The objective is to describe the clinicopathological findings in a series of OOCs from a Spanish population that were investigated in relation to the possible presence of HPV.MethodsA clinicopathological retrospective analysis followed by a molecular analysis of 28 high- and low-risk HPV genotypes was performed in OOC samples of patients seen during the last 15-years in a Spanish tertiary care center.ResultsOf 115 odontogenic cysts with keratinization, 16 cases of OOCs were confirmed and evaluated. OOCs occurred predominantly in the mandible of males (mean age 36.06 ± 13.16 years). Swelling of the jaw followed by pain were the most common clinical symptoms, and 56.5% of the OOC cases were associated with an unerupted tooth. After a mean post-cystectomy follow-up of 3.8 years, only one recurrent case was observed, resulting in a verrucous cystic lesion that was considered premalignant after immunohistological examination. DNA extraction was successful from 14 of the 16 OOC cases. None of the primary OCCs or the single recurrent OOC were positive for HPV in the molecular analysis.ConclusionsOOCs show a very limited potential for recurrence. Our results suggest that neither high- or low-risk HPV subtypes are likely to play a role in the etiology or neoplastic transformation of OOC, at least in the Spanish population.

Distribution of human papillomavirus genotypes (2014–2016) in women with genital warts at a sexually transmitted disease clinic in Beijing, China

Aim: The aim of this study was to analyze the distribution of human papillomavirus (HPV) genotypes among women with genital warts in the Beijing region of China. Methods: A total of 350 women diagnosed with genital warts between 2014 and 2016 were analyzed by real-time polymerase chain reaction (PCR) to test for high-risk and low-risk HPV subtypes. Results: The results show that 52.6% (184/350) of cases were positive for HPV6+11. The three most common high-risk HPVs detected were HPV52, HPV16 and HPV58, detected in 12.0% (42/350), 10.6% (37/350) and 10.0% (35/350) of all cases, respectively. Conclusion: These results indicate that vaccines targeting HPV subtypes 6, 11, 16, 52 and 58 would have the greatest impact among sexually active women living in Beijing.

Retrospective Analysis of Prevalence of High-risk and Low-risk Human Papillomavirus (HPV) Genotypes in Iranian Women During 2013-2016

Background and objective: Considering the importance of HPV in cancer etiology, awareness of HPV prevalence and frequency of high-risk genotypes could help improve health care system management. We analyzed HPV prevalence in women forms different provinces of Iran that is the largest sample till now. Material and Methods: In this retrospective cross-sectional study, 2969 outpatient and suspicious women aged 17- 78 referred to Noor pathobiology laboratory from 24 provinces of Iran were studies. DNA extraction and PCR were performed on samples and then HPV genotypes were also determined using hybridization kit. Results: HPV DNA was detected in 29.3% of valid liquid-based samples. Among HPV positive cases, 67.2% and 52.0% accounted for high-risk and low-risk HPV subtypes, respectively. In patients with high-risk HPV types, HPV16 was confirmed as predominate type (30.5%) followed by HPV53 (17.3%) and HPV39 (13.3 %). HPV6 was found as the most common low-risk HPV type with 60.6% frequency rate followed by HPV11 (17.9%) and HPV81 (8.6%) in this age group. It was apparent that age group &gt;25 years accounted the highest frequency of HPV positivity. The prevalence of HPV was significantly different among different age groups (p&lt;0.0001). Conclusion: It can be concluded that HPV infection is currently at a considerable high level in Iran. Looking at the high risk and oncogenic HPV subtypes frequency especially in younger age groups, a concern could be noticed about HPV relevant cancers which can be prevented by commercial and approved HPV vaccines.

Single and multiple high-risk and low-risk Human Papillomavirus association with cervical lesions of 11,224 women in Jakarta.

We sought to evaluate prevalence, age-adjusted distribution, and impact of single and multiple high- and low-risk human papillomavirus (HPV) subtypes and their associations with cervical lesions. Data were extracted from 11,224 women who underwent routine screening of HPV genotyping and liquid-based cytology co-testing. Fifteen high-risk (HR) and six low-risk (LR) HPV types were genotyped. Overall HPV prevalence was 10.7%, and young women (under 21years old) harbored highest HPV infection rate (40.38%). The rate declined in old women 9.49% (age 30-49) and 6.89% (age 50 and above). Normal cytology had lowest HPV (5.66%) compared to low-grade (60.49%), high-grade (71.96%) squamous intraepithelial lesions (LSIL and HSIL) and squamous cell carcinoma SCC (86.9%). LR HPV subtypes were absent in SCC and were consistently lower than HR HPV in LSIL (6.74 vs. 33.54%) and HSIL (2.12 vs. 51.32%). Multiple HPV infection was more frequent in young women under 30years old (10%) than older women (2%) and in LSIL (20.2%), HSIL (18.5%) than SCC (4.4%). HR HPV52, 16, 18, and 58 were the most frequent subtypes in normal, LSIL, and HSIL. Greater or equal proportion of HPV 16, 18, 45, and 52 was found in SCC compared to normal cytology (SCC/normal ratios 4.8, 1.2,1.6, and 1.7). While important in LSIL and HSIL, HPV58 was not detected in SCC. Taken together, identification of these HPV types, especially HPV 16, 18, 45, and 52, and their associated cervical lesions may improve cervical cancer preventive strategies in Indonesia.

Analysis of Human Papillomavirus Infection in 16,320 Patients From a Gynecology Clinic in Central South China.

This study aimed to investigate the relationship between persistent human papillomavirus (HPV) infection and cervical lesion. Clinical data of 16,320 patients who visited our clinic between January 2009 and December 2013 were collected. Retrospective analysis was performed to analyze the overall HPV infection and compare the infection rates of different subtypes among different age groups, to reveal the relationship between persistent HPV infection and cervical cytology. The overall prevalence of HPV was 26.54%. The most common genotypes were HPV 52, HPV 16, HPV 58, CP8304, and HPV 53. The highest overall high-risk HPV prevalence was found in women older than 60 years, and the lowest prevalence was found in women between the ages of 30 and 39 years. There was no significant difference in low-risk HPV prevalence among different age groups (p = .693). The HPV clearance rate after 1 year among those with initial positive test was 87.65%. The constituent ratios of high- or low-risk HPV subtypes were not significantly different (p = .545) between nonpersistent-positive and persistent-positive (PP) groups. Conversely, the constituent ratios of singe- or multi-type HPV infection were significantly different (p < .05) between these 2 groups. The most common subtypes in PP group were HPV 16, 52, 58, CP8304, and 33. The occurrence rates of atypical squamous cells of undetermined significance, high-grade squamous intraepithelial lesion, and squamous cell carcinoma in the PP group significantly increased (p < .05). Persistent HPV infections are mainly caused by multiple types of HPV and high-risk HPV. Our region should particularly pay attention to the prevention and treatment of HPV 16, 52, and 58.

Laryngeal Papillomatosis Associated Dysplasia in the Adult Population

The objectives were to determine the prevalence of laryngeal dysplasia and associated human papilloma virus (HPV) subtypes in adult patients, 18 years or older, suffering from laryngeal papillomatosis at a tertiary care institution. Retrospective cohort study. Patients with biopsy proven laryngeal papillomatosis were identified via chart review. All available pathology specimens were reviewed by a dedicated head and neck pathologist to confirm/refute the diagnosis of laryngeal dysplasia, and grade the level of dysplasia. Interrater agreement was compared using cross-tabulation methods. Specimens identified to be positive for dysplasia underwent further testing via in situ hybridization for low-risk (6/11) or high-risk (16/18) HPV subtypes. Of the 85 subjects identified to have laryngeal papillomatosis, 24(28%) demonstrated laryngeal dysplasia. There was good interrater agreement on the presence of dysplasia; however, there was only fair agreement on the grade of dysplasia. Of the pathology specimens tested for HPV subtype, the majority of patients (62%) were positive for HPV 6/11, including all high-grade dysplasia patients. Three (12%) dysplasia specimens were negative for both high- and low-risk HPV subtypes. We found a 28% prevalence of dysplasia in our patient population with the majority of patients positive for low-risk HPV subtypes indicating that high-risk HPV subtypes do not predispose laryngeal papilloma patients to dysplasia.

Analysis of human papillomavirus infection and typing in Shanxi province

To investigate human papilloma virus (HPV) infection and typing in 7 640 cases of women in Shanxi province in order to provide theoretical basis for the prevention and treatment of the cervical cancer. Totally, 7 640 cases of cervical cell specimens in Shanxi provincial tumor hospital, screening and physical examination from 2012 January to 2013 May and 23 HPV genotypes were analyzed by PCR and reverse dot blot gene chip technology. A total of 1 441 cases of patients with HPV infection were to be found in 7 640 cases of women with an average age of (42.26 ± 19.15)years old. The total infection positive rate, infection rate of high-risk HPV, infection rate of low-risk HPV and infection rate of mixed high and low risk were 18.86% (1 441/7 640), 16.03% (1 225/7 640, including multiple high-risk of HPV infection), 4.88% (373/7 640, including multiple low-risk of HPV infection) and 2.05% (157/7 640) respectively. The rate of high-risk HPV infection was 85.01% (1 225/1 441) in total infection positive women. The most common subtype was HPV16 (34.70%, 523/1 507) and followed by HPV58 (11.48%, 173/1 507), HPV18 (7.43%, 112/1 507), HPV33 (7.10%, 107/1 507), HPV56 (6.04%, 91/1 507) and HPV52 (5.51%, 83/1 507) respectively in tested 18 high-risk HPV subtypes, and there was no HPV82. The most common subtype was HPV43 (38.13%, 151/396) and followed by HPV42 (22.22%, 88/396), HPV81 (20.45%, 81/396), HPV6 (11.87%, 47/396) and HPV11 (7.32%, 29/396) respectively in tested 5 low-risk HPV subtypes. The HPV infection positive rates were significantly different in different age groups and HPV total infection rate, high-risk infection rate in 41-50 year-old age group was the highest, 23.23%. The infection rates of single subtype of HPV and single high-risk subtype of HPV were 75.71% (1 091/1 441) and 61.35% (884/1 441) respectively in all cases of infection women and single high-risk subtype infection rate was 81.03% (884/1 091) in all cases of single subtype infection women. The infection rate of multiple subtype of HPV was 24.29% (350/1 441) in all cases with HPV infection. The double infections was most common (18.18%, 262/1 441) in which the women of double high-risk infections of HPV were 151 cases (10.48%, 151/1 441). The rates of double infection, triple infection and quadruple or more infection of HPV were 74.86% (262/350), 20.29% (71/350) and 4.89% (17/350) respectively in all cases with HPV multiple infection. The positive rates of HPV infection in different age groups were obvious difference. The positive rate of single infection of HPV was 17.80% (574/3 224) in cases of 41-50 years old group which higher than that in other groups(χ² = 20.18, P < 0.05). The more common high-risk HPV subtype is HPV16, HPV58, HPV18, HPV33, HPV56 and HPV52 and low-risk HPV subtype is HPV43, HPV42 in Shanxi province. HPV infection is most common in the age group of 41- 50 years old female.

Is real-time PCR the correct method to evaluate the incidence of human papillomavirus in prepuces of asymptomatic boys and men?

To investigate the prevalence of human papillomavirus (HPV) in prepuces of asymptomatic boys and men, the present study was designed. Two hundred and fifty male prepuce specimens who underwent circumcision due to phimosis were collected. Samples were subdivided into groups regarding their age: children (group I, 0-10 years), adolescents (group II, 11-20 years) and adults (group III, >20 years). HPV High Screen Real-TM Quant 2x kit detecting HPV 6 and 11 (low risk) as well as another kit for identification of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 (high risk) were used. Additionally, a Taq Man assay has been designed targeting the L1 gene of HPV 6, 11, 16 and 18. Evaluating the number of low-risk HPV subtypes, we found HPV 6 and 11 in 5.3 % of samples (n = 12/226). Concerning high-risk HPV, we found a positivity in 4 % of samples (n = 9/224). In contrast to low-risk data where no age distribution was observed, we found an age-specific accumulation of high-risk HPV subtypes in the children group (n = 6/9). A second independent assay (Taq Man PCR assay) measuring HPV 6, 11, 16 and 18 of all positive samples confirmed only the high-risk HPV subtypes of the Real-TM Quant 2x assay. Our study provides evidence that qPCR estimation for HPV infection obviously underestimates the incidence rate of infected prepuces in boys and men with phimosis. Contrary, an overestimation of the HPV infection rate with the in situ hybridization method of phimotic prepuces cannot be excluded.

Oral Multifocal Papillary Lesions in a Young Child: Clinico-Pathologic and Medico-Legal Considerations

Human papilloma virus (HPV) is a non-enveloped DNA virus that infects cutaneous and mucosal epithelial cells. Oral lesions of HPV can present as solitary or multifocal lesions, and multifocal lesions can represent a diagnostic challenge clinically with important medicolegal considerations in some cases. We report a unique case of a 12-year-old boy presenting with oral multifocal papillary mucosal lesions which upon biopsy was found to be consistent with a diagnosis of condyloma acuminatum or Heck’s disease histopathologically; in situ hybridization studies also confirmed positivity for low risk HPV subtypes in affected tissue. Based on the pathology results and our clinical protocols, we contacted social servicesto rule out the sexually transmitted disease condyloma. A final diagnosis of Heck’s disease was rendered after clinico-pathologic and social correlation. Cryotherapy with topical anesthesia was used to successfully treat the lesions with no evidence of recurrence on 6 month follow-up.

Expression of cyclin D1 and cyclin E significantly associates with human papillomavirus subtypes in Bowenoid papulosis

Human papillomavirus (HPV) incorporates high-risk HPV (hrHPV) and low-risk HPV (lrHPV) subtypes according to its contribution to oncogenesis. Different HPV subtypes could regulate the cell cycle of infected cells at different levels. To date, the expression of cyclin D1 and cyclin E in Bowenoid papulosis (BP) tissues and its association with HPV infection still remains elusive. In the present study, genotyping was performed to identify the HPV subtypes in 44 BP specimens. In addition, immunohistochemistry was performed to detect the expression of cell cycle related proteins cyclin D1 and cyclin E in BP tissues as well as normal tissues. We found that there were 20 patients with hrHPV subtypes, 6 patients with lrHPV subtypes, and 18 patients with combined high and low (hr/lr) HPV subtypes. Cyclin D1 expression in patients with hrHPV subtypes (P=0.0408), in patients with lrHPV subtypes (P=0.0002) and in patients with hr/lr HPV subtypes (P=0.0047) was significantly higher than that in normal controls, respectively. Cyclin D1 expression in patients with hr/lr HPV subtypes (P<0.0001) and in patients with lrHPV subtypes (P=0.0244) was significantly higher than that in patients with hrHPV subtypes, respectively. Cyclin E expression in patients with hrHPV subtypes (P<0.0001), in patients with lrHPV subtypes (P=0.0005), and in patients with hr/lr HPV subtypes (P<0.0001) was significantly higher than that in normal controls, respectively. Cyclin E expression in patients with hrHPV subtypes was significantly higher than that in patients with lrHPV subtypes (P=0.0032). Our data suggest that HPV infection is strongly associated with the pathogenesis of BP, and further support the notion that HPV may be involved in the regulation of the expression of cell cycle related proteins, cyclin D1 and cyclin E, in the pathogenesis of BP.

Prevalence and Seroprevalence of Low-Risk Human Papillomavirus in Korean Women

Little is known about the prevalence and seroprevalence of low-risk human papillomavirus (HPV) and the risk factors for HPV infection in Korean women. We determined the prevalence of low-risk HPV among 902 women aged 20-59 yr and the seroprevalence of low-risk HPV subtypes 6 and 11 among 1,094 women aged 9-59 yr in the general population. Genital low-risk HPV DNA was assessed by liquid hybridization and polymerase chain reaction. Antibody titers against HPV 6 and 11 were measured by a multiplexed competitive luminex technique. The prevalence of genital low-risk HPV was 4.9%. It reached its highest peak of 10.3% at 20-29 yr of age and a second peak of 3.2% at 50-59 yr of age. The seroprevalence of HPV 6 or 11 was 9.4%. It reached its highest peak of 12.7% at 25-29 yr of age and a second peak of 12.3% at 50-59 yr of age. In multivariable analysis, the number of lifetime sexual partners and past history of sexually transmitted diseases were associated with the seroprevalence but not prevalence of HPV. It is suggested that younger women should receive prophylactic HPV vaccination before they become sexually active and exposed to HPV in their 20s. This study provides baseline data for developing HPV vaccination programs and monitoring vaccine efficacy in Korea.

Prophylaktische und therapeutische Vakzinen gegen humane Papillomviren

Infection with human papilloma virus (HPV) has been identified as the cause of recurrent papillomatosis and of a subgroup of squamous cell carcinomas of the head and neck. A change in prevalence of these lesions, especially for oropharyngeal carcinoma, can be expected as a consequence of the introduction of prophylactic HPV vaccines for young women, targeting the most frequent high- and low-risk HPV subtypes. Vaccination for the major low-risk HPV types has proven to be highly effective against genital warts and activity against papillomatosis can be expected. The possibilities of prophylactic HPV vaccination as well as new developments and the rationale for therapeutic vaccines are discussed on the basis of the current literature.

Relationship between nasal inverted papilloma and human papillomavirus subtypes

To study the distribution of human papillomavirus (HPV) subtypes in nasal inverted papilloma (NIP), and to evaluate the relationship between HPV and NIP. Twenty-one HPV subtypes were detected in paraffin-embedded tissues of 101 cases of NIP by flow through hybridization and gene chip (HybriMax), 24 cases of normal nasal mucosa were used as controls. HPV positive rates of NIP were 64.36% (65/101). Benign NIP group, NIP with atypical hyperplasia group, NIP with cancerous group of HPV positive rates were 59.7% (46/77), 81.8% (18/22) and 50% (1/2) respectively. The control group was negative (0/24). The comparison between NIP group and control group was statistically significant (chi(2) = 32.178, P < 0.05). Benign NIP group and NIP with atypical hyperplasia group were compared, but no statistically significance (chi(2) = 3.649, P = 0.056) was found. The constituent ratio of benign NIP group and NIP with atypical hyperplasia group in high, low-risk HPV subtypes infections was compared, a statistically significance (chi(2) = 10.412, P < 0.05) was found. The occurrence of NIP was related with HPV infection. High-risk HPV subtype infections or multiple infections will prompt benign NIP to NIP with atypical hyperplasia. Understanding the distribution of HPV subtypes in the NIP is helpful to predict the clinical behavior.

Papillomas of the External Ear Canal: Report of Ten cases in Chinese Patients with HPV In Situ Hybridization

Squamous papilloma is a benign exophytic proliferation which can occur occasionally in the external ear canal. It is widely assumed that the Human Papilloma Virus (HPV) is an etiologic factor of papillomas. Available techniques for detection of HPV genomes include immunohistochemistry, Southern blot hybridization, in situ hybridization (ISH), and polymerase chain reaction. To our knowledge, HPV typing has not been reported on tissue sections of papillomas in the external ear canal. We report HPV ISH analysis in ten cases of papillomas, involving the external ear canal in Chinese patients. These papilloma excrescences were less than 1 cm in diameter, and were benign morphologically. Automated HPV ISH analysis was performed for the hybridization of DNA probes, including both low-risk and high-risk HPV subtypes. HPV ISH results revealed that seven out of ten cases were positive for low-risk HPV (6, 11), three cases demonstrated no hybridization for low-risk HPV probe, and none of the cases revealed any detection of high-risk HPV (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, and 66). On follow-up after 18-29 months (average 24.5 months), eight patients were doing well, with no local recurrence after excision. Two patients were lost to follow-up. Our results confirm that benign papillomas of the external ear canal are associated with low-risk HPV infection with benign behavior and neither recurrence nor high grade dysplasia.

BD ProEx™C immunostaining in extramammary Paget's disease and perineal melanoma

The differential diagnosis of perineal biopsies can include squamous intraepithelial lesions, extramammary Paget's disease, and melanoma. Less frequently two of these lesions coexist. BD ProEx™C is a recently developed immunoassay that targets expression of two genes shown to be associated with cervical cancer. Immunostaining for ProEx™C has been validated in cervical cytology and positive staining has also been shown to be strongly associated with human papilloma virus (HPV)-induced cervical and anal intraepithelial neoplasia in biopsies. We observed positive staining for ProEx™C in Paget cells in all of 26 cases of Paget's disease irrespective of tissue site (extramammary, mammary) and in melanoma cells in all of 12 cases of primary perineal melanoma with immunostaining in >50% of malignant cells in 73% of Paget disease cases and 43% of perineal melanoma cases. Positive staining was heterogeneous and exclusively nuclear in all cases. In situ hybridization was negative for low-risk and high-risk HPV subtypes in all Paget and melanoma cases that were tested. Currently neither of these lesions is known to be HPV related although according to the literature the possibility of a role for HPV in melanoma is still unsettled. Relevant literature is reviewed.

Detection of Human Papillomavirus Infection of the Cervix in Very Elderly Women Using PCR

To determine the incidence of human papillomavirus (HPV) infection and the morphologic lesions induced by HPV infection of the uterine cervix in elderly Japanese women (including very elderly women) and to clarify the natural history and outcome of HPV infection. We detected squamous intraepithelial lesions (SIL) by cytology and the presence of HPV infection by PCR on cervical smears obtained at autopsy from 335 women ages 60 to 105 years (mean, 82.7 years). Two primers were used for PCR, one for low-risk HPV subtypes and one for high-risk HPV subtypes. SILs were observed in 20 (6.0%) of the women autopsied; 18 (5.4%) had low-grade SIL and 2 (0.6%) had high-grade SIL. HPV-DNA was not detected in any of the women with normal cervical cytology but was found in 9 (45.0%) of the 20 with SIL (2.7% of all subjects). Of these 9 women, 2 (22%) were positive for low-risk types of HPV and 7 (78%) were positive for high-risk types. All 9 had spent their last days in hospitals or nursing homes, the duration of institutional care ranging from 17 days to 10 years 2 months. Our results suggest that HPV infection of the cervix may occasionally persist for long periods of time (the maximum duration noted in this study being 10 years 2 months). It is also possible that HPV infection in young women with normal cervical cytology will not persist into advanced age.