HPV6／11、HPV16／18与HPVL1蛋白检测在男性阴茎乳头状增生陛病变诊断中的应用

目的：调查男性阴茎乳头状增生性病变患者的HPV6／11、HPV16／18和HPVL1蛋白表达情况,确定病理诊断应用依据。方法回顾性调查130例男性阴茎乳头状增生性病变患者,采用常规病理组织学方法、免疫组化和原位杂交技术检测男性阴茎乳头状增生性病变患者手术标本的HPV6／11、HPV16／18和HPVL1蛋白表达情况。结果130例阴茎上皮乳头状增生性病变病例,尖锐湿疣、低级别上皮内病变、高级别上皮内病变和鳞癌分别占64．6％、16．9％、10．8％、7．7％。尖锐湿疣中HPV6／11、HPVL1蛋白表达阳性率为92．9％和97．6％,高于其他三组病变。低级别上皮内病变HPV16／18表达阳性率为81．8％,高于其他3组病变。结论对于HPVL1表达阴性的男性阴茎上皮乳头状增生性病变患者应该严格随访。     

In situ hybridization study of human papillomavirus from the penile cancer

The histochemical detection of human papillomavirus (HPV) was performed using the technique of in situ hybridization from the formalin fixed paraffin embedded specimens of penile carcinoma and condylomata+ acuminata . One of 19 penile cancer cases (5.3%) revealed the positive staining on the nuclei of the tumors for HPV type 16/18. However, the positive nuclei were scattered and localized in small part of the tumor which showed no koilocytosis. On the contrary, 11 of 12 condyloma acuminata cases (91.7%) showed positive staining on the nuclei of the tumors for HPV type 6/11, also 5 of the 11 cases (45.5%) revealed cross reaction for other type of HPV. The HPV types 6/11, 16/18 and 31/33/35 may be unrelated to the pathogenesis of the Japanese penile carcinoma. However, further study is necessary to evaluate that the number of HPV-DNA copy in our cases is too small, or the other type of HPV is responsibility.     

Aggressive giant condyloma acuminatum associated with oncogenic human papilloma virus: a case report

Malignant transformation has been described in 30% of cases of giant anorectal condyloma acuminatum. The authors report on a 33-year-old man who was heterosexual and HIV negative and who had a giant anal condyloma. Despite aggressive therapy with multiple fulgurations, interferon alpha and isotretinoin, an invasive squamous cell carcinoma of the rectum developed. An abdominoperineal resection was done followed by radiotherapy and chemotherapy, but this treatment regimen was unsuccessful in controlling the progression of his carcinoma. Human papillomavirus (HPV) serotyping in tumoral tissue was positive for HPV types 11 and 16. In patients with giant anorectal condylomas associated with oncogenic HPV, the course of the disease may be aggressive, so they may benefit from early surgical and medical intervention.     

Human papillomavirus-associated early vulvar neoplasia investigated by in situ hybridization

Of 21 consecutive cases of early vulvar neoplasia studied at the Istituto Nazionale Tumori of Milan, 62% appeared to be related to papillomavirus infection. This conclusion is the result of the present study by in situ hybridization with DNA probes of human papillomavirus (HPV) 6/11, 16, and 18 and of previous ultrastructural and immunohistochemical investigations. The proportion of cases associated with HPV was 78.5% for those (11/14) with histologic evidence of viral infection and 33% for those without (2/6). HPV 16 was detected in all cases that were positive by in situ hybridization except for one, which showed HPV 6/11 DNA. In one case there was a mixed triple infection for HPV 6/11, 16, and 18. The patient who was positive for HPV 6/11 had a giant condyloma associated with an inguinal lymph node containing a metastatic well-differentiated squamous cell carcinoma. Three cases were positive for papillomavirus internal capsid species-nonspecific antigen (PV-Ag) (with ultrastructural evidence of virions in one of them) and were negative for HPV-DNA hybridization. They appeared to be infected with a type of HPV not identified by the available probes. Three cases, and two sites of two other cases with double infection, were HPV-DNA-positive and PV-Ag-negative. They illustrate the limitation of immunohistochemical investigation in cases with high-grade intraepithelial neoplasia. Six cases of verrucous carcinoma of the vulva were negative for HPV DNA by in situ hybridization.     

Detection of human papillomavirus DNA in cancer of the urinary bladder by in situ hybridisation.

The association of the human papillomavirus (HPV) with cancer of the urinary bladder was assessed by in situ hybridisation using probes selective for HPV types 6/11 and 16/18 DNA. No hybridisation signal was detected with the type 6/11 probe on 100 formalin-fixed, paraffin-embedded bladder tumours sampled. However, when the same samples were hybridised with the HPV type 16/18 DNA probe, 11 of 66 (16.6%) papillary and 1 of 10 (10%) solid transitional cell carcinomas gave positive signals. These results suggest the involvement of HPV in cancer of the bladder, although the frequency of multiple HPV types in these tumours is uncertain.     

阴茎尖锐湿疣人乳头状瘤病毒聚合酶链反应（PCR）检测

应用聚合酶链反应（ＰＣＲ），检测３４例男性生殖器尖锐湿疣标本中ＨＰＶ６．１１型病毒。结果显示：在２０例具有典型病理特征（空泡细胞）和１４例组织学特征非典型标本中均检出ＨＰＶ６．１１型病毒。表明ＰＣＲ是诊断尖锐湿疣快速，简便，高敏感和特异性强的方法     

Verruca vulgaris of the vulva in children and adults: a nonvenereal type of vulvar wart

Condyloma acuminata are common lesions of the vulva in adults, and associated with infection by human papillomavirus (HPV) types 6 and 11, which are acquired via sexual contact. The detection of an HPV 6/11 condyloma in the genital tract of a child, therefore, raises the question of sexual abuse. In this study, 29 genital warts in girls less than 5 years of age were examined for nongenital and genital tract HPVs by in situ hybridization. These results were compared with 275 vulvar lesions clinically suspicious for condyloma from adults. Of the 27 HPV-related lesions in young girls, 11 (41%) were due to HPV 2 whereas the other 16 (59%) were associated with HPV 6/11 infection. Of the 214/275 (78%) HPV positive vulvar lesions in adults, 6 (3%) were due to HPV 2 whereas 202/214 (94%) contained HPVs 6/11; 1 lesion contained HPV 16 and the 5 other lesions contained HPV 42, 43, or 44. Histologic correlation documented that the vulvar lesions positive for HPV 2 commonly showed the marked hyperkeratosis typical of verruca vulgaris. However, the verrucous pattern was present in lesions HPV 6/11 positive. It is concluded that verruca vulgaris of the vulva, which is likely not transmitted sexually, can occur, albeit rarely, in the genital tract of women and is common in the genital tracts of young girls. This highlights the value of HPV testing in such cases, especially if the histologic changes are consistent with verruca vulgaris.     

Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR)

Human papillomavirus (HPV) infections are strongly linked to the pathogenesis of uterine cervical neoplasms, and have been implicated in other cancers of the female genital tract. In contrast, the association of HPV with the cancers of the male urogenital tract is less evident, except in anal and penile cancers. However, recent studies reporting the prevalence of HPV infections in human prostate cancers (60–100% HPV 16 positive vs. no infection of HPV) have raised controversies regarding the prevalence of HPV in benign and neoplastic human prostate. We investigated the prevalence of HPV infections in prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinomas in 23 surgically resected prostates. Polymerase chain reaction (PCR) was used to amplify HPV 6b/11, 16 and 18 specific DNA sequences, using type specific HPV primers selected from the transforming gene E6-E7. The areas of PIN and cancer in 6 p.m H&E stained tissue sections were identified, and respective areas of PIN and cancer were isolated from the adjacent serial sections and used for DNA amplification and HPV detection (Fig. 1). Our results demonstrated the presence of HPV 16 in three carcinomas (13%), using type specific primers in PCR amplified samples. We were not able to demonstrate the presence of other HPV types (HPV 6b/11 or HPV 18) in any of the samples using specific primers. Two of these prostates showed relatively strong positive signals by dot blot analysis, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. One more sample showed weak positivity, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. Subsequently, we have confirmed these results by Southern hybridization of the samples transferred to nylon membrane after agarose gel electrophoresis and detected by HPV 16 type specific oligonucleotide probe, using chemiluminescent assay. We, therefore, conclude that HPV infections of the prostate in general are not as common as has been previously claimed by other investigators. © 1993 Wiley-Liss, Inc.     

Correlation of histology and human papillomavirus DNA detection in condyloma acuminatum and condyloma-like vulvar lesions

The diagnosis of a vulvar condyloma is made when perinuclear halos are seen with nuclear atypia and binucleate forms (koilocytotic atypia). These changes are most prominent in the granular layer and are associated with the presence of human papillomavirus (HPV). However, these changes may be absent or minimal in patients with papillary vulvar lesions; this situation can thus present diagnostic difficulties. We analyzed the histologic features of 53 biopsies from 48 patients who had vulvar lesions suggestive of condylomata. Of the 26 biopsy specimens with koilocytotic atypia, 20 (77%) had sequences homologous to HPV DNA as detected by Southern blot hybridization analysis using a probe of HPV s 6/11, 16, 18, 31, 35, and 51. In cases where the histologic features were suggestive but not diagnostic of condylomata, because unequivocal koilocytotic atypia was not noted, five of 27 (19%) had detectable HPV DNA. In this latter group, we found no histologic feature to distinguish the cases that had detectable HPV DNA from those that did not. Analysis for HPV DNA by in situ hybridization in the cases that were histologically equivocal for condyloma was uniformly negative. We conclude that there is a marked decrease in the detection rate of the HPV types associated with genital tract neoplasms in vulvar lesions that lack koilocytotic atypia. Southern blot hybridization analysis was the only reliable way to distinguish the "equivocal for condyloma" cases that had HPV from those where HPV DNA was not detected.     

阴茎癌组织中人乳头瘤病毒DNA的原位杂交研究

为了研究人乳头瘤病毒与阴茎癌的关系，应用地高辛标记的ＨＰＶ６、ＨＰＶ１１、ＨＰＶ１６和ＨＰＶ１８ＤＮＡ探针分别对４６例阴茎癌组织进行原位杂交检测ＨＰＶＤＮＡ。结果显示：ＨＰＶＤＮＡ阳性２２例，其中ＨＰＶ１６ＤＮＡ阳性２０例，ＨＰＶ１８ＤＮＡ阳性４例，在２例转移癌和癌旁不典型增生组织中检测到了ＨＰＶ１６ＮＤＡ，未见ＨＰＶ６ＤＮＡ和ＨＰＶ１１ＤＮＡ阳性，ＨＰＶＤＮＡ位于癌细胞核中。结果表明原位杂交可以用来研究阴茎癌组织中ＨＰＶ的存在及分型，同时也证实了阴茎癌的发生和ＨＰＶ１６及ＨＰＶ１８感染有密切关系     

Clinical study of serum squamous cell carcinoma-related antigen levels in penile cancer

A squamous cell carcinoma-related antigen (SCC-Ag), which has been recognized as a tumor marker of cervical cancer of the uterine, was detected in the serum with a radioimmunoassay and its clinical usefulness in penile cancer was evaluated. Seven serum samples of penile cancer, one of Paget's disease and two of condyloma acuminatum were analyzed for the SCC-Ag level. The mean +/- standard deviation of serum SCC-Ag level and positive rate (greater than 2.0 ng/ml) were 1.6 +/- 1.75 ng/ml and 14%. Neither pathological staging nor cell grading of penile cancer showed any relation to the serum SCC-Ag level. When the tumor of the penis has been recognized and a cut-off value of 1.0 ng/ml used, the positive rate of penile cancer was 71.4% and false positive rate of other benign penile tumors was 0%. Serum SCC-Ag values were changed parallel in to the clinical course in three patients. These results suggest that the detection of the serum SCC-Ag value may be of use for detection of penile cancer and monitoring of these patients.     

Anal cloacogenic and squamous carcinomas. Comparative histologic analysis using in situ hybridization for human papillomavirus DNA

In order to evaluate the morphologic and possible etiologic distinctions between anal cloacogenic and squamous carcinomas, we performed histologic examination and in situ hybridization for human papillomavirus (HPV) DNA on anal canal and anal verge carcinomas from 37 patients. Twenty-one neoplasms were invasive or in situ squamous carcinomas, 14 were invasive cloacogenic carcinomas, and two were unclassified. In situ hybridization was positive for HPV types 16/18 in 12 cases and for types 6/11 in two cases of anal squamous carcinoma (67% HPV positivity overall). All 14 cases classified as anal cloacogenic carcinoma were negative for HPV DNA by this technique. One of the two unclassified carcinomas was positive for type 16/18 DNA. We conclude that anal cloacogenic and squamous carcinomas are histologically similar but distinct neoplasms. Differential expression of HPV DNA in these lesions may be a manifestation of separate mechanisms of pathogenesis, or it may be due to varying degrees of tumor cell differentiation.     

64例合并HIV感染男男性行为者肛门直肠尖锐湿疣临床特征及心理评估

目的探讨合并人类免疫缺陷病毒（HIV）感染的男男性行为（MSM）人群发生肛门直肠尖锐湿疣的临床特征及心理状态。 方法分析2015年7月至2017年6月于四川洲际胃肠肛门病医院住院治疗的64例合并HIV感染的男男性行为人群中发生肛门直肠尖锐湿疣患者临床特征以及90项症状清单（SCL-90）量表心理评估情况。 结果合并HIV感染的MSM人群中，肛周直肠尖锐湿疣主要见于18～45岁男性（61例，84.72%），其中大学学历患者47例（73.44%）；经典型尖锐湿疣患者56例（87.50%），扁平型尖锐湿疣患者8例（12.50%）。人乳头状瘤病毒（HPV）阳性率为81.25%（52例，52/64），以HPV11型为主（占50.00%，26/52）。SCL-90量表心理评估显示，负面心理情绪患者59例（92.19%），主要表现为抑郁（48例、75.0%）和焦虑（7例、10.94%）。 结论合并HIV感染的MSM人群中，肛周直肠尖锐湿疣主要见于青壮年，临床表现以经典型为主，心理状态以抑郁、焦虑为主。     

A "Pap" test for men? Male urethral smears as screening tool for detecting subclinical human papillomavirus infection.

We have explored the potential of using immunoperoxidase staining and in situ DNA hybridization techniques to detect the HPV common antigen and HPV DNA (subtypes 6/11 and 16/18) in urethral smears obtained from men with no grossly visible urethral lesions, with or without HPV-related clinical history. A total of 91 such smears were studied of which 25 (27.5%) were positive for HPV antigen. Of the latter, 20 (80%) were positive for HPV 6/11 DNA, 3 (12%) were positive for HPV 16/18 DNA, one smear (4%) was positive for both, and one was negative for both. The technique of obtaining male urethral smears and immunostaining them for HPV antigen is simple, rapid, specific, and far more sensitive than conventional morphologic observations. Since antigen-positive cells are the source for spreading HPV infection, identifying individuals with such cells can help limit the spread of infection by alerting sexual partners, and also can be used to monitor the infectious status of the patient after therapy. DNA subtyping of HPV-positive patients may be useful in predicting the potential for malignant transformation which varies among the different HPV subtypes.     

某院1 715例妇科就诊者人乳头瘤病毒感染率及基因型分布

目的分析妇科就诊人群人乳头瘤病毒(HPV)感染率及基因型分布,为宫颈癌的诊治及HPV疫苗的研制提供参考。 方法采用凯普医用核酸分子快速导流杂交基因芯片技术(Hybrimax)检测2009年11月至2016年10月宝鸡市中医医院门诊及住院的1 715例自愿接受生殖道HPV感染筛查且有性生活史妇女的21种HPV基因型别。 结果就诊人群宫颈感染HPV高危型以HPV58、HPV16、HPV52和HPV33型最为常见,而HPV低危型则以HPV11及CP8304为主。1 715例就诊者中266例HPV阳性,阳性率为15.51%。其中单一感染者168例(9.80%),双重及多重感染者98例(5.71%);就诊者以31～40岁和41～50岁年龄段HPV感染率较高,分别为18.31%和18.60%;其次为≤30岁就诊者,感染率为13.92%;>50岁患者HPV感染率较低(8.24%),与≤30岁患者相比差异具有统计学意义(P均<0.05)。168例单一高危型HPV感染者以HPV58、HPV16、HPV52、HPV33型感染为主,分别为68例(40.48%)、40例(23.81%)、22例(13.10%)、10例(5.95%),与HPV58型阳性率比较,HPV16、HPV52、HPV33型的阳性率差异均有统计学意义(P均<0.05);低危型HPV感染者以HPV11型和CP8304感染为主,分别为16例(9.52%)和12例(7.14%),差异无统计学意义(χ²= 1.512、P= 0.186)。98例双重及多重HPV感染者中双重感染者62例(63.27%);三重感染者28例(28.57%);四重感染者8例(8.16%)。双重及多重HPV感染亚型主要以HPV58、HPV16、HPV52和HPV11型为主,分别为25例(25.51%)、20例(20.41%)、16例(16.33%)和11例(11.22%)。 结论本院妇科就诊人群高危型HPV感染率基本符合亚洲人群分布规律,但存在一定区域性。     

MIB-1 immunostaining is a beneficial adjunct test for accurate diagnosis of vulvar condyloma acuminatum

The histopathologic diagnosis of vulvar condyloma acuminatum is often based on architectural features that are not specific for human papillomavirus (HPV) infection. Because HPV-associated lesions show increased cellular proliferation, the authors evaluated the usefulness of MIB-1 immunostaining as an aid in the differential diagnosis of cases equivocal for condyloma. The MIB-1 immunostaining pattern was correlated with HPV DNA detection in condyloma acuminatum (CON-A; n = 15), "consistent with condyloma" (c/w CON-A; n = 26), fibroepithelial polyp (FEP; n = 14), and squamous papilloma (n = 10). HPV was detected in 100% of the CON-A cases, and all cases demonstrated MIB-1-positive nuclei in the upper two thirds of the epithelial thickness. With this definition of MIB-1 positivity, there was complete concordance between MIB-1 positivity and HPV detection for all cases (kappa = 0.88). Of the cases c/w CON-A, 17 of 26 (65%) were positive for both MIB-1 and HPV, and could be reclassified as CON-A, whereas 35% were identified as an overdiagnosis based on negative results. In addition, two cases of FEP were MIB-1 and HPV positive, and thus were identified as an underdiagnosis. These results suggest significant overdiagnosis of cases equivocal for condyloma, and indicate that MIB-1 immunostaining is a beneficial adjunctive test when the morphologic features are suggestive but not diagnostic for CON-A.     

Low frequency of human papillomavirus infection in initial papillary bladder tumors

The involvement of human papillomavirus (HPV) in bladder cancer remains controversial. We previously reported detection of L1-HPV DNA in 39% of bladder cancers of mixed grade and stage. To clarify the possible etiologic role of HPV we studied, using the same technique, a more homogeneous group of initial low-stage tumors. We investigated a total of 187 newly diagnosed superficial papillary bladder tumors for the presence of L1-HPV DNA by the polymerase chain reaction method and hybridization with specific probes for HPV 6, 11, 16, 18, 33. HPV DNA was detected in 16 (8.5%) of the 187 specimens tested, although in a low copy number compared with SiHa cervical cancer cells used as control. HPV type 16 was observed in eight tumors while HPV type 6 and type 11 were each observed in three tumors. Two tumor specimens contained two types of HPV: one tumor hybridized with type 6 and 16 and the other with type 11 and 18. This low rate of HPV detection (8.5%) in initial tumors does not favor a prominent role for HPV in bladder carcinogenesis. Received: 7 September 1998 / Accepted: 7 December 1998     

Giant condyloma with malignant degeneration: a case report

We report a case of giant condyloma with malignant degeneration. A 56-year-old male was referred to our hospital due to a penile infection that was resistant to antibiotic therapy for more than a year. The swelling appeared to be a penile cancer. We suspected malignancy and performed penile biopsies twice; however, the histopathological diagnosis was condyloma acuminatum and malignant findings were absent. We continued the antibiotic therapy for 3 months; however, no improvement was achieved. Therefore, total penectomy and urinary diversion were performed. The pathological diagnosis of the resected tissues was not only condyloma but also squamous cell carcinoma, and cancer cells appeared on the cut surface of the specimens. We added radiation therapy. There was no evidence of recurrence or metastasis at 18 months after surgery.     

Association between urothelial carcinoma after renal transplantation and infection by human papillomavirus types 16 and 18

Objective

To explore the association between urothelial carcinoma following renal transplantation and infection by human papillomavirus (HPV) types 16 and 18.

Materials and Methods

Of 3780 patients who underwent renal transplantation, we identified 90 cases of urothelial carcinoma. Tumor tissues collected from the 90 renal transplant recipients were compared with those from 30 nontransplanted patients with bladder cancer (control group) for HPV types 16 and 18 using polymerase chain reactions.

Results

Seven transplanted patients were HPV positive: HPV-16 was detected in 3 patients with bladder cancer (3/90; 3.3%), and HPV-18 in 2 patients with bilateral pelvic ureteral carcinoma (2/90; 2.2%), and 2 patients with bladder cancer (2/90; 2.2%). Only 2 cases from the control group were HPV positive (both HPV-18; 2/30; 5%). The difference between the RTR and control groups was not significant (P > .05).

Conclusion

Malignant tumors in the urinary system following renal transplantation did not seems to be associated with infection by HPV-16 or -18.     

Basaloid squamous cell carcinoma of the penis with papillary features: a clinicopathologic study of 12 cases

There are 3 distinct variants of penile squamous cell carcinoma frequently associated with human papillomavirus (HPV): basaloid, warty-basaloid, and warty carcinomas. Considering the high incidence rates of penile cancer in some countries, a large international study was designed to evaluate the presence of HPV, its genotype distribution, and its association with histologic types of penile cancer. In this international review of >900 cases, we found a group of highly distinct papillary neoplasms composed of basophilic cells resembling urothelial tumors but frequently associated with HPV. Macroscopically, tumors were exophytic or exoendophytic. Microscopically, there was a papillomatous pattern of growth with a central fibrovascular core and small basophilic cells lining the papillae. Positivity for HPV was present in 11 of 12 tumors (92%). Single genotypes found were HPV-16 in 9 tumors and HPV-51 in 1 tumor. Multiple genotypes (HPV-16 and HPV-45) were present in another case. Overexpression of p16 was observed in all cases. Uroplakin-III was negative in all cases. The differential diagnosis was with basaloid, warty-basaloid, warty, and papillary squamous cell carcinoma and with urothelial carcinomas. Local excision (4 cases), circumcision (3 cases), or partial penectomy (5 cases) were preferred treatment choices. Tumor thickness ranged from 1 to 15 mm (average, 7 mm). Two patients with tumors invading 11 and 15 mm into the corpus spongiosum developed inguinal nodal metastasis. Of 11 patients followed up (median 48 mo), 7 were alive with no evidence of metastatic disease, 3 died from causes other than penile cancer, and another died postoperatively. This morphologically distinct tumor probably represents a papillary variant of basaloid carcinomas (papillary-basaloid carcinomas). Unlike typical basaloid carcinomas, the overall prognosis was excellent. However, deeply invasive tumors were associated with regional nodal metastasis indicating a potential for tumor-related death.