The acetic acid test in evaluation of subclinical genital papillomavirus infection: a comparative study on penoscopy, histopathology, virology and scanning electron microscopy findings.
OBJECTIVE
To evaluate colposcopic criteria in acetowhite lesions of the penis ("penoscopy") for the diagnosis of subclinical genitoanal papillomavirus infection (GPVI) compared with histopathological criteria of HPV involvement and to various hybridisation assays for HPV DNA detection, and to depict typical lesions by scanning electron microscopy.


METHODS
The study included 101 randomly selected male partners of females with known GPVI, or with penile symptoms such as itching, burning and dyspareunia who did not exhibit overt genital warts but appeared to be afflicted with acetowhite penile lesions after topical application of 5% acqueous acetic acid. Lesions were judged by penoscopy as either typical, conspicuous or nontypical for underlying HPV infection. Biopsy specimens from 91 men were examined by light microscopy and by either Southern blot (SB), polymerase chain reaction (PCR) and/or in situ hybridisation (ISH) assays for the presence of HPV DNA of the HPV types 6, 11, 16, 18, 31, 33 and 42 (Group A). From another ten men lesions clinically typical for GPVI were also examined topographically by scanning electronic microscopy (Group B).


METHODS
The STD out-patient clinic of the Department of Dermatovenereology of Karolinska Hospital, Stockholm, Sweden.


RESULTS
Group A Seventy eight (86%) of the biopsied lesions met the penoscopy criteria of being either typical of or conspicuous for GVPI. The agreement between penoscopy and histopathology was fairly good, as HPV diagnosis was made by both methods in 56 (62%) of the cases. The reliability of applying strict colposcopic hallmarks was further substantiated by the finding that 55 (60%) of the biopsy specimens taken from penoscopically typical/conspicuous lesions contained HPV DNA. However, there are diagnostic pitfalls for the acetic acid test. Coexistence of an eczematoid reaction with changes indicative of HPV influence was detected in six (7%) of the cases, while an inflammatory response only occurred in 17 (19%) of the specimens. Additional histopathological diagnoses (normal epithelium, lichen sclerosus et atrophicus, balanitis circinata parakeratotica, verruca plana) were established in another eight (9%) of the cases. Among the HPV DNA positive cases, all of the HPV types tested for were detected with the exception of HPV 18. A severe penile intraepithelial neoplasia (PIN III) was revealed in five (5%) of biopsies; HPV 16 was present in two and HPV 42 in one of these biopsy specimens.
Scanning electron microscopy depiction harmonised with the penoscopy findings showing that subclinical GPVI characteristically exhibits a well demarcated, slightly elevated border and that the central area of lesions often displays a "groove" in which the epithelium appears to be thin with protrusions from beneath that probably represent capillaries.


CONCLUSIONS
Use of the acetic acid test for evaluation of GPVI should be combined with a colposcopic evaluation based on strict topographic hallmarks, followed by a directed biopsy for light microscopic evaluation. We found that the positive predictive value of colposcopy was as high when correlated with histopathological findings (72%) as when virological methods were used, whether HPV DNA hybridisation testing was performed with the well established SB and ISH assays (45%), or by applying the newly introduced and highly sensitive PCR assay as well (71%). False positivity from the acetic acid test occurs and is mainly due to inflammatory conditions but also to the presence of other conditions. Epithelial fissures are evidently associated with some subclinical GPVI lesions and may potentially represent loci minores for infectious stimuli and perhaps facilitate the transmission of some blood-borne STDs. We prose that the term "papillomavirus balanoposthitis" should be used for penile HPV infection associated with inflammatory responses. Our study indicates that PIN III frequently occurs in a subclinical form and may be associated with not only previously identified "high-risk" HPV types such as type 16, but also with the HPV type 42 that has not previously been considered as oncogenic.
Wikström
A
A
Department of Dermatovenereology, Karolinska Hospital, Stockholm, Sweden.
Hedblad
M A
MA
Johansson
B
B
Kalantari
M
M
Syrjänen
S
S
Lindberg
M
M
von Krogh
G
G
D000085:Acetates; D019342:Acetic Acid; D015139:Blotting, Southern; D004724:Endoscopy; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D027383:Papillomaviridae; D010409:Penile Diseases / Q000175:diagnosis* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D014412:Tumor Virus Infections / Q000175:diagnosis* / Q000473:pathology
D000085:Acetates; D019342:Acetic Acid