Association of human papillomavirus with penile carcinoma: A study using polymerase chain reaction and in situ hybridization

doi:10.1016/0046-8177(91)90181-N

Human Pathology

Volume 22, Issue 9, September 1991, Pages 908-913

https://doi.org/10.1016/0046-8177(91)90181-N Get rights and content

Abstract

Although carcinoma of the uterine cervix has been shown to be strongly associated with human papillomavirus (HPV) infection, a sexually transmitted disease, similar detailed data are lacking in penile carcinoma. To determine the association of HPV with penile carcinoma, we examined 30 specimens of penile carcinoma from 23 patients by the highly sensitive polymerase chain reaction (PCR) and in situ hybridization assays. We also examined nonneoplastic penile foreskins from 20 adults using the polymerase chain reaction assay. Human papillomavirus type 16 genome was found in 15 patients (65%), HPV type 30 was found in three (13%), and HPV type $611$ was found in two (9%). These HPV types were not detected in any of the nonneoplastic foreskins. As in cervical carcinoma, HPV, particularly type 16, is strongly associated with penile carcinoma and may play an etiologic role in the development of this neoplasm.

References (23)

A Schneider et al.
Subclinical human papillomavirus infections in male sexual partners of female carriers
J Urol
(1988)
K.B. Mullis et al.
Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction
Methods Enzymol
(1987)
E.M. de Villiers
Heterogeneity of the human papillomavirus group
J Virol
(1989)
P.M. Howley et al.
The human papillomaviruses: An overview
Am J Med
(1988)
M.J. Campion et al.
Human papillomavirus and anogenital neoplasia: A fresh look at the association
South Med J
(1989)
P.M. Katerlaris et al.
Human papillomavirus: The untreated male reservoir
J Urol
(1988)
M.E. Boon et al.
Penile studies and heterosexual partners
Cancer
(1988)
M.J. Campion et al.
Subclinical penile human papillomavirus infection and dysplasia in consorts of women with cervical neoplasia
Genitourin Med
(1988)
L Kennedy et al.
Human papillomavirus: A study of male sexual partners
Med J Aust
(1988)
L Pensky
Epidemiology of cancer of the penis: Recent results
Cancer Res
(1977)

D.K. Shibata et al.

Detection of human papilloma virus paraffin-embedded tissue using the polymerase chain reaction

J Exp Med

(1988)

Cited by (50)

Prevalence of human papillomavirus DNA and p16 <sup>INK4a</sup> in penile cancer and penile intraepithelial neoplasia: a systematic review and meta-analysis
2019, The Lancet Oncology
Although previous meta-analyses have examined human papillomavirus (HPV) DNA prevalence in penile cancer, none, to our knowledge, have assessed pooled HPV DNA prevalence in penile intraepithelial neoplasia or p16^INK4a percent positivity in penile cancer and penile intraepithelial neoplasia. Therefore, we aimed to examine the prevalence of HPV DNA and p16^INK4a positivity in penile cancer and penile intraepithelial neoplasia worldwide.
In this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library until July 24, 2017, for English-language articles published from Jan 1, 1986, onwards reporting the prevalence of HPV DNA and p16^INK4a positivity, either alone or in combination, in at least five cases of penile cancer or penile intraepithelial neoplasia. Only studies that used PCR or hybrid capture for the detection of HPV DNA and immunohistochemical staining or methylation for the detection of p16^INK4a were included. Data were extracted and subsequently crosschecked, and inconsistencies were discussed to reach consensus. Using random-effects models, we estimated the pooled prevalence and 95% CI of HPV DNA and p16^INK4a positivity in penile cancer and penile intraepithelial neoplasia, stratifying by histological subtype and HPV DNA or p16^INK4a detection method. Type-specific prevalence of HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, and HPV45 in penile cancer was estimated.
Our searches identified 1836 non-duplicate records, of which 73 relevant papers (71 studies) were found to be eligible. The pooled HPV DNA prevalence in penile cancer (52 studies; n=4199) was 50·8% (95% CI 44·8–56·7; I²=92·6%, p_{heterogeneity}<0·0001). A high pooled HPV DNA prevalence was seen in basaloid squamous cell carcinomas (84·0%, 95% CI 71·0–93·6; I²=48·0%, p_{heterogeneity}=0·0197) and in warty-basaloid carcinoma (75·7%, 70·1–81·0; I²=0%, p_{heterogeneity}=0·52). The predominant oncogenic HPV type in penile cancer was HPV16 (68·3%, 95% CI 58·9–77·1), followed by HPV6 (8·1%, 4·0–13·7) and HPV18 (6·9%, 2·9–12·4). The pooled HPV DNA prevalence in penile intraepithelial neoplasia (19 studies; n=445) was 79·8% (95% CI 69·3–88·6; I²=83·2%, p_{heterogeneity}<0·0001). The pooled p16^INK4a percent positivity in penile cancer (24 studies; n=2295) was 41·6% (95% CI 36·2–47·0; I²=80·6%, p_{heterogeneity}<0·0001), with a high pooled p16^INK4a percent positivity in HPV-related squamous cell carcinoma (85·8%, 95% CI 72·1–95·4; I²=56·4%, p_{heterogeneity}=0·0011) as compared with non-HPV-related squamous cell carcinoma (17·1%, 7·9–29·1; I²=78·3%, p_{heterogeneity}<0·0001). Moreover, among HPV-positive cases of penile cancer, the p16^INK4a percent positivity was 79·6% (95% CI 65·7–90·7; I²=89·9%, p_{heterogeneity}<0·0001), compared with 18·5% (9·6–29·6; I²=89·3%, p_{heterogeneity}<0·0001) in HPV-negative penile cancers. The pooled p16^INK4a percent positivity in penile intraepithelial neoplasia (six studies; n=167) was 49·5% (95% CI 18·6–80·7).
A large proportion of penile cancers and penile intraepithelial neoplasias are associated with infection with HPV DNA (predominantly HPV16), emphasising the possible benefits of HPV vaccination in men and boys.
None.
Infections of the Genital Tract: Human Papillomavirus–Related Infections
2017, European Urology, Supplements
Citation Excerpt :
There is presently no scientific explanation why HPV-negative patients should have lower cancer-specific survivals. No correlation between HPV presence and survival could be found in two further studies [100–113]. The economic burden of HPV disease in individuals aged 15–24 yr has been estimated at nearly US $3 billion in America alone, with an estimated $200 million spent annually in direct medical costs just for genital wart treatment [114,115].
The human papillomaviruses (HPVs) are a major global health burden, playing a part in diseases ranging from genital warts to malignancies such as penile cancer in men and cervical cancer in women.
To explore the molecular biology and epidemiology of HPV infection; the diseases linked to it; and current prevention strategies, including the potential role of vaccination.
The relevant papers, reviews, and guidelines pertaining to the topics were collected for the purpose of this review from PubMed and online guidelines resources including the European Association of Urology and the Centers for Disease Control and Prevention.
The current knowledge on genital HPV in men is explained and summarised.
There is an urgent need for more data on the incidence and persistence of HPV at the different anatomic sites, the incidence of external genital lesions, and the types of HPV in these lesions. This will allow a more comprehensive understanding of the natural history of HPV infection and its progression to both benign and malignant disease in men and will help formulate the development and implementation of vaccination programs.
This review explores the molecular biology and epidemiology of human papillomavirus (HPV) infection; the diseases linked to it; and current prevention strategies, including the potential role of vaccination. There is an urgent need for more data on the incidence and persistence of HPV at the different anatomic sites, the incidence of external genital lesions, and the types of HPV in these lesions.
Epidemiology of penile cancer
2015, Current Problems in Cancer
Citation Excerpt :
A major risk factor for penile cancer is infection with HPV, the risk of which increases with the number of sexual partners, a history of genital warts, and concomitant sexually transmitted diseases. The estimated overall prevalence of HPV in penile cancer is between 42% and 48% with the most commonly involved HPV subtypes being HPV 16 and 18, as shown in Fig 6.18-31 Some penile cancer subtypes are more commonly associated with HPV, such as basaloid (80%) and warty tumors (100%).
Epidemiology and natural history of penile cancer
2010, Urology
Citation Excerpt :
High-risk HPV has been detected in 24%-65% of penile cancer cases compared with 12% of controls.8,13,32,33 Specifically, penile carcinoma is associated with HPV-16 in 25%-94.7% and HPV-18 in 10.5%-55.4% of cases (Table 3).11,29,34-38 At presentation, SCC is found on the glans in 48% of cases, the prepuce in 21%, the glans and prepuce in 9%, the coronal sulcus in 6%, and the shaft in <2%.37
An extensive literature search was performed using the key words squamous cell carcinoma of the penis, phimosis, circumcision, chronic balanitis, cigarette smoking, genital warts and human papillomavirus (HPV) infection. All selected studies were classified according to the level of evidence (LE). The final grades of recommendation were assigned after discussion by the full panel of the International Consultation on Penile Cancer in November 2008. The factors positively associated with invasive penile cancers include the presence of phimosis (LE 3a), tobacco smoking (LE 3a-4), chewing tobacco (LE 3a), injury to the penis (LE 3a), balanitis (LE 3a), genital warts (LE 3a), and high-risk HPV infection (LE 3a-4).
Two types of squamous cell carcinoma of the palatine tonsil characterized by distinct etiology, molecular features and outcome
2008, Cancer Letters
To determine whether human papillomaviruses (HPV) positive tonsillar squamous cell carcinoma (SCC) represent a specific entity, we studied the prevalence of HPV association and of tobacco/alcohol exposure in a series of 52 cases of tonsillar SCC cases. p53, p16, and pRb levels, deregulated by viral oncoproteins were assessed. Forty patients reported tobacco/alcohol exposure, 10 reported no exposure. HPV DNA was found in 32/52 (62%) cases, (HPV16 genotype in 27). All patients with no history of tobacco-alcohol exposure presented HPV positive tumor (p = 0.0008). A strong correlation was observed between positive HPV status, decrease in pRB and increase in p16 expression level. 5 year overall survival rate was higher in HPV16 positive patients than in HPV negative (71% versus 36%; p = 0.023). HPV status remained a significant prognostic factor in multivariate analysis. Tonsillar SCC can thus be divided in HPV positive and negative subgroups with different oncogenesis and response to treatment.
Current issues in the management of advanced squamous cell carcinoma of the penis
2003, Urologic Oncology: Seminars and Original Investigations
Effective treatment of penile carcinoma incorporates three modalities: surgery, radiation and chemotherapy. Surgery alone may offer a high cure rate in early stages of the disease. In certain patients radiation therapy may be utilized to eradicate the tumor and allow organ preservation. For patients with locally advanced disease, multi-modality approaches incorporating adjuvant or neoadjuvant chemotherapy and radiation therapy need to be studied. This approach may confer a survival benefit to a group that would otherwise have a poor prognosis. Finally, in the setting of metastatic disease, less toxic and more effective combination chemotherapy are sought. Novel targeted therapies that have been successful in squamous cell carcinoma at other sites must also be studied in this disease. We believe that multi-institutional trials should be designed in order to obtain prospective benchmark data from which to make valid comparisons of outcome.

View all citing articles on Scopus

View full text

Original contributionAssociation of human papillomavirus with penile carcinoma: A study using polymerase chain reaction and in situ hybridization

Abstract

J Urol

Methods Enzymol

Heterogeneity of the human papillomavirus group

J Virol

The human papillomaviruses: An overview

Am J Med

Human papillomavirus and anogenital neoplasia: A fresh look at the association

South Med J

Human papillomavirus: The untreated male reservoir

J Urol

Penile studies and heterosexual partners

Cancer

Subclinical penile human papillomavirus infection and dysplasia in consorts of women with cervical neoplasia

Genitourin Med

Human papillomavirus: A study of male sexual partners

Med J Aust

Epidemiology of cancer of the penis: Recent results

Cancer Res

Detection of human papilloma virus paraffin-embedded tissue using the polymerase chain reaction

J Exp Med

Original contribution
Association of human papillomavirus with penile carcinoma: A study using polymerase chain reaction and in situ hybridization