Cancer is a terrifying malady, and the threat of it has been a powerful motivation for circumcising babies, reaching its nadir in David Reuben's compendium of misinformation, Everything You Always Wanted To Know About Sex... with its "... and the remedy for penile cancer is CASTRATION. And THAT is THAT."

Who would not circumcise to prevent castration? The reality is more ambiguous.

• Penile cancer
• Prostate cancer
• Cervical cancer

• Rarity
• American Cancer Society
• Could circumcision cause penile cancer in Saudi Arabia
• or Brazil?
• Not quite cancer

J Urol. 2006 Feb;175(2):557-61

Outcome of penile cancer in circumcised men.
Seyam RM, Bissada NK, Mokhtar AA, Mourad WA, Aslam M, Elkum N, Kattan SA, Hanash KA.
Department of Urology, King Faisal Specialist Hospital and Research Center Riyadh, Saudi Arabia. rmseyam@hotmail.com

PURPOSE: We previously reported on a group of patients with post-circumcision carcinoma of the penis. We now study the long-term outcome of these patients.

MATERIALS AND METHODS: We retrospectively reviewed the available charts of 22 patients presenting between October 1979 and May 2000.

RESULTS: Of 22 patients 18 underwent ritual circumcision with extensive scar development. Median age at diagnosis was 62.4 years. The penile lesion was dorsal and proximally located in 15 patients. Median delay before diagnosis was 12 months. Clinically 14 patients had stage T1-T2 disease, with 13 having no lymph node involvement and none with distant metastasis, 8 patients had stage T3-T4 disease. A total of 15 patients were treated surgically with total penectomy (10) or conservative local excision (5), inguinal lymph node dissection (9) and subsequent penile reconstruction (3). Pathological staging in 15 patients revealed 10 patients with stage T1 and in 8 patients with lymph node dissection none had nodal metastasis. Histopathological classification was 20 squamous cell carcinoma, 1 sarcoma and 1 verrucous carcinoma. Six patients refused surgery and 1 was referred for palliation. Median followup was 14.5 months and median survival was 14.5 months. The 3-year survival was 42% for stage T1-T2 and 13% for T3-T4 (p = 0.0052). Median survival for the surgical group was 34 months whereas for nonsurgical group was 3 months (p = 0.0016). Recurrence-free survival in the surgical group was 50%.

CONCLUSIONS: Penile carcinoma in circumcised men is a distinct disease commonly following nonclassic vigorous circumcision. Delayed diagnosis and deferring surgical treatment are associated with increased mortality.

PMID: 16406995 [PubMed - in process]

Int Braz J Urol. 2011 Mar-Apr;37(2):231-43.
Epidemiological aspects of penile cancer in Rio de Janeiro: evaluation of 230 cases.
Koifman L, Vides AJ, Koifman N, Carvalho JP, Ornellas AA.

Abstract

Purpose: To determine epidemiological characteristics of penile cancer in Rio de Janeiro, its associated risk factors and clinical manifestations.

Patients and Methods: Between 2002 and 2008 we evaluated 230 patients at three public institutions, considering age, ethnicity, birthplace, marital status, educational level, religion, tobacco smoking, presence of phimosis and practice of circumcision.

Results: The ages ranged from 25 to 98 years, with an average of 58.35 years. Of the 230 patients, 167 (72.7%) were from the southeast region of Brazil (which includes Rio de Janeiro) and 45 (19.5%) were from the northeast of the country. Most patients were white (67.3%), married (58.6%), smokers (56.5%) and had not completed primary school (71.3%). The predominant religion was Catholic (74.8%). Of the 46 (20%) circumcised patients, only 1 (2.2%) had undergone neonatal circumcision. [This is meaningless without knowing what proportion of the general population was circumcised, and what proportion was circumcised neonatally.] Grade I tumors were present in 87 (37.8%) of the patients, grade II in 131 (56.9%) and grade III in 12 (5.3%). Lymphovascular embolization was observed in 63 (27.3%) and koilocytosis in 124 (53.9%) patients. Of the total, 41.3% had corpora cavernosa or corpus spongiosum infiltration, and 40 (17.4%) had urethral invasion. Prophylactic lymphadenectomy was performed on 56 (36.1%), therapeutic lymphadenectomy on 84 (54.2%) and hygienic lymphadenectomy for advanced disease on 15 (9.7%) patients. The median time between the lesion onset and clinical diagnosis was 13.2 months. The mean follow up was 28.8 months.

Conclusion: Most of our patients were born in this state and had low socioeconomic status. Most of them were white men, married, smokers, uncircumcised, of the Catholic faith and in their sixties or older. Their disease was in most cases diagnosed only in the advanced stages.

[The rate of circumcision in Brazil is known to be low, but reliable data is hard to come by. (Wikipedia - not known as an anti-circumcision site - says 7.4%, citing a study of the partners of 66 women! It also says 13% in Rio de Janiero, but that city is not mentioned in its reference.) If it is lower than 20%, as it almost certainly is, then circumcision is not protective against penile cancer, and may be a risk factor for it.]

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East Afr Med J. 2000 Oct;77(10):526-30.

Cancer of the penis at Kenyatta National Hospital.

Abstract

OBJECTIVES:
To determine how common cancer of penis is in this locality compared to all other malignant tumours and urological malignancies, and to determine and comment on the various methods of treatment available at KNH.

DESIGN:
A retrospective case study.

SETTING:
Kenyatta National Referral Hospital, Nairobi.

SUBJECTS:
All patients with histologically confirmed cancer of penis at the Kenyatta National hospital between January 1970 and December 1999.

RESULTS:
There were 55 patients with penile cancer representing 0.1% of all malignancies during the study period. [That is, one cancer in 1000 is penile - not all people get cancer, so a man's risk of penile cancer is well under 1 in 1000.] The mean age was 47.9 years with a peak incidence between 40-61 year age groups. Penile cancer was the most rare urological tumour representing 5.1%. The most common was prostate cancer (56.0%), followed by bladder cancer (25.0%), kidney cancer (7.9%), and testicular cancer (6.1%). Thirty eight patients (69.1%) presented with advanced disease, Jacksons stages III and IV. The majority (96.4%) of the patients had glandular and preputial involvement. Histologically, 56.4% had well differentiated squamous cell carcinoma, (23.6%) had moderately differentiated and (20.0%) had undifferentiated carcinoma. Forty patients (72.7%) were circumcised, nine patients (16.4%) were circumcised as adolescents and three patients (5.5%) circumcised as adults. [Implying 28 patients (50.9%) were circumcised as infants, giving the lie to the claim that infant circumcision is better at preventing penile cancer than later circumcision.] Twenty five patients had partial penectomy with radiotherapy and or chemotherapy. Eight patients had total penectomy and radiotherapy while four patients had local excision and radiotherapy. Eleven other patients had radiotherapy either alone or combined with chemotherapy. Two patients had circumcision only and inguinal lymphadenectomy was effected on five patients after penectomy and radiotherapy.

CONCLUSION:
Penile cancer is rare and the least common urological malignancy in this locality. It occurs in younger men with a mean age of 47.9 years, and presents as advanced Jackson's stages III and IV disease. The majority of patients had penectomy and local excision followed by radiotherapy.

Int J Cancer. 2011 May 26. doi: 10.1002/ijc.26196. [Epub ahead of print]

Male circumcision is associated with a lower prevalence of human papillomavirus-associated penile lesions among Kenyan men.

Backes DM, Bleeker MC, Meijer CJ, Hudgens MG, Agot K, Bailey RC, Ndinya-Achola JO, Hayombe J, Hogewoning CJ, Moses S, Snijders PJ, Smith JS.

Abstract

Human papillomavirus (HPV)-associated penile lesions in men may increase the risk of HPV transmission to their female partners. Risk factor data on HPV-associated penile lesions are needed from regions with a high burden of cervical cancer. Visual inspection of the penis was conducted using a colposcope at the 24-month visit among participants in a randomized controlled trial of male circumcision in Kenya, from May 2006 to October 2007. All photos were read independently by two observers for quality control. Penile exfoliated cells sampled from the glans/coronal sulcus and the shaft were tested for HPV DNA using GP5+/6+ PCR and for HPV16, 18 and 31 viral loads using a real time PCR assay. Of 275 men, 151 were circumcised and 124 uncircumcised. The median age was 22 years. Circumcised men had a lower prevalence of flat penile lesions (0.7%) versus uncircumcised (26.0%); adjusted odds ratio (OR) = 0.02; 95% confidence interval (CI) = 0.003-0.1. [And the p?] Compared to men who were HPV negative, men who were HPV DNA positive (OR = 6.5; 95% CI = 2.4-17.5) or who had high HPV16/18/31 viral load (OR = 5.2; 95% CI = 1.1-24.4) had higher odds of flat penile lesions. Among men with flat penile lesions, HPV56 (29.0%) and 16 (25.8%) were the most common types within single or multiple infections. Flat penile lesions are much more frequent in uncircumcised men and associated with higher prevalence of HPV and higher viral loads. This study suggests [weasel-word] that circumcision reduces the prevalence of HPV-associated flat lesions and may ultimately reduce male-to-female HPV transmission. [This study massages and mines the data, which only indicate that circumcised men have raised lesions, intact men flat ones - perhaps pressure from the foreskin flattens the leisions?]

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• Faulty basis of the claim
• Contrary findings
• More recent claims

These more recent studies demonstrate that the orginal low incidence of cervical cancer in Israeli Jewish women is genetic. The first shows that women have as many pre-cancerous lesions as other women (suggesting the same exposure to HPV) but they tend not to progress to cancer because of a certain allele (variant) in the p53 gene (whose normal function is to control cell proliferation). In Moroccan Jewish women, who have a high incidence of cervical cancer, the cancer-permitting allele of p53 is more common. These are good studies demonstrating the interaction between genetics and environment.

1. Premalignant lesions of the uterine cervix in a large cohort of Israeli Jewish women.

Sadan O, Schejter E, Ginath S, Bachar R, Boaz M, Menczer J, Glezerman M.
Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Sacker Faculty of Medicine, Tel Aviv University, Holon 58100, Tel Aviv, Israel.

Arch Gynecol Obstet. 2004 Mar;269(3):188-91. Epub 2003 Oct 24.

Israeli Jewish women are at low risk for cancer of the uterine cervix. In view of absent screening programs in Israel, there are only scarce data available with regard to results of PAP smears. The aim of this study was to assess the incidence of premalignant cervical lesions in the largest sample of PAP smears reported so far from Israel. We retrospectively analyzed the results of 297,849 PAP smears, which had been examined in a single laboratory, during 9 years (1991-1999). The incidence of low- and high-grade squamous intraepithelial was 0.69% and 0.29%, respectively. Our data indicate similar incidence rates for premalignant lesions in Jewish Israeli women as observed in Western countries, but no increase during the study period. In spite of relatively high incidence rates for premalignant lesions of the uterine cervix, the incidence rate for invasive cervical cancer remains conspicuously low. For unknown reason the conversion rate from premalignant cervical lesions to invasive cancer is lower in Israeli Jewish women than in European and North American women. We discuss possible reasons for this phenomenon and suggest that at this time mass screening for cervical cancer in Israel may probably not be justified.

PMID: 14576953 [PubMed - in process]

2. Codon 72 polymorphism of p53 in Israeli Jewish cervical cancer patients and healthy women.

Arbel-Alon S, Menczer J, Feldman N, Glezerman M, Yeremin L, Friedman E.
Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel.

Int J Gynecol Cancer. 2002 Nov-Dec;12(6):741-4.

Recently it has been found that the presence of homozygous arginine polymorphism at codon 72 of p53, represents a significant risk factor in the development of HPV-associated cervical cancer. The incidence of cervical carcinoma is persistently very low in Israeli Jewish women for unknown reasons. The incidence among those of North African origin is relatively higher. The aim of the present study was to assess the frequency distribution of the p53 homozygous arginine polymorphism in cervical cancer patients and in a population sample of healthy Israeli Jewish women in order to determine whether the incidence pattern among them is genetically based. The cases consisted of 23 Israeli Jewish patients with histologically confirmed squamous cell carcinoma of the cervix. A group of 162 randomly chosen Israeli Jewish healthy participants, considered to represent the general population, comprised the controls. The germline p53 polymorphism at codon 72 was determined by PCR in DNA obtained from a blood sample taken from each subject.

Homozygous arginine was found in 34.8% of cases and in only 14.8% of controls. This difference was statistically significant (P = 0.01). The frequency of homozygous arginine polymorphism in controls was lower than in any other population hitherto reported. It was significantly more common among those of North African than among those of other origin (30.3% vs. 10.8%; P < 0.01). It may be assumed that the low incidence of cervical cancer in Israeli Jewish women and the differences between the ethnic groups may be related to the frequency pattern of the homozygous arginine p53 polymorphism

PMID: 12445252 [PubMed - indexed for MEDLINE]

Humans have two copies of each gene, and a polymorphism means that one gene is slightly different to the other. The open reading frame is a special segment of a gene which acts as an instruction for the cell to synthesize a protein.

Proteins are made up of amino acids (there are 20 different amino acids) which link together to form a chain, which can then tie in knots to form three dimensional biomolecules. Proteins are the building blocks of life, and include enzymes, contractile fibres (in cells, especially muscle), and structural fibres. Proteins can also be combined with other molecules such as fats and sugars.

A homozygous arginine polymorphism at codon 72 means that the two alleles (two copies of DNA coding for the same protein) are homozygous, or code for the same amino acid (arginine) at position number 72 along the amino acid of the p53 protein.

Mutations in the gene coding for another protein (BRCA) have been linked to breast cancer, and Menczer showed that this may also be linked to cervical cancer.

Genetic factors are very important for human susceptibility to many infectious diseases, including HIV.

The case is summarised in:

The low incidence of cervical cancer in Jewish women: has the puzzle finally been solved?

Menczer J.
Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel. joseph12@internet-zahav.net

Isr Med Assoc J. 2003 Feb;5(2):120-3.

PMID: 12674663 [PubMed - indexed for MEDLINE]

Effect of Male Circumcision on the Prevalence of High-Risk Human Papillomavirus in Young Men: Results of a Randomized Controlled Trial Conducted in Orange Farm, South Africa

Bertran Auvert, Joelle Sobngwi-Tambekou, Ewalde Cutler, Marthi Nieuwoudt, Pascale Lissouba, Adrian Puren and Dirk Taljaard

Background. A causal association links high-risk human papillomavirus (HR-HPV) and cervical cancer, which is a major public health problem. The objective of the present study was to investigate the association between male circumcision (MC) and the prevalence of HR-HPV among young men.

Methods. We used data from a MC trial conducted in Orange Farm, South Africa, among men aged 18–24 years. Urethral swab samples were collected during a period of 262 consecutive days from participants in the intervention (circumcised) and control (uncircumcised) groups who were reporting for a scheduled follow-up visit.
[Aguilar et al. found that urethral swab samples were less than half as likely to give a positive result as penile shaft samples. Neilson et al. found that the penile shafts of circumcised men were only very marginlly less likely to carry HPV than those of intact men. In other words, the finding that circumcised men were less likely to carry HPV was an artifact of the site Auvert et al. chose to sample.]
Swab samples were analyzed using polymerase chain reaction. HR-HPV prevalence rate ratios (PRRs) were assessed using univariate and multivariate log Poisson regression.

Results. In an intention-to-treat analysis, the prevalences of HR-HPV among the intervention and control groups were 14.8% (94/637) and 22.3% (140/627), respectively, with a PRR of 0.66 (0.51– 0.86) (P
.002). Controlling for propensity score and confounders (ethnic group, age, education, sexual behavior [including condom use], marital status, and human immunodeficiency virus status) had no effect on the results. [What? Circumcision made a difference but condom use didn't? How is that possible? Something is very wrong here.]

Conclusions. This is the first randomized controlled trial to show a reduction in the prevalence of urethral HR-HPV infection after MC. This finding explains why women with circumcised partners are at a lower risk of cervical cancer than other women. [And Auvert's reference for this claim is an article by arch-circumcisionist Brian Morris in a molecular medicine journal (his official specialty) extolling circumcision for every purpose imaginable. Morris's references for the claim is the Castellsagué study above and a study by Halperin, Bailey, et al. of the rates in different developing countries, that does not actually establish correlation between individuals, only populations.]

Associations between Male Anogenital Human Papillomavirus Infection and Circumcision by Anatomic Site Sampled and Lifetime Number of Female Sex Partners

Carrie M. Nielson, Melody K. Schiaffino, Eileen F. Dunne, Jason L. Salemi, and Anna R. Giuliano

Background. Male circumcision may lower men’s risk of human papillomavirus (HPV) infection and reduce transmission to sex partners. Reported associations between circumcision and HPV infection in men have been inconsistent.

Methods. Four hundred sixty-three men in 2 US cities were tested at 6 anogenital sites and in semen for 37 types of HPV. Men were eligible if they reported sex with a woman within the past year, no history of genital warts or penile or anal cancer, and no current diagnosis of a sexually transmitted infection. Participants completed a self administered questionnaire. Circumcision status was assessed by the study clinician. Logistic regression was used to examine associations between circumcision and HPV detection at each site and in semen, with adjustment for potential confounders.

Results. Seventy-four men (16.0%) were uncircumcised. Adjusted odds ratios (AORs) for any HPV genotype and circumcision were 0.53 (95% confidence interval [CI], 0.28–0.99) for any anatomic site/specimen, 0.17 (95% CI, 0.05–0.56) for the urethra, 0.44 (95% CI, 0.23–0.82) for the glans/corona, and 0.53 (95% CI, 0.28–0.99) for the penile shaft. [A 95% CI that crosses 1.0 means there is no statistical significance to a result.] AORs were <1.0 but not statistically significant for the scrotum, semen, anal canal, and perianal area.

Conclusions. Circumcision may [or may not] be protective against HPV infection of the urethra, glans/corona, and penile shaft.

Circumcision and sexual behavior: Factors independently associated with human papillomavirus detection among men in the HIM study

Anna R. Giuliano, Eduardo Lazcano, Luisa Lina Villa, Roberto Flores, Jorge Salmeron, Ji-Hyun Lee, Mary Papenfuss, Martha Abrahamsen, Maria Luiza Baggio, Roberto Silva, Manuel Quiterio

This article was presented in part: 24th International Papillomavirus Conference and Clinical Workshop, November 2007, Beijing, China Abstract # 8B-04.

Funded by: National Institutes of Health (National Cancer Institute); Grant Number: RO1CA098803

Abstract
There is growing interest in understanding human papillomavirus (HPV) infection and related disease among men. To date there have been numerous studies reporting HPV DNA prevalence among men from several different countries, however, few have incorporated multivariable analyses to determine factors independently associated with male HPV detection. The purpose of this study was to assess the factors independently associated with HPV detection in men ages 18-70 years residing in Brazil (n = 343), Mexico (n = 312), and the United States (US) (n = 333). In samples combined from the coronal sulcus, glans penis, shaft, and scrotum, we evaluated factors associated with any, oncogenic, and nononcogenic HPV infections. In multivariable analyses, detection of any HPV infection was significantly associated with reported race of Asian/Pacific Islander, lifetime and recent number of sexual partners, and having sex in the past 3 months. Oncogenic HPV detection was independently associated with lifetime and recent number of sexual partners, and having sex in the past 3 months. NonOncogenic HPV infection was independently associated with lifetime number of sexual partners. Circumcision, assessed by clinical examination, was associated with reduced risk of HPV detection across all categories of HPV evaluated. [This is absurd: there would have been virtually no circumcised men in Mexico or Brazil, and few intact men in the US, so it is a cross-country comparison. Any of a number of demographic factors could be associated with circumcision status, confounding any association with HPV.] HPV detection in men in the current study was strongly related to sexual behavior and circumcision status. Interventions such as circumcision may provide a low-cost method to reduce HPV infection. [And therefore Carthage must be destroyed.]

© 2008 Wiley-Liss, Inc. Received: 19 June 2008; Accepted: 9 September 2008

BMC Infectious Diseases 2013, 13:18 doi:10.1186/1471-2334-13-18 Published: 17 January 2013

Male circumcision and prevalence of genital human papillomavirus infection in Men: a multinational study

Ginesa Albero, Luisa L Villa, Eduardo Lazcano-Ponce, William Fulp, Mary R Papenfuss, Alan G Nyitray, Beibei Lu, Xavier Castellsagué, Martha Abrahamsen, Danélle Smith, F Xavier Bosch, Jorge Salmerón, Manuel Quiterio and Anna R Giuliano

Abstract (provisional)
Background
Accumulated evidence from epidemiological studies and more recently from randomized controlled trials suggests that male circumcision (MC) may substantially protect against genital HPV infection in men. The purpose of this study was to assess the association between MC and genital HPV infection in men in a large multinational study.

Methods
A total of 4072 healthy men ages 18-70 years were enrolled in a study conducted in Brazil, Mexico, and the United States. [So as above, most of the intact men were from Brazil and Mexico, almost all the circumcised men from the USA, with many demographic confounders.] Enrollment samples combining exfoliated cells from the coronal sulcus, glans penis, shaft, and scrotum were analyzed for the presence and genotyping of HPV DNA by PCR and linear array methods. Prevalence ratios (PR) were used to estimate associations between MC and HPV detection adjusting for potential confounders.

Results
MC was not associated with overall prevalence of any HPV, oncogenic HPV types or unclassified HPV types. However, MC was negatively associated with non-oncogenic HPV infections (PR 0.85, 95% confident interval: 0.76-0.95), in particular for HPV types 11, 40, 61, 71, and 81. [This is data-mining.] HPV 16, 51, 62, and 84 were the most frequently identified genotypes regardless of MC status.

Conclusions
This study shows no overall association between MC and genital HPV infections in men, except for certain non-oncogenic HPV types for which a weak association was found. However, the lack of association with MC might be due to the lack of anatomic site specific HPV data, for example the glans penis, the area expected to be most likely protected by MC. [In other words, they're desperately looking for some way to save circumcision.]

Journal of Infectious Diseases, Volume203, Issue1, p. 58-65

External Genital Human Papillomavirus Prevalence and Associated Factors Among Heterosexual Men on 5 Continents

Eftyhia Vardas, Anna R. Giuliano, Stephen Goldstone, Joel M. Palefsky, Edson D. Moreira Jr., Mary E. Penny, Carlos Aranda, Heiko Jessen, Harald Moi, Daron G. Ferris, Kai-Li Liaw, J. Brooke Marshall, Scott Vuocolo, Eliav Barr, Richard M. Haupt, Elizabeth I.O. Garner and Dalya Guris

Abstract

Background. We examined the baseline prevalence of penile, scrotal, and perineal/perianal human papillomavirus (HPV) in heterosexual men (HM). We also evaluated baseline characteristics of HM to assess factors associated with prevalent HPV detection.

Methods. We tested serum samples from 3463 HM aged 16–24 years with 1–5 lifetime female sexual partners for antibodies to HPV 6, 11, 16, and 18. We collected baseline swab specimens for the detection of DNA of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 from 3 areas: penile, scrotal, and perineal/perianal. Risk factors for prevalent HPV DNA detection were evaluated.

Results. The prevalence of any tested HPV type was 18.7% at the penis, 13.1% at the scrotum, 7.9% at the perineal/perianal region, and 21.0% at any site. Having >3 lifetime female sexual partners had the greatest impact on HPV prevalence: odds ratio (OR) 3.2 (95% confidence interval (CI) 2.1–4.9) for HPV 6, 11, 16, and 18; and OR 4.5 (95% CI 3.3–6.1) for all HPV types tested. HPV DNA detection was highest in Africa. Neither condom usage nor circumcision was associated with HPV DNA prevalence.

Conclusion. Genital-HPV DNA detection is common in young, sexually active HM. We found HPV to be most prevalent in African men and least prevalent in men from the Asia-Pacific region. Increased numbers of sexual partners was an important risk factor for HPV DNA prevalence.

The Lancet, Early Online Publication, 7 January 2011

Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda

Prof Maria J Wawer MD, Dr Aaron AR Tobian MD, Godfrey Kigozi MBChB, Xiangrong Kong PhD, Patti E Gravitt PhD, David Serwadda, Fred Nalugoda MHS, Frederick Makumbi PhD, Victor Ssempiija ScM, Nelson Sewankambo MMed, Stephen Watya MMed, Kevin P Eaton BS, Amy E. Oliver BA, Michael Z Chen MSc, Steven J Reynolds MD, Prof Thomas C Quinn MD, Prof Ronald H Gray MD

Summary

Background

Methods
... men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878.

Findings
... At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60—0·85, p=0·001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63—0·93, p=0·008). [A difference of 6.2 infections per hundred person-years - implying 16 circumcisions to prevent one infection per year.]

Interpretation
Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. [And therefore Carthage must be destroyed.] However, protection is only partial; the promotion of safe sex practices is also important.

Funding
The Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.

Cancer Epidemiology, Biomarkers and Prevention July 2005 14; 1710

Determinants of Prevalence, Acquisition, and Persistence of Human Papillomavirus in Healthy Mexican Military Men

Martín Lajous, Nancy Mueller,Aurelio Cruz-Valdéz, Luis Victor Aguilar, Silvia Franceschi, Mauricio Hernández-Ávila and Eduardo Lazcano-Ponce

Abstract
Background: Human papillomavirus (HPV) infection is sexually transmitted, but the nature of the infection in males is poorly understood. We sought to identify determinants of HPV infection, acquisition, and persistence in 1,030 healthy military men in Mexico.

Methods: From July 2000 to July 2003, trained interviewers administered a questionnaire, conducted a genital examination, and collected samples. The presence of multiple HPV types in genital cells from the urethra, urethral meatus, scrotum, penile shaft, and coronal sulcus was evaluated. At baseline 1,030 participants and after 1-year follow-up 336 individuals were sampled using a highly sensitive DNA reverse blot strip assay.

Results: HPV prevalence was 44.6%; infection with high-risk types was observed in 34.8% participants and 51.1% were multiply infected. After 1-year follow-up, 165 men remained free of HPV, 68 cleared their infection, 45 acquired one, and 37 remained infected with the same HPV type. The period prevalence was 50.9%, the incidence rate was 17.9/1,000 men-months [95% confidence interval (95% CI), 13.0-23.9], clearance was 54%, and persistence was 29.4%. At baseline, the number of partners before age 20 years, a history of a sexually transmitted disease, and the presence of condilomas significantly increased the association with HPV infection. Having anal intercourse with males was associated with the risk of acquiring a HPV infection (odds ratio, 5.2; 95% CI, 1.2-23). The odds ratio for persistent infection was 0.10 (95% CI, 0-0.87) in men who reported being circumcised compared with those who did not.

Conclusions: High-risk sexual behavior increases the risk of HPV infection in males, whereas circumcision may lower the risk of persistence.

[Or it may not.]

Sexually Transmitted Infections 2006;82:31-33; doi:10.1136/sti.2005.015131 Copyright © 2006 by the BMJ Publishing Group Ltd.

Human papillomavirus in men: comparison of different genital sites

L V Aguilar, E Lazcano-Ponce, S Vaccarella, A Cruz, P Hernández, J S Smith, N Muñoz, J R Kornegay, M Hernández-Avila, S Franceschi

Objective: To elucidate which anatomical sites need to be sampled to detect human papillomavirus (HPV) infection in the lower male genital tract.

Method: In an HPV survey of Mexican soldiers (median age 24 years; range 16–50 years), a cell sample from 2 cm deep into the distal urethra (group 1; n = 168 men), or 0.5 cm deep into the meatus urethralis (group 2; n = 414 men) was collected, along with a sample from the external genitalia. The different samples were tested for 27 HPV types using a polymerase chain reaction based strip assay.

Results: HPV DNA was detected more frequently in external genitalia samples (46.4%) than in the urethra (20.8%) or meatus samples (12.1%). Lack of samples from the urethra or meatus would have led to 5.1% and 1.5% false HPV negative results, respectively. The most frequently detected high risk HPV types (HPV 59, 52, 51, and 16) were similar in different sites, whereas low risk types were found rarely in urethra samples.

Conclusions: The addition of cell samples from the meatus to those from external genitalia contributed negligibly to the evaluation of the prevalence of HPV in men. HPV detection was slightly improved by the addition of urethra samples, but the gain may not justify the discomfort of the procedure in large epidemiological studies.

Human papillomavirus and circumcision: A meta-analysis

Robert S. Van Howe
Department of Pediatrics, Michigan State University College of Human Medicine, 1414 W. Fair Avenue, Suite 226, Marquette, MI 49855, USA Accepted 8 August 2006

Summary

Background: Determine the relationship of circumcision status to the risk for genital infection with human papillomavirus (HPV).

Methods: A MEDLINE search and a review of references in published articles were used to identify publications from peer-reviewed journals in Index Medicus with data on circumcision status in patients with and without HPV infections. Inclusion criteria included diagnosis by culture, biopsy, or PCR, determination of circumcision status by physical examination, and multiple site sampling including the shaft of the penis. A meta-analysis was performed with sensitivity analyses.

Results: Sixteen articles contained data on circumcision status in patients with and without HPV infections. Eight studies used accurate diagnostic methods. Only three articles satisfied the strict inclusion criteria. There was no significant association between circumcision status and HPV infection (random-effects model summary effect OR Z 1.20, 95%CI Z 0.80–1.79) in these three studies. If the eight studies using accurate diagnostic methods are adjusted for the method of determining circumcision status and failure to sample the penile shaft using meta-regression the summary effects odds ratio is 1.25 (95%CI Z0.95–1.67).

Conclusions: The medical literature does not support the claim that circumcision reduces the risk for genital HPV infection. To correctly assess the risk of HPV infection in circumcised males, the penile shaft needs to be sampled for HPV infection.

Male Circumcision and Genital Human Papillomavirus: A Systematic Review and Meta-Analysis Abstract HPV is the leading cause of invasive cervical cancer, and some evidence suggests that male circumcision (MC) may protect against this infection and related disease in both men and women. The authors undertook the current study to assess the association between MC and genital HPV infection indicators, including genital warts. They conducted a systematic search of Medline to identify all relevant studies from February 1971 to August 2010. Effect estimates were included in random effects models. The meta-analysis included 21 studies with 8,046 circumcised and 6,336 uncircumcised men. “MC was associated with a statistically significant reduced odds of genital HPV prevalence (odds ratio=0.57, 95 percent confidence interval: 0.42-0.77),” the authors found. This association was seen as well for genital high-risk HPV prevalence in two randomized controlled trials (OR=0.67, 95 percent CI: 0.54-0.82). The team found no associations between MC and genital HPV acquisition of new infections, genital HPV clearance or genital warts. “This meta-analysis shows a robust inverse association between MC and genital HPV prevalence in men,” the authors concluded. “However, more studies are needed to adequately assess the effect of MC on the acquisition and clearance of HPV infections. MC could be considered as an additional one-time preventative intervention likely to reduce the burden of HPV-related diseases both in men and women, particularly among those countries in which HPV vaccination programs and cervical screening are not available.” [Both cervical screening and HPV vaccination are known to be highly effective against cervical cancer. Why not just make them available?] Source http://www.stdjournal.com Date of Publication 02//2012 Author Ginesa Albero; Xavier Castellsagué; Anna R. Giuliano; Francesc Xavier Bosch

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Royal College of Nursing
Human papilloma virus (HPV) and cervical cancer — the facts

... Genital HPV infection is very common and all sexually active women are at risk. Indeed, HPV is so common that it can almost be considered a normal consequence of having sex. Estimates suggest that between 50% and 79% of all women who have had sexual intercourse have a lifetime risk of becoming infected with one or more of the sexually transmitted HPV types (Koutsky, 1997). Often the infection is transient and it is only when it becomes persistent, and in a small minority of women, that this may lead to CIN.

... The great majority of genital HPV infections never cause any overt symptoms and are spontaneously cleared by the immune system in a matter of months.

... There is also evidence to suggest that high risk genital HPV has been detected in nongenital areas such as the mouth, oropharynx (back of the throat) and conjunctiva (the thin transparent tissue that covers the outer surface of the eye) (Cason, 1996). It would therefore seem that HPV can be transferred during oral sex and may also be transferred via the hands, but at this moment this remains unproven.

...

Treatment and prevention of HPV
Condoms offer a degree of protection against the initial transmission of HPV infections. However, as HPV has a field effect and is present over all the genitalia, this protection is not comprehensive or complete. [And the same will be true of circumcision.]

There is currently no medical treatment for HPV, but as most HPV infections are cleared rapidly by the immune system, in most cases it’s unnecessary to treat a virus which may indeed cause no problems.

Cogito's blog
May 1, 2010

Data mining in circumcision-HPV study

Just the abstract alone raises a few red flags.

1. "There were no differences in HPV acquisition by circumcision status". So being circumcised doesn't change your risk of infection.
2. The statistic compared between the groups was the median duration, not the mean. Now it's possible that this branch of medical science has different standard tests, but in my experience the tests for statistical difference between groups always depends on the mean. Unless this type of research typically uses medians, the fact that the mean was not used raises the possibility that the desired result was not achieved when the mean was used.
3. The P value was 0.04. Even putting my general misgivings about statistical hypothesis testing aside, this result is only statistically significant at the .05 level, not the stricter .01 level usually used for work with medical implications.

But the problems get worse once you look at the actual paper (you'll probably need a university subscription to access the full text):

Read that again. If you didn't get it, I'll try to make it clear: If you consider only HPV on the penile shaft, only HPV on the scrotum, OR HPV across ALL GENITAL SITES, the duration of infection does not depend on circumcision status. It is only if you consider the glans alone that a longer infection duration is found (and the fact that the 95% confidence intervals overlapped just adds to the ridiculousness). One more time: When all genital sites are considered, the duration of infection does not depend on circumcision status. So being circumcised does not decrease your overall chance of infection, nor does it decrease the duration of an HPV infection at an arbitrary site. But wait, weren't we told differently in the abstract?

This is straight up intellectual dishonesty, and smacks of fitting the data to a pre-determined conclusion. The abstract claims the research to be a study about "the relationship between circumcision and the acquisition and clearance of human papillomavirus (HPV) infection" with no specification of where the HPV is located, and indeed HPV incidence and clearance was studied across all locations, and yet the only clearance-related result mentioned in the abstract pertains to a subset of the data, the glans/coronal sulcus data. If they really wanted to report the truth about the relationship, isn't the most important result the fact that, when all sites are considered, circumcision showed no effect on either infection or clearance?

Tuesday, May 17, 2011
Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Moderated Poster at the AUA conference, 2011
Michael Ladurner Rennau, Alexander Buttazoni, Renate Pichler, Barbara Schlenk, Gerald Klinglmair, Elisabeth Richter, Helga Fritsch, Bettina Zelger, Josef Oswald, Innsbruck, Austria

INTRODUCTION AND OBJECTIVES:
It has been well established that human papillomaviruses (HPVs) are the main risk factor for cervical carcinoma in 70 out of 100 cases. We investigated in a prospective study the epidemiology of HPV and its colonization of the male genital tract and in particular the inner layer of the foreskin. METHODS: We examined anonymized foreskins of unselected 133 males aged between 7 months and 82 years without clinical HPV associated warts, who underwent radical circumcision. Indication for circumcision was phimosis.

[No clue what caused the phimosis, but not one of these men previously had normal intact genitalia. Since none had warts, they were not even a random sample of men with HPV. It is not possible to diagnose phimosis in a baby at seven months.]

The presence of viral (HPV) nucleic acid (DNA) sequences in tissues was demonstrated via in-situ hybridization (ISH) by using labelled DNA probes. DNA extraction of 40 foreskin tissue sections was done to explore viral nucleic acid of HPV by Real-Time RT-PCR. PCR primers were used to detect HPV-DNA of low risk types (6, 11) as well as of high risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 66). These findings were correlated with in-situ hybridization data of the same tissue samples.

RESULTS:
We found a prevalence of low-risk HPV genotypes in foreskins of 18.8 %, whereas the prevalence of high-risk HPV genotypes was 9.77 %. Gene expression of both high- and low-risk HPV genotypes of the same tissue samples correlated significantly with in-situ hybridisation data.

CONCLUSIONS:
Our study revealed the occurrence of subclinical genital low and high risk HPV infections in boys and men which could be a reservoir for HPV- associated diseases. Since it is proven that viral transfer results from sexual contact it is advisable to vaccinate not only girls but also boys before adolescence.

Sexually Transmitted Diseases: February 2012 - Volume 39 - Issue 2 - p 104-113 doi: 10.1097/OLQ.0b013e3182387abd

Male Circumcision and Genital Human Papillomavirus: A Systematic Review and Meta-Analysis

Albero, G, Castellsagué, Xavier, Giuliano, Anna R., Bosch, Francesc Xavier

Background: Human papillomavirus (HPV) infection is the principal cause of invasive cervical cancer. There is some evidence that male circumcision (MC) may protect against HPV infection and related disease in both men and women. The purpose of this study was to conduct a systematic review of the literature to assess the association between MC and genital HPV infection indicators including genital warts.

Methods: A systematic search of Medline was conducted to identify all relevant studies from February 1971 to August 2010. Effect estimates were included in random effects models.

Results: A total of 21 studies with 8046 circumcised and 6336 uncircumcised men were included in the meta-analysis. MC was associated with a statistically significant reduced odds of genital HPV prevalence (odds ratio = 0.57, 95% confidence interval: 0.42–0.77). This association was also observed for genital high-risk HPV prevalence in 2 randomized controlled trials (odds ratio = 0.67, 95% confidence interval: 0.54–0.82). No associations were found between MC and genital HPV acquisition of new infections, genital HPV clearance, or genital warts.

Conclusions: This meta-analysis shows a robust inverse association between MC and genital HPV prevalence in men. However, more studies are needed to adequately assess the effect of MC on the acquisition and clearance of HPV infections. MC could be considered as an additional one-time preventative intervention likely to reduce the burden of HPV-related diseases both in men and women, particularly among those countries in which HPV vaccination programs and cervical screening are not available.