Human papillomavirus segregation patterns in genital and nongenital warts in prepubertal children and adults.

This study compared the segregation patterns of human papillomavirus (HPV) in genital and nongenital warts in prepubertal children and adults. HPV 2 was detected in most nongenital warts in children and adults, whereas neither HPV 6 or 11 was detected at nongenital sites in either group with the use of in situ or Southern blot hybridization analyses. Of nine genital tract lesions in children. HPV 2 was detected in two and HPV 6 or 11 in six. More than 90% of cases of regional tract condylomata in adults contained HPV 6 or 11. HPV 2 was not detected in any of 99 genital tract lesions in adults. It is concluded that HPV 6/11 cannot proliferate at nongenital cutaneous sites and HPV 2 can proliferate in the genital tract of children but not adults. Thus, the detection of HPV 6 or 11 in a genital wart in a child implies, assuming cutaneous transmission, infection from a genital site, whereas the detection of HPV 2 presumes nongenital transmission.     

Detection of Multiple Human Papillomavirus Types in Condylomata Acuminata Lesions from Otherwise Healthy and Immunosuppressed Patients

Condylomata acuminata, or genital warts, are proliferative lesions of genital epithelium caused by human papillomavirus (HPV) infection. HPV types 6 and 11 are most often detected in these lesions. Genital lesions consistent with exophytic condylomata acuminata were removed by excision biopsy from 65 patients, 41 of whom were otherwise healthy individuals (control group) and 24 of whom had conditions known to cause immunosuppression. Histologically, the majority of the lesions were typical condylomata acuminata. Three lesions removed from immunosuppressed individuals also contained foci of moderate to severe dysplasia (intraepithelial neoplasia grade II/III). A recently developed PCR and reverse blot strip assay was used to determine the specific HPV types present in the genital lesions. With a set of oligonucleotide primers based on the same primer binding regions used for the MY09 and MY11 primer pair, this PCR assay detects the presence of 27 HPV types known to infect the genital tract. All but two condylomata acuminata contained either HPV type 6 or 11. The predominant type in the lesions from control patients was HPV 6, while lesions from immunosuppressed types most often contained HPV 11. Condylomata acuminata from immunosuppressed patients contained significantly more overall HPV types than lesions from the control group. HPV types associated with an increased risk of dysplasia (high-risk types) were detected in 42 (64.6%) of the total of 65 specimens; 18 (43.9%) specimens were detected in the 41 otherwise healthy individuals, and 24 (100%) specimens were detected in the 24 immunosuppressed patients. HPV 16 was the most common high-risk type detected, found in 21 of 65 (32.3%) specimens. After HPV types 6 and 11, HPV types 53 and 54 were the most frequently detected low-risk HPV types. This study demonstrates that a high percentage of condylomata acuminata lesions contain multiple HPV types, including types associated with a high risk of dysplastic abnormalities. Further studies are needed to determine the influence these additional HPV types have on the epidemiology of genital tract HPV infections and the natural history of condylomata acuminata, especially in immunosuppressed patients.     

Detection of Human Papillomavirus Types 6 and 11 in Pubic and Perianal Hair from Patients with Genital Warts

Genital human papillomavirus (HPV) types 6 and 11 are of clinical importance due to their role in the development of anogenital warts. A pilot study was performed to investigate whether DNAs from HPV types 6 and 11 are present in hairs plucked from the pubic and perianal regions and eyebrows of patients with genital warts at present and patients with a recent history of genital warts. Genital HPV DNA was detected in 9 of 25 (36%) pubic hair samples and in 11 of 22 (50%) perianal hair samples by the CPI/CPIIg PCR. After sequencing of 17 of 20 samples, HPV type 6 or 11 was detected in 6 of 25 (24%) hair samples from the pubis and 8 of 22 (36%) hair samples from the perianal region. These types were not detected in plucked eyebrow hairs. In contrast, the HPV types associated with epidermodysplasia verruciformis were detected in similar proportions (62%) in both samples of pubic and eyebrow hairs. Moreover, HPV type 6 and 11 DNAs were detected in pubic hairs plucked from two patients who had been successfully treated and who did not show any lesion at the time of hair collection; this finding is an argument that HPV DNA may persist in this region. The presence of genital HPV types in plucked pubic and perianal hair suggests that there is an endogenous reservoir for HPV which may play a role in the recurrences of genital warts.     

High-grade dysplasia in genital warts from two patients infected with the human immunodeficiency virus

Cancer-associated human papillomavirus (HPV) types are detected in genital warts removed from immunosuppressed individuals more commonly than from those occurring in otherwise healthy individuals. The prognosis of genital warts containing cancer-associated HPV types is not known. Because it is assumed that genital warts are benign lesions, they are usually treated by destructive therapies without prior knowledge of histopathology. The aim of the present study was to determine whether genital warts from individuals with or without human immunodeficiency virus (HIV) contain high-risk HPV types or areas of dysplasia. The study design was a nonrandomized analysis of genital warts removed by excision biopsy from 15 HIV-infected patients and 15 HIV-negative patients. The tissue was analyzed for HPV DNA by hybrid capture, and microscopic sections of each biopsy were examined for areas of dysplasia. Genital warts from HIV-infected patients contained cancer-associated (“high risk”) HPV types in 9 of 15 cases, including 1 that contained only a high-risk type. High-grade dysplastic abnormalities were present in 2 of the 15 lesions from this group, both of which contained high-risk HPV types. Four genital warts removed from HIV-negative patients contained high-risk HPV types, but none contained dysplastic abnormalities. It is concluded that genital warts from HIV-infected patients often contain high-risk HPV types. Such lesions may exhibit dysplastic changes. The frequency of dysplastic changes in genital warts from HIV-infected patients is not known. Biopsy of genital warts may be indicated prior to additional therapy in HIV-infected patients, and surgical removal should be considered as a preferred treatment option in these patients. J. Med. Virol. 54:69–73, 1998. © 1998 Wiley-Liss,Inc.     

Use of PGMY primers in L1 consensus PCR improves detection of human papillomavirus DNA in genital samples

The novel PGMY L1 consensus primer pair is more sensitive than the MY09 and MY11 primer mix for detection and typing with PCR of human papillomavirus (HPV) DNA in genital specimens. We assessed the diagnostic yield of PGMY primers for the detection and typing of HPV by comparing the results obtained with PGMY09/PGMY11 and MY09/MY11/HMB01 on 299 genital samples. Amplicons generated with PGMY primers were typed with the line blot assay (PGMY-line blot), while HPV amplicons obtained with the degenerate primer pool MY09/MY11/HMB01 were detected with type-specific radiolabeled probes in a dot blot assay (standard consensus PCR test). Cervicovaginal lavage samples (N = 272) and cervical scrape samples (N = 27) were tested in parallel with both PCR tests. The PGMY-line blot test detected the presence of HPV DNA more frequently than the standard consensus PCR assay. The concordance for HPV typing between the two assays was 84.3% (214 of 255 samples), for a good kappa value of 0.69. Of the 177 samples containing HPV DNA by at least one method, 40 samples contained at least one HPV type detected only with PGMY-line blot, whereas positivity exclusively with the standard consensus PCR test was found for only 7 samples (P < 0.001). HPV types 45 and 52 were especially more frequently detected with PGMY than MY primers. However, most HPV types were better amplified with PGMY primers, including HPV-16. Samples with discordant results between the two PCR assays more frequently contained multiple HPV types. Studies using PGMY instead of MY primers have the potential to report higher detection rates of HPV infection not only for newer HPV types but also for well-known genital types.     

Human papillomavirus (HPV) type distribution and serological response to HPV type 6 virus-like particles in patients with genital warts.

Thirty-nine patients with condylomas (12 women and 27 men) attending a dermatology clinic were tested for genital human papillomavirus (HPV) DNA and for seroprevalence to HPV type 6 (HPV6) L1 virus-like particles. The L1 consensus PCR system (with primers MY09 and MY11) was used to determine the presence and types of HPV in sample specimens. All 37 (100%) patients with sufficient DNA specimens were positive for HPV DNA, and 35 (94%) had HPV6 DNA detected at the wart site. Three patients (8%) had HPV11 detected at the wart site, and one patient had both HPV6 and -11 detected at the wart site. Thirteen additional HPV types were detected among the patients; the most frequent were HPV54 (8%) and HPV58 (8%). Baculovirus-expressed HPV6 L1 virus-like particles were used in enzyme-linked immunosorbent assays to determine seroprevalence among the patients with warts. Seronegativity was defined by a control group of 21 women who were consistently PCR negative for HPV DNA. Seroprevalence was also determined for reference groups that included cytologically normal women who had detectable DNA from either HPV6 or HPV16 and women with HPV16-associated cervical intraepithelial neoplasia. Among the asymptomatic women with HPV6, only 2 of 9 (22%) were seropositive, compared with 12 of 12 (100%) female patients with warts. A similar trend in increased HPV6 seropositivity with increased grade of disease was found with the HPV16 DNA-positive women, whose seroprevalence increased from 1 in 11 (9%) in cytologically normal women to 6 in 15 (40%) among women with cervical intraepithelial neoplasia 1 or 3. However, only 4 of 25 (16%) male patients were seropositive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Overexpression of the proto-oncogene C-jun in association with low-risk type specific human papillomavirus infection in condyloma acuminata

Infection with different types of human papillomavirus (HPV) is associated with neoplasia at different anatomic sites. The “low-risk” HPVs (LR-HPV) are responsible for benign genital lesions such as condyloma acuminata. In order to clarify the tumorigenic mechanism of LR-HPV, the HPV infection status was investigated and the expression of the c-jun proto-oncogene in different HPV-related skin and genital lesions analyzed. Of the 17 condyloma specimens analyzed by Western blotting, 13 cases (76.5%) exhibited overexpression of the c-jun gene. All 13 cases harbored high copy numbers of the LR-HPV genome with an average of 926 copies per cell, whereas the other four cases had an average of 12 copies of LR-HPV per cell (P < 0.001). Further typing of HPV by Southern blotting revealed that HPV-6 and HPV-11 infections predominated in c-jun positive cases. The c-jun protein was detected much less frequently in cervical cancers (three of 29, or 10.3%) and skin warts (one of 10), and was not detected in five genital polyps or in five normal cervical tissues. These findings suggest a type 6/11-specific induction of c-jun gene expression in HPV-related neoplastic lesions. © 1996 Wiley-Liss, Inc.     

Characterization of human papilloma virus types in condylomata acuminata in children by in situ hybridization

The presence of human papilloma virus (HPV) DNA sequences of types 6, 11, 16, and 18 was determined by in situ hybridization under stringent conditions on archival paraffin-embedded tissue sections in eight condylomata acuminata observed in children below the age of 12 years. Viral sequences were detected in seven of eight cases: all of them contained HPV 6, four contained also HPV 11, and one contained HPV 16 and 18. Papilloma virus common antigen was detected in only three of eight cases, all of them being positive also by in situ hybridization. We conclude that most condylomata acuminata in children are associated with the same types found in anogenital lesions in adults. Since little is known about the long-term significance of genital condylomas in children the identification of the papilloma virus type may prove to be important as a prognostic tool particularly in patients infected with HPV types 16 and 18, thought to have high oncogenic potential.     

Spotlight on Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine (Gardasil®) in the Prevention of Premalignant Genital Lesions, Genital Cancer, and Genital Warts in Women

Quadrivalent human papilloma virus (HPV) [types 6, 11, 16, 18] recombinant vaccine (Gardasil®; Silgard®) is composed of virus-like particles (VLPs) formed by self-assembly of recombinant L1 capsid protein from each of HPV types 6, 11, 16, and 18. The VLPs are noninfectious, containing no DNA, and are highly immunogenic, inducing high levels of neutralizing antibodies against the particular HPV types when administered to animals or humans. Quadrivalent HPV vaccine is indicated for use from the age of 9 years for the prevention of premalignant genital lesions (cervical, vulvar, and vaginal), cervical cancer, and external genital warts (condyloma acuminata) causally related to certain oncogenic or specific HPV types. In placebo-controlled clinical trials, quadrivalent HPV vaccine administered as three doses over 6 months provided high-level protection against infection or disease caused by the vaccine HPV types over 2–4 years of follow-up in females aged 15–45 years who were naive to the vaccine HPV types. A degree of cross-protection against certain other non-vaccine high-risk HPV types was also observed. The vaccine is not effective against current infection with a vaccine HPV type. Girls or women with current infection with one or more of the vaccine HPV types gained protection from infection or disease caused by the remaining vaccine HPV types and they were also protected against reinfection with the same HPV type after clearance of an infection caused by a vaccine HPV type. High seroconversion rates and high levels of anti-HPV antibodies were observed in all vaccinated individuals of all age ranges from 9 to 45 years. No correlation was found between antibody levels and protective efficacy of the vaccine. Rechallenge with quadrivalent HPV vaccine produced a potent anamnestic humoral immune response. The vaccine is generally well tolerated and is projected to be cost effective in most pharmacoeconomic models. Therefore, quadrivalent HPV vaccine offers an effective means, in combination with screening programs, to substantially reduce the burden of HPV-related precancerous lesions and cancer, particularly cervical cancer, as well as anogenital warts.     

生殖器疣活检标本中HPV多重检测技术的建立

目的探索生殖器疣活检标本中人乳头瘤病毒（HPV）的多重检测分型技术,为我国生殖器疣感染HPV的检测和分型研究的开展提供有效手段。方法针对病毒L1区基因序列自行设计通用引物MY09、MY11、GP5＋和GP6＋,并对反应条件进行优化,建立基于聚合酶链式反应（PCR）及序列分析的检测生殖器疣活检标本中HPV感染型别的方法。结果采用巢氏PCR方法能够特异扩出140bp的目的条带,实现HPV感染的定性检测;通过对目的基因片段的测序分析能够实现单型别感染/多型别复合感染HPV的分型和鉴定,并可以检测到HPV少见的特殊类型,同时也能提供已知的HPV型别的突变信息。结论基于HPV病毒L1区基因序列建立的PCR和序列分析检测技术是快速检测和分型生殖器疣活检标本中HPV的一种有效方法。     

The seroprevalence of IgG antibodies to human papillomavirus (HPV) types HPV-16, HPV-18, and HPV-11 capsid-antigens in mothers and their children

Human papillomavirus (HPV) types causing anogenital lesions and cancer are accepted as being sexually transmitted. The methods whereby children acquire these anogenital type HPV infections are unclear. The present study determined the prevalence of anti-HPV-16, HPV-11 and HPV-18 IgG antibodies in mothers and their children in an attempt to identify evidence of HPV transmission from mother to child. HPV virus-like particles (VLP) VLP-16, VLP-11 and VLP-18 were used in enzyme-linked immunosorbent assay to identify IgG antibodies in serum from 100 mothers and their 111 children. Antibodies to VLP-16, VLP-11 and VLP-18 were found in serum from 17%, 21% and 16% of mothers, respectively and seroprevalences were 9%, 11.7% and 9.9%, respectively amongst the children. Of the 111 children, 23 (20.7%) showed antibodies to one or more of the three HPV types tested. Seven of these (30.4%) HPV IgG positive children had the same antibodies to one or more HPV types as their mothers. The prevalence of HPV-11 was similar in children of seropositive compared with seronegative mothers (14% and 11%, respectively). The prevalence of HPV-16 and HPV-18 was higher in children of seropositive mothers compared with seronegative mothers (for HPV-16, 18% and 7%, respectively, P = 0.1, for HPV-18, 19% and 8%, respectively, P = 0.2). None of these differences were statistically significant indicating a lack of correlation between antibodies in mothers and children and no evidence to support vertical or horizontal mother to child transmission of HPV infection. Indications were of multiple sources of HPV infection in the children.     

Analysis of human papillomavirus types in exophytic condylomata acuminata by hybrid capture and Southern blot techniques.

Exophytic condylomata acuminata of the external genitalia of 40 patients were analyzed for human papillomavirus (HPV) DNA by the Southern blot and hybrid capture methods. All lesions were initially analyzed by the Southern blot method by using a mixture of HPV type 6, 11, 16, and 18 whole genomic probes. Southern blots demonstrated characteristic PstI restriction patterns of HPV type 6, 11, or 16 in all but one lesion. HPV 6 subtypes accounted for 28 of 39 HPV-positive lesions. Twenty-seven of these 28 lesions contained HPV type 6a, and 1 lesion contained HPV type 6c. Eight lesions contained HPV type 11 and three contained HPV type 16. Two of the three condylomata acuminata containing HPV type 16 were obtained from solid-organ transplant recipients receiving immunosuppressive medications. The third lesion containing HPV type 16 was a typical exophytic condyloma acuminatum from a woman with previously resected vulvar carcinoma. The hybrid capture assay detected HPV DNAs in all lesions except the Southern blot-negative lesion. Twenty-five lesions were positive for the A probe only (HPV types 6 and 11 and related types). All of these lesions were found to contain HPV type 6 or 11 sequences in the Southern blot assay. The remaining 14 lesions were positive for both the A probe and the B probe (HPV types 16 and 18 and related types). The strongest signal in these 14 lesions by the hybrid capture assay was consistent with the result of the Southern blot assay in all but one case. We conclude that (i) HPV type 6a is the most common type found in these lesions, (ii) HPV type 16 may be present more often in exophytic condylomata acuminata from immunosuppressed individuals, (iii) hybrid capture is a useful tool for documenting the presence of HPV sequences in DNAs from exophytic condylomata acuminata, and (iv) in samples containing multiple HPV types, hybrid capture allows detection of minority HPV types.     

Men’s beliefs about HPV-related disease

While human papillomavirus (HPV) infection is associated with genital warts, anal cancer, and oral cancer, limited research has examined what men think causes these diseases. We sought to examine knowledge and beliefs about HPV-related disease among gay and bisexual men, who are at high risk for HPV infection and HPV-related cancers, and compare them to heterosexual men. We conducted an online survey in January 2009 with a national sample of men aged 18–59 who self-identified as either gay or bisexual (n = 312) or heterosexual (n = 296). The response rate was 70%. Fewer than half of men knew that HPV can cause genital warts (41%), anal cancer (24%), and oral cancers (23%). However, gay and bisexual men typically knew more than heterosexual men about these topics. Overall, most men believed that sexual behavior causes genital warts (70%) and anal cancer (54%), and tobacco use causes oral cancer (89%). Perceived causal factors differed substantially among the three diseases, while differences by sexual orientation were fewer and smaller in magnitude. Many men were unaware that HPV infection can cause genital warts, oral cancer, and anal cancer.     

Could human papillomaviruses be spread through blood?

The human papillomaviruses (HPVs) are epitheliotropic viruses that require the environment of a differentiating squamous epithelium for their life cycle. HPV infection through abrasion of the skin or sexual intercourse causes benign warts and sometimes cancer. HPV DNA detected in the blood has been interpreted as having originated from metastasized cancer cells. The present study examined HPV DNA in banked, frozen peripheral blood mononuclear cells (PBMCs) from 57 U.S. human immunodeficiency virus (HIV)-infected pediatric patients collected between 1987 and 1996 and in fresh PBMCs from 19 healthy blood donors collected in 2002 to 2003. Eight patients and three blood donors were positive mostly for two subgroups of the HPV type 16 genome. The HPV genome detected in all 11 PBMC samples existed as an episomal form, albeit at a low DNA copy number. Among the eight patients, seven acquired HIV from transfusion (three associated with hemophilia) and one acquired HIV through vertical transmission; this patient also had received a transfusion before sampling. Our data suggest that PBMCs may be HPV carriers and might spread the virus through blood.     

Human papillomavirus genomes in male urethral cells.

Sixty-four samples of urethral cells from male sexual partners of women with genital human papillomavirus (HPV) infection were analyzed for the presence of HPV types 6, 11, 16, and 18 by polymerase chain reaction (PCR) followed by slot blot hybridization. Additional samples from 37 of these subjects were analyzed for the presence of viral cytopathic effects by conventional cytology. By PCR, HPV DNA was detected in 21% (14/64) of samples. By cytology, 16% (6/37) of the samples showed cellular changes consistent with HPV infection. Polymerase chain reaction and cytology results were concordant for presence and absence of HPV in 5 and 28 cases, respectively. Three additional HPV-positive cases were obtained with PCR in the cytologically negative samples. The cytologic abnormalities were found to be associated with the presence of both low-risk HPV types and meatal acetoreactivity. On the contrary, HPV DNA positivity by PCR was unrelated to viral type and peniscopic findings. Urethral HPV infection was detected by PCR in 30% of males with visible penile lesions and in 18% of those without. These results indicate that PCR analysis of urethral samples is a helpful adjunct to cytology for the detection of HPV DNA in absence of cytologic evidence of infection.     

Influence of fixation on human papillomavirus DNA detection in frozen and embedded paraffin lesions by in situ hybridization with biotinylated probes.

Series of frozen or paraffin-embedded tissues from various body sites, taken from non-immunosuppressed or immunosuppressed patients with persistent papilloma lesions were examined for the presence of group specific antigen from human papillomavirus (HPV) by indirect immunofluorescence or HPV DNA by in situ hybridization with biotinylated probes. We have shown that it is possible to detect HPV DNA after fixation of tissues in neutral formalin, Bouin's or Baker's solution. However, the sensitivity was reduced as compared to frozen tissues. The HPV DNA was detected in nuclei of heavily infected epithelial cells such as plantar or hand warts or in dispersed cells containing high copy numbers of HPV DNA from lesions such as squamous cell carcinomas or keratoacanthomas. In premalignant or malignant lesions of both immunosuppressed or non-immunosuppressed patients, HPV DNA was rarely detected after fixation. HPV types commonly described for skin and genital samples were identified in non-immunosuppressed patients, whereas in transplant recipients oncogenic HPV type 16 was identified in benign warts as well as in premalignant or malignant lesions. Positive reactions with several HPV types were more frequent in lesions from grafted patients than from the normal population. Virus antigen was detectable more frequently in frozen sections than in fixed tissues. Our findings indicate that in situ hybridization is an appropriate and rapid technique to study the presence of HPV infection. However, numerous controls are needed to avoid misinterpretations.     

Detection of multiple types of human papillomavirus in a giant condyloma from a grafted patient. Analysis by immunohistochemistry, in situ hybridisation, Southern blot and polymerase chain reaction.

Immunosuppressed patients such as transplant recipients are known to develop multiple lesions suggestive of human papillomavirus (HPV) infection. A giant anal condyloma was obtained from a transplant patient; several fragments taken from different areas were examined for the presence of HPV DNA using in situ hybridisation, polymerase chain reaction (PCR) and Southern blot. Typical koilocytes were seen in routinely stained tissue sections, suggesting an HPV infection; furthermore, group specific HPV antigen was detected in one of four frozen fragments. Different results were obtained by in situ hybridisation according to the fragment tested. HPV types 6/11 were detected in each of the five fragments, frozen or fixed in Bouin's or formalin solutions. However, the number of HPV DNA positive cells and the intensity of the reaction greatly varied with the specimen. HPV 16 and 18 probes also reacted positively with the sample fixed in formalin; a stronger signal was observed with HPV 18 in one large focus than with HPV 16. HPV type 5 was detected in a few isolated cells of two frozen fragments. With the Southern blot technique, the profile of an HPV 6/11 was seen only in one of two frozen fragments; in this case, the bands were intense. A slight positive reaction was also obtained in one frozen fragment with HPV 16 probe. Four frozen fragments were analyzed with PCR: HPV 6/11 was detected in each fragment; HPV 18 was detected in the four samples but with different intensities; HPV types 5 and 16 did not show any positive signal. In conclusion, the lesion is an example of infection with several HPV types, demonstrated by three different techniques. This suggests the need for careful dermatological or colposcopic follow-up of transplant recipients, in order to prevent possible malignant transformation of anogenital lesions.     

Distribution of human papillomavirus types in the anogenital tract of females and males

Human papillomavirus (HPV) infection is the most common sexually transmitted infection in both men and women, but there are limited data comparing the prevalence of HPV infection between genders and in different anogenital sites. This cross‐sectional analysis describes the distribution of HPV types in the genital tract of 3,410 consecutive females and 1,033 males undergoing voluntary screening for HPV and referred to a single institution. The relationship between specific HPV types and the presence of anogenital lesions was examined. In both females and males, the overall prevalence of HPV infection was about 40%. A wide variety of HPV types was identified, but the prevalence of different types was remarkably similar in the two genders, even when considering different anatomical sites. HPV‐6 was the most frequent (prevalence 13%) type in all anogenital sites in men followed by HPV‐16 (7%), while HPV‐16 was the most common type in women (about 6%), either in the cervix, vagina, or vulva, followed by HPV‐6. In addition to HPV‐16, HPV‐58, HPV‐33, HPV‐31, and HPV‐56 were the carcinogenic types detected most commonly and were significantly associated with high‐grade squamous intraepithelial cervical lesions, while HPV‐53 and HPV‐66 were the most common among possibly carcinogenic types. In both genders, anogenital warts were associated with HPV‐6 and HPV‐11 infection, and, less frequently, with other types, like HPV‐54, HPV‐62, and HPV‐66. These results show that genital HPV infection involves numerous HPV types, which have similar distribution patterns in females and males and in different anogenital anatomical sites. J. Med. Virol. 82:1424–1430, 2010. © 2010 Wiley‐Liss, Inc.     

Tumor-specific and gender-specific pre-vaccination distribution of human papillomavirus types 6 and 11 in anogenital warts and laryngeal papillomas: a study on 574 tissue specimens

Anogenital warts and laryngeal papillomas are two most important benign tumors etiologically linked with HPV. In the study, which included both the largest number of laryngeal papilloma tissue specimens (152 specimens from 152 patients) to date and the largest number of prospectively collected and histologically confirmed tissue specimens of anogenital warts obtained from both genders (422 specimens from 315 patients), HPV DNA was detected in 413/422 (97.9%) of anogenital warts and 139/152 (91.4%) of laryngeal papillomas. HPV‐6 and/or HPV‐11 were detected in 291/315 (92.4%) patients with anogenital warts and in 138/152 (90.8%) patients with laryngeal papillomas, indicating that the great majority of both tumors could be prevented with prophylactic quadrivalent vaccine. The HPV‐6 gender‐specific distribution in both anogenital warts and laryngeal papillomas was not statistically significant. In contrast, HPV‐11 was found almost three times more often in males than in females with anogenital warts (16.5% vs. 6.3%; P = 0.008), with a gender neutral HPV‐11 type distribution in laryngeal papillomas. The overall HPV DNA prevalence in anogenital warts was significantly different from that in laryngeal papillomas (97.1% vs. 91.4%; P = 0.01). In the first comparison of the HPV‐6/HPV‐11 type‐specific distribution between patients suffering from anogenital warts and laryngeal papillomas with the same geographic and ethnic background, a significant imbalance in tumor‐specific distribution of HPV‐6 and HPV‐11 was identified: HPV‐6 was statistically more often present in anogenital warts than in laryngeal papillomas (79.0% vs. 59.2%; P = 0.000013), whereas HPV‐11 was statistically more frequent in laryngeal papillomas than in anogenital warts (28.9% vs. 12.4%; P = 0.00003). J. Med. Virol. 84: 1233–1241, 2012. © 2012 Wiley Periodicals, Inc.     

The use of nested polymerase chain reaction and restriction fragment length polymorphism for the detection and typing of mucosal human papillomaviruses in samples containing low copy numbers of viral DNA

Mucosal human papillomaviruses (HPVs) that infect the genital area have also been shown to infect the oral cavity. In this study a restriction fragment length polymorphism (RFLP) method was developed on a nested polymerase chain reaction (PCR) product to identify ten high risk HPV types 16, 18, 31, 33, 35, 45, 51, 52, 58 and 59 as well as the low risk HPV 11. HPV DNA was detected in 23/31 (74%) of buccal specimens using a sensitive nested PCR employing degenerate consensus primers (Williamson and Rybicki, 1991). Consensus PCR using the PGMy09/11 primers. was able to detect HPV in only 29% of the specimens that had tested positive using the nested HPV PCR primers. HPV 11 type specific primers detected HPV 11 DNA in only 66% of the specimens showing HPV 11 DNA by means of nested PCR and RFLP. A Genbank search revealed that the PCR primers could detect a wide range of mucosal HPV types including types HPV 70, 72 and 73 which have all been isolated from immunocompromised patients. Of the 23 buccal specimens that were positive for HPV DNA, 13 were single infections, five were dual infections and three were triple infections. The HPV types identified by RFLP were: HPV 11 (18/23), HPV 18 (8/23), HPV 16 (3/23), and HPV 33 (1/23). HPV 13 (2/23) was identified by direct sequencing of the inner amplicon of the PCR product.