By Sin Hang Lee, M.D. Pathologist, Milford, Connecticut
Before the DC Department of Health Budget Committee meeting on May 5, 2011
Summary of testimony:
I am a medical doctor practicing hospital pathology for more than 50 years. My residency included training in the1960’s in the laboratory created by Dr. George Papanicolaou in New York Hospital. Using Pap smear to detect precancerous changes for early treatment in the U.S. has reduced the incidence of cervical cancer from 44 in 100,000 women in 1947 to about 5 in 100,000. Now, cervical cancer is a rare disease in the U.S. most among women who have no regular gynecologic health care, especially among new immigrants and the underprivileged. The average cervical cancer patient is about 54 years old.
I have also introduced a reliable HPV test to further improve the accuracy of Pap smear screening because now we know that HPV infection is a necessary, but not a sufficient cause for cervical cancer.
Mass vaccination of young women for cervical cancer prevention is not cost-effective because all vaccinated women still need post-vaccination Pap cytology screening for possible precancer development since not all cancer-causing HPV genotypes are targeted for protection by Gardasil. Gardasil has not been proven to be an effective vaccine in reducing cervical cancer incidence in clinical trials. The immunity generated by Gardasil vaccination in protection against HPV infection lasts about 4 years. A vaccinated 6th grade student would lose her immunity against HPV infection at 10th grade. The safety and efficacy of the HPV vaccine have not been tested on young girls below age 15.
Because of the nature of the HPV vaccines, Gardasil is associated with high frequencies of allergic/anaphylactic reactions. In fact, it is estimated the rate of anaphylaxis in young women after Gardasil vaccination was 5 to 20 times higher than that identified in comparable school-based vaccination programs. Some of the reactions may be serious, including permanent disability or possible death.
The benefit of mass HPV vaccination for cervical cancer prevention does not outweigh its risk. Supportive evidence is presented as follows.
(1) Cervical cancer is very preventable by Papanicolaou (Pap) smear screening
Cervix cancer is rare in this country today because most women get regular Pap tests – American Cancer Society .
Testimony on Cervical Cancer by Nancy C. Lee, M.D., the then Associate Director for Science, National Center for Chronic Disease and Health Promotion, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services before the House Committee on Commerce, Subcommittee on Health and Environment
March 16, 1999, contains the following passages :
“The main purpose of cervical cancer screening is to find precancerous lesions, treat them, and cure them, so that these women do not go on to be diagnosed with cervical cancer.”
“Cervical cancer occurs at an average age of 54; however, cervical intraepithelial neoplasia (or CIN), the precursor lesion to cervical cancer, most often occurs in much younger women. For a woman with CIN, her likelihood of survival is almost 100 percent with timely and appropriate treatment. The fact that CIN occurs at a younger age tells us that it usually takes a substantial amount of time for cervical cancer to develop.”
In 1947, the incidence of cervical cancer in the U.S. was 44 per 100,000 women, as high as in many underdeveloped countries today. Pap smear screening has reduced the incidence of cervical cancer in the U.S. to the lowest in the world. According to the CDC/NCI Cancer Progress Review dated October 16, 2002, the mortality of cervical cancer continued to decline from 1969 to 1999 for all age groups. The age-adjusted death rate per 100,000 standard population was 2.8 for cervical cancer, compared with 56.5 for lung cancer, 27.1 for breast cancer and 20.9 for colorectal cancer in year 2000 .
In the U.S., immigrant and underprivileged women who face a multitude of barriers to Pap screening and cervical cancer treatment are the major victims of cervical cancer . It is safe to say that the mainstream American women under regular care of their gynecologists do not die of cervical cancer.
(2) HPV testing increases the power to screen out women with high-risk HPV persistent infection
The current etiologic model for the development of invasive cervical cancer highlights infection with high-risk HPV types as a necessary, but not sufficient, cause of cervical cancer. This model also incorporates the role of co-factors, such as smoking, nutritional deficiencies, oral contraceptive (OC) use, and parity status in the development of cancer . A schematic diagram summarizes the three conceptual stages of cervical carcinogenesis after HPV infection is initiated. The precancerous cell changes, including the cervical intraepithelial neoplasia (CIN) lesions, are mostly self-reversible . In 93% of initially infected women the same viral type could not be detected four menstrual cycles later . The median duration of a detectable specific HPV type is 168 days . In its P03-26 News release dated March 31, 2003, the FDA officially stated “Most women who become infected with HPV are able to eradicate the virus and suffer no apparent long-term consequences to their health. But a few women develop a persistent infection that can eventually lead to pre-cancerous changes in the cervix ” The risk of persistent HPV infection can be successfully followed and managed with an appropriate HPV DNA testing [10, 11].
Based on the existent Pap cytology and HPV screening programs available, mass HPV vaccination of young females contributes very little in further reducing cervical cancer morbidity and mortality in this country. HPV-vaccinated women must continue their regular Pap cytology and HPV screening. The public health policy should focus on offering regular quality gynecological care to all women, including education and screening for cervical precancerous changes.
(3) HPV vaccine is associated with higher rates of side effects than other childhood vaccines
Genital human papillomavirus (HPV) infection is common, but most infections are confined in the epithelium of the cervix without inducing an effective systemic immune response. This defective immune response facilitates viral persistence, a key feature of high-risk HPV infection. HPV L1 virus-like particle (VLP) vaccines are delivered by intramuscular injection. The highly immunogenic vaccines can elicit high levels of L1-specific serum neutralizing antibodies and immune memory . High levels of L1-neutralizing antibodies are needed to protect against subsequent type-specific HPV infections. However, the highly immunogenic VLPs may also cause more allergy/anaphylaxis in the vaccinated persons. The estimated rate of anaphylaxis in young women after human papillomavirus (HPV) vaccination was significantly higher – 5 to 20 fold – than that identified in comparable school-based vaccination programs . The updated VAERS-reported side effects of HPV vaccines, some resulting from allergy/anaphylaxis, are copied as follows: https://www.sanevax.org/
|Updated VAERS Reports – HPV Vaccines|
|Abnormal Pap Smear||376||376||N/A||N/A|
|Emergency Room Visit||8,733||8,562||93||78|
|Extended Hospital Stay||195||193||32||37|
|Did Not Recover||4,346||4,273||36||37|
Comments: Because of the nature of the VLPs, HPV vaccines are associated with higher frequencies of allergy/anaphylaxis reactions than other childhood vaccines. Some of the reactions may be serious, including permanent disability and possible death.
4) Safety and efficacy of HPV vaccine have not been tested among young females below age 15
The quadrivalent vaccine clinical trials against human HPV infection were reported in the FUTURE I and FUTURE II studies.
FUTURE I Study Group. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007 May 10;356(19):1928-43 .
In this series, 5455 women between the ages of 16 and 24 years who had had a lifetime number of no more than four sex partners were studied at 62 study sites in 16 countries.
- FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27. 
In this series, 12,167 women between the ages of 15 and 26 years who had had a lifetime number of no more than four sex partners were studied at 90 study sites in 13 countries.
Comments: The FDA has recently rejected approval of Gardasil for women between the ages of 27 and 45 because the efficacy of the vaccine has not been studied in this age group.
By the same reasoning, since the safety and efficacy of the quadrivalent HPV vaccine are totally unknown in women younger than age 15, the vaccine should not be used for women younger than age 15 without additional clinical data.
5) The quadrivalent HPV vaccine has not been proven as an effective cervical cancer vaccine in any age group
The endpoint adopted for efficacy evaluation of Gardasil in the clinical trial was cervical intraepithelial neoplasia 2/3 (CIN2/3) or adenocarcinoma in situ (AIS), not cervical cancer  as summarized in the FUTURE I  and FUTURE II  as follows.
FUTURE I Clinical Trial Data
Cervical Lesions with any HPV type According to grade of lesion
Total Vaccine Placebo % Efficacy (95%CI)
CIN grade 1 2713 277 363 25(12-36)
CIN grade 2 2723 102 116 13(<0-34)
CIN grade 3 2723 79 72 -9(<0-22)
AIS 2723 1 6 83(<0-100)
FUTURE II Clinical Trial Data
Cervical Lesions with any HPV type According to grade of lesion
Total Vaccine Placebo % Efficacy (95%CI)
CIN grade 2 6087 149 192 22(3-38)
CIN grade 3 6087 127 161 21(<0-38)
AIS 6087 5 83 7(<0-84)
As stated in an NCI report [Castle PE, Stoler MH, Solomon D, Schiffman M. The relationship of community biopsy-diagnosed cervical intraepithelial neoplasia grade 2 to the quality control pathology-reviewed diagnoses: an ALTS report. Am J Clin Pathol. 2007;127:805-815.]:
―.. CIN2 is not a true biologic entity but an equivocal diagnosis of precancer, representing an admixture of HPV infection and percancer. The existence of CIN2 biopsy results as a clinical entity may be the consequence of the inaccuracies of colposcopy and colposcopically directed biosy….. That CIN2 is the least reproducible of all histopathologic diagnoses may in part reflect sample error, ie, the biopsy procedure could make a CIN 1 of HPV infection appear worse by sampling the lesional area diagonally..”
In another NCI report [Castle PE, Schiffman M, Wheeler CM, Wentzensen N, Gravitt PE. Impact of improved classification on the association of human papillomavirus with cervical precancer. Am J Epidemiol. 2010 Jan 15;171(2):155-63.], it was stated:
“… there is an increasing recognition that CIN 2 is an equivocal diagnosis of precancer, an admixture of HPV infections by both carcinogenic and noncarcinogenic HPV and misclassified CIN 3. Approximately 25%–50% of CIN 2 will regress within a year or 2 years. Although CIN 3 is a better surrogate for invasive potential, it is increasingly clear that it too is heterogeneous. Only a third of CIN 3/carcinoma in situ diagnosed in women with a median age in the late 30s invaded over 30 years…”
Comments: The data in FUTURE I AND FUTURE II studies only demonstrated that HPV vaccine, Gardasil, may be effective in reducing the risk of “not a true biologic entity” lesion (CIN2) and a “heterogeneous” lesion (CIN3). Cervical cancer was not used as an endpoint for evaluation in the clinical trials.
6) The duration of immunity after HPV vaccination is about 4 years
According to NCI Factsheet Human Papillomavirus (HPV) Vaccines
How long do the vaccines protect against infection?
Comments: If young girls are HPV-vaccinated at 12 years of age, by age 16 when sexual activity starts, the immunity induced by the vaccine against type-specific HPV infection will disappear.