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Detection of the human papillomavirus in cervical carcinoma: a comparison between non-isotopic in-situ hybridisation and polymerase chain reaction as methods for detection in formalin-fixed, paraffin-embedded tissues

Cheah PL, Looi LM

Malays J Pathol, 2008 Jun;30(1):37-42.
PMID: 19108410

Cervical carcinoma, the second most common malignancy in Malaysian females, is aetiologically linked to the human papillomavirus (HPV). A study was conducted at the Department of Pathology, University of Malaya Medical Centre to compare the identification of HPV 6, 11, 16 and 18 in 40 archived formalin-fixed, paraffin-embedded cervical carcinoma by non-isotopic in-situ hybridisation (NISH) and polymerase chain reaction (PCR). HPV L1 ORF consensus PCR was also carried in cases which were negative on HPV type-specific PCR. NISH detected HPV 16 in 13 (32.5%) cases with one case demonstrating a concomitant HPV 18. beta-globin DNA PCR was carried out on the same paraffin block as for NISH in 27 cases and on a different paraffin block in 13, with amplification in 9 of the former and 3 of the latter. Thus only 12 cases were subjected to further HPV PCR. HPV was detected in 10 (83.3%) with HPV 16 in 9 cases and HPV L1 ORF in one. When using the same paraffin block for both methods of HPV detection, NISH detected HPV in 6 and PCR in 7. NISH failed to detect HPV in a case detected by PCR. 2 cases were negative for HPV using both methods. Hence, HPV detection results by NISH and PCR were concordant in 88.9%. Interestingly, NISH detected HPV in 2 cases with non-amplifiable beta-globin DNA. Using an alternative paraffin block for HPV PCR from NISH, HPV DNA was detected in 3 cases, two of which also showed type-specific positivity on NISH. The third case did not reveal type-specific positivity with NISH or PCR but demonstrated HPV DNA on L1 ORF consensus PCR. It thus appears that PCR and NISH can be successfully used to detect HPV in formalin-fixed, paraffin-embedded tissue and in the presence of intact DNA NISH may be as sensitive as PCR.

Matched MeSH terms: Human papillomavirus 6/isolation & purification
Fulltext Global genomic diversity of human papillomavirus 6 based on 724 isolates and 190 complete genome sequences

Jelen MM, Chen Z, Kocjan BJ, Burt FJ, Chan PK, Chouhy D, et al.

J Virol, 2014 Jul;88(13):7307-16.
PMID: 24741079 DOI: 10.1128/JVI.00621-14

Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated the global genomic diversity of HPV6, using 724 isolates and 190 complete genomes from six continents, and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples collected for this study. Among them, 130 exhibited at least one single nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full. A global alignment and maximum likelihood tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60 obtained from sequence repositories) revealed two variant lineages, A and B, and five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within the L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America, and lineage A was more common in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, a global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender, and/or disease predilection in their distribution.
IMPORTANCE: This study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new, complete HPV6 genome sequences to available sequence repositories. Two HPV6 variant lineages and five sublineages were identified and showed some degree of association with geographical location, anatomical site of infection/disease, and/or gender. We additionally identified several HPV6 lineage- and sublineage-specific SNPs to facilitate the identification of HPV6 variants and determined a representative region within the L2 gene that is suitable for HPV6 whole-genome-based phylogenetic analysis. This study complements and significantly expands the current knowledge of HPV6 genetic diversity and forms a comprehensive basis for future epidemiological, evolutionary, functional, pathogenicity, vaccination, and molecular assay development studies.

Matched MeSH terms: Human papillomavirus 6/genetics*; Human papillomavirus 6/isolation & purification*
Fulltext Penile warts: an update on their evaluation and management

Leung AK, Barankin B, Leong KF, Hon KL

Drugs Context, 2018;7:212563.
PMID: 30622585 DOI: 10.7573/dic.212563

Background: Penile warts are the most common sexually transmitted disease in males. Clinicians should be familiar with the proper evaluation and management of this common condition.
Objective: To provide an update on the current understanding, evaluation, and management of penile warts.
Methods: A PubMed search was completed in Clinical Queries using the key terms 'penile warts' and 'genital warts'. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews.
Results: Penile warts are caused by human papillomavirus (HPV), notably HPV-6 and HPV-11. Penile warts typically present as asymptomatic papules or plaques. Lesions may be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, fungating, or cauliflower-like. Approximately one-third of penile warts regress without treatment and the average duration prior to resolution is approximately 9 months. Active treatment is preferable to watchful observation to speed up clearance of the lesions and to assuage fears of transmission and autoinoculation. Patient-administered therapies include podofilox (0.5%) solution or gel, imiquimod 3.75 or 5% cream, and sinecatechins (polypheron E) 15% ointment. Clinician-administered therapies include podophyllin, cryotherapy, bichloroacetic or trichloroacetic acid, oral cimetidine, surgical excision, electrocautery, and carbon dioxide laser therapy. Patients who do not respond to first-line treatments may respond to other therapies or a combination of treatment modalities. Second-line therapies include topical/intralesional/intravenous cidofovir, topical 5-fluorouracil, and topical ingenol mebutate.
Conclusion: No single treatment has been shown to be consistently superior to other treatment modalities. The choice of the treatment method should depend on the physician's comfort level with the various treatment options, the patient's preference and tolerability of treatment, and the number and severity of lesions. The comparative efficacy, ease of administration, adverse effects, cost, and availability of the treatment modality should also be taken into consideration.

Matched MeSH terms: Human papillomavirus 6
Fulltext Detection of human papillomavirus, p53 and c-erbb-2 protein expression in juvenile laryngeal papillomatosis: a report of 2 cases

Siti Aishah Md Ali, Ilina Isahak, Dahlan Sabi, Fatimah Sahlan, Lokman Saim, Abdullah Sani Mohamed

Medicine & Health, 2006;1(1):67-74.
MyJurnal

The association of human papillomavirus (HPV) with juvenile laryngeal papillomatosis has been well documented. We report two cases of juvenile laryngeal papillomatosis and correlated these cases with presence of HPV, p53 and c-erbB-2 proteins. The first case was a one-year-old male patient and the second a six-year-old female patient. Formalin-fixed paraffin-embedded biopsy specimens were tested for the presence of HPV genome by the technique of in situ hybridisation using wide spectrum and type specific biotinylated probes while the immunohistochemical expression of p53 (D07, 1:50) and c-erbB-2 (DAKO A0485, 1:300) proteins were evaluated with commercially available antibodies. Histologically the tumours in both cases showed papillary configuration of squamous papilloma. The first case detected HPV type 6, HPV type 11 and p53 protein expression while the second case showed only HPV type 6. Both cases of HPV showed positive signals confined to the nuclei in the superficial squamous epithelium. The first case showed p53 positivity seen from the basal region up to one third of the epithelium of laryngeal papillomas and the subsequent recent repeat biopsy showed the positivity of p53 had extended throughout the upper layers of the epithelium. Expression of c-erbB-2 protein was not detected in both cases. These findings were similar as in other studies where follow-up of the cases was recommended since they tend to recur.

Matched MeSH terms: Human papillomavirus 6