HPV-related cancer prevention and treatment
Human papilloma virus (HPV) was discovered in cervical cancer
in 1983, and by 1999, was proven to cause nearly all cervical cancer.
HPV also causes genital warts.
45% of all women in the US between the ages of 20 and 24 are infected with HPV.
Two vaccines that prevent HPV infection are in use today,
and are both safe and effective at preventing cervical cancer.
(One, Gardasil, is also safe and effective at preventing genital warts.)
Testing for HPV is an effective way to prevent cervical cancer in women over 30.
In 1983, Harald zur Hausen published the paper "A papillomavirus DNA from a
cervical carcinoma and its prevalence in cancer biopsy samples from
different geographic regions" in which he described a new virus, HPV 16,
which was present in 11 of 18 german cervical cancer samples.
In 1989, the paper "Immortalization of human
foreskin keratinocytes by various human papillomavirus DNAs corresponds to
their association with cervical carcinoma"
showed that the types of HPV associated with cancer could immortalize human cells (a neccessary
part of carcinogenisis).
In 1993, the paper "Epidemiologic evidence
showing that human papillomavirus infection causes most cervical
intraepithelial neoplasia" showed that HPV accounted for most of
the risk from the classic risk factors for cervical cancer:
high number of sex partners, cigarette smoking, low age at
first intercourse, and lower socioeconomic status.
Also in 1993, the paper "The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53"
showed that HPV deactivates the anti-cancer gene P53.
In 1999, the paper "Human papillomavirus is
a necessary cause of invasive cervical cancer worldwide"
established that HPV is present in nearly all cervical cancer.
Those five papers, and the accumulated understanding we have today of
how HPV works, establish beyond a reasonable doubt that
HPV causes nearly all cervical cancer today.
As a result, Harald zur Hausen won the 2008
Nobel Prize for Medicine for his discovery.
It is estimated that
26% of American women and
20% of American men are infected with HPV.
About 7% of Americans have oral HPV infections.
The World Health Organization estimates that HPV causes 275,000 cervical cancer deaths per year worldwide.
The CDC says
HPV has been found to be associated with several types of cancer:
cervical, vulvar, vaginal, penile, anal, and
Some studies have found that HPV is also associated with breast cancer
(e.g. pubmed 12082399,
but this link is not yet well established.
can cut the risk of HPV infection in men by 30%
consistent condom use can cut the risk of HPV infection in young women by 70%,
the most effective intervention is vaccination.
Clinical trials show that vaccination against HPV effectively prevents
against the strains of HPV that cause about 70% of cervical cancer
21629249) and reduces high-grade cervical lesions (precursors to cancer)
(text, pubmed 17671238).
Consequently, HPV vaccination is now recommended by most national health organizations, including:
Vaccination campaigns have been underway since about 2007,
and efforts are underway to monitor their
safety and effectiveness:
- The HPV vaccine
impact monitoring project (HPV-IMPACT): assessing early evidence of
vaccination impact on HPV-associated cervical cancer precursor lesions (
- Monitoring of human papillomavirus vaccination (
pubmed 21062269 )
- Report of the meeting on HPV Vaccine Coverage and Impact Monitoring (
- Approaches to monitoring biological outcomes for HPV (
- Monitoring the control of human papillomavirus (HPV) infection and related diseases in Australia: towards a national HPV surveillance strategy (
- Post-licensure monitoring of HPV vaccine in the United States. (
Definitive evidence of actual cancer prevention is not expected until ten or twenty years
after the start of the public vaccination campaigns - about 2018 or 2028 -
but some health benefits will show up sooner.
Firstly, public campaigns using Gardasil already seem to be effective against genital warts:
Second, there is already a little evidence that HPV immunization campaigns are effective at reducing abnormal pap smears (a precuror to cancer):
The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme
paid text /
"of new patients attending Melbourne Sexual Health Centre... Comparing the two 12-month periods of 2007/2008 and 2010/2011, [genital warts] declined in women under 21 years from 18.6% to 1.9% and in heterosexual men under 21 years from 22.9% to 2.9%."
Impact of the human papillomavirus (HPV) vaccine on genital wart diagnoses at Auckland Sexual Health Services
"[In] clients under the age of 20 years, found genital warts in males
decreased from 11.5% in 2007 to 6.9% in 2010 while in females the rates
decreased from 13.7% to 5.1% over the same time period."
Finally, the vaccine won't do any good if people don't take it, so a number of
studies have been done on public acceptance of HPV vaccination; here is a small sampling.
Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study
- Statistical Report 2010, Victorial Cervical Cytology Registry (
"As compared with 2008, the age-specific curves for 2009 and 2010 for younger
women (aged 20 to 24 years) show a decline in high-grade detection rate for
the 20 to 24 year old age group from 19.8 in 2008 to 17.7 per 1,000 in
2010. ... It is possible that this represents an early effect of the HPV
Figure 5.2 shows the rate of histologically-confirmed highgrade cervical
abnormalities over time, by age-group. A clear
decline is evident in women under 20 years, with a rate of 15 cases per
1,000 women diagnosed in 2006 compared to
11 cases per 1,000 in 2010. This is not shown in older women,
and is suggestive of an early impact of the HPV vaccine"
- Cervical Screening in Australia 2008-2009 (
"Women aged less than 20 years,
despite having a steady rate of high-grade abnormality detection between 2.1% and 2.4% of
cytology tests between 2004 and 2008, fell to 1.8% in 2009 (Figure 3.3D). Data are needed
from 2010 to know if this is the start of a downward trend for this age group."
- Cervical Screening in Australia 2009-2010 (
) - no clear signal yet from HPV vaccination
More about the qualms some parents have about HPV vaccination
Global challenges of implementing human papillomavirus vaccines (
- National and State Vaccination Coverage Among Adolescents Aged 13 Through 17 Years --- United States, 2010 (
- Explaining variation in the uptake of HPV vaccination in England (
- HPV vaccine acceptance, utilization and expected impacts in the U.S.: Where are we now? (
- A Population-Based Evaluation of a Publicly Funded, School-Based HPV Vaccine Program in British Columbia, Canada: Parental Factors Associated with HPV Vaccine Receipt (
Challenges and Opportunities for U.S. Family Planning Clinics in Providing the HPV Vaccine (
policy paper )
Merck is currently
studying a HPV vaccine that protects against 9
strains of HPV; it might become available in 2013.
CDC recommends periodic pap smears, plus an hpv test for women over 30.
(Someday, HPV testing might suffice, at least for women over 30.)
A six-year study
of 24000 European women (BMJ 2008) concluded:
"Cervical screening strategies with HPV testing every six years is safe and
An eight-year study in
India of 130,000 women 30-59 (N Engl J Med. 2009) concluded:
"In a low-resource setting, a single
round of HPV testing was associated with a significant reduction in the
numbers of advanced cervical cancers and deaths from cervical cancer."
A study of 90,000
European women (Lancet Oncol. 2010) concluded
"HPV-based screening is more effective than cytology in preventing invasive
cervical cancer, by detecting persistent high-grade lesions earlier and
providing a longer low-risk period. However, in younger women, HPV
screening leads to over-diagnosis of regressive CIN2."
A five-year study in the Netherlands (Lancet Oncology, 2011)
"HPV DNA testing in cervical screening leads to earlier
detection of clinically relevant CIN grade 2 or worse, which when
adequately treated, improves protection against CIN grade 3 or worse and
cervical cancer. Early detection of high-grade cervical legions caused by
HPV16 was a major component of this benefit. Our results lend support to
the use of HPV DNA testing for all women aged 29 years and older."
While there are already non-HPV-specific therapies for cervical
cancer, researchers are looking for more effective HPV-specifc
therapies. So far, there are scattered reports of remission in
Phase II trials, but no Phase III trials have been carried out as
Here are some specific vaccines that have been tested:
search clinicaltrials.gov for open therapeutic HPV clinical trials.
- Pentarix: A novel, broad spectrum therapeutic HPV vaccine targeting the E7 proteins of HPV16, 18, 31, 45 and 52 that elicits potent E7-specific CD8T cell immunity and regression of large, established, E7-expressing TC-1 tumors (
- TG4001: Regression of high-grade cervical intraepithelial neoplasia
with TG4001 targeted immunotherapy. (
- TA-CIN, a vaccine incorporating a recombinant HPV fusion
protein (HPV16 L2E6E7) for the potential treatment of HPV16-associated
genital diseases. (
pubmed 20886392 )
- SGN-00101: A phase II study of Hsp-7 (SGN-00101)
in women with high-grade cervical intraepithelial neoplasia. (
- MVA E2: Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is
stimulated by therapeutic vaccination with MVA E2 recombinant vaccine. (
); MVA E2 recombinant vaccine in the treatment of human papillomavirus
infection in men presenting intraurethral flat condyloma: a phase I/II
pubmed 17263589 )
- TA-GW: Phase IIa safety and immunogenicity of a therapeutic vaccine,
TA-GW, in persons with genital warts. (
- TA-HPV: A recombinant vaccinia virus encoding human papillomavirus
types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. (
pubmed 8684105 )
-- tested in 1996
Here are a few such trials:
Here are some papers on the subject:
- Targeting HPV16 E6-p300 interaction reactivates p53 and inhibits the tumorigenicity of HPV-positive head and neck squamous cell carcinoma. (
- New Approaches to Immunotherapy for HPV Associated Cancers (
- Papillomavirus virus like particle-based therapeutic vaccine against human papillomavirus infection related diseases: immunological problems and future directions. (
- HPV and Therapeutic Vaccines: Where are We in 2010? (
- Human papillomavirus-specific immune therapy: failure and hope (
- Immunotherapy for cervical cancer: Research status and clinical
pubmed 20199126 )
Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers (
Human immunodeficiency virus and human papilloma virus - why HPV-induced lesions do not spontaneously resolve and why therapeutic vaccination can be successful (
- Search for HPV treatment vaccine heats up, researchers optimistic (
Vaccines against human papillomavirus and cervical cancer: promises and challenges. (
Copyright 2011, 2012, 2013, Dan Kegel
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