Hpv: Environmental Co-Factors and Prevention in the United States

HPV: Environmental co-factors and prevention in the United States

Introduction Current uses of medical technologies to prevent Cervical Cancer (CC) have proven inadequate in the further reduction of morbidity. Current medical methods are effective enough to almost completely prevent mortality from CC, but due to the inability of the US Health Care System to implement preventative measures in a timely and thorough manner, an estimated 10,400 woman will be diagnosed with CC and more than 4,000 woman will die from it in 2005. Over 6 billion dollars are spent each year on the evaluation and management of CC and Human Papilloma Virus (HPV) its primary etiological agent. This case study will analyze and describe the role of HPV and other environmental co-factors, specifically Pap testing, smoking and nutrition, in the United States which increase the risk of it’s progression into CC. Current preventative measures will be explained and an evaluation of the HPV Vaccinations effectiveness and financial viability will be analyzed as an appropriate next step to the prevention of Cervical Cancer in the United States. Cervical cancer is the third leading cause of death from malignancy in women worldwide. CC is multi-causal, and behavioral factors such as sexual practices, smoking, health screening practices and dietary habits all are important determinants of cervical cancer risk. Prevention, thus far, has been limited to Pap testing for abnormal cervical cells caused primarily by HPV, a sexually transmitted disease, which is present in 95% of CC cases. Pap tests have been implemented as a preventative service in most health facilities and Managed Care programs. If changes in cervical cells and HPV infection are identified and dealt with appropriately, CC would become a rare disease. Unfortunately, a significant percentage of the population does not have access to these services due to lack of adequate healthcare coverage, resources and access. A vaccine against HPV is currently in development, and may be released as soon as 2006. This paper will analyze the health implications of distributing the vaccine on a nation wide scale, the necessity of doing so, the financial feasability as well as who in the US population should be vaccinated. Additionally, guidelines for a nation wide, federally funded cessation program will be discussed as well as interventions for mal-nutrition that makes malignancy for more likely in under-served populations.
Background
HPV The exact process by which co-factors and HPV lead to cervical cancer is uncertain. Persistent infection with certain types of HPV is the leading cause of CC, but CC is an uncommon consequence of HPV infection. Other co-factors must be present in order for HPV to progress into CC. The CDC estimates that up to 80% of people in the US are currently or have been infected with HPV in the past. About 15% (20 million people) currently have one or more detectable genital HPV infections, with 6.2 million new genital HPV infections occurring each year. The viral etiology of HPV was suspected in 1920 and cervical tissue changes were observed for the first time through the colposcope in 1930. Around 1950 detection of the virus became a reality and its association with CC was published by Dr. Papanicolaou. In the 1970 's wide spread Pap smear testing and treatment of precancerous cells became regular practice. According to the American Cancer Society, the number of deaths from cervical cancer has dropped 74% between 1955 and 1992, mainly due to the increased use of the Pap test (Table 1). Factors contributing to the incidence of CC and HPV are lifestyle habits (smoking and diet), sexual behaviors, and certain demographics (minority and immigrant populations) which increase the risk of HPV infection and the likelihood of persistent infection and CC. Specific environmental risk factors include, but are not limited to, exposure to DES (synthetic estrogen), depressed immune system (examples include HIV or chemotherapy), sexual habits (multiple sexual partners, intercourse at a young age, history of STD’s), use of oral contraceptives or IUD, cigarette smoking (with a two-to four-fold increased incidence of CC in cigarette smokers), some vitamin/mineral deficiencies (low levels of folic acid serum levels lead to a 7.5 times greater risk of developing cervical dysplasia in a study by Kwasniewska et al), age, race (associated SES), immigrant status, healthcare coverage and the availability Pap and HPV screening.
The Pap Test The absence of Pap testing is a main predictor of CC incidence. Up to 60% of CC cases occur among women that have never been screened. Disparities exist due to the lack of healthcare and respective lack of screening in certain populations. Eighty-three percent of women report having had a Pap test in the last 3 years. Data from the 2000 national health interview survey (table 2) show that the majority of health insured women (85.8%) had been screened with considerable lower screening rates in women without health insurance (only 62%). Due to the high percentage of the US population without health insurance or access to preventative Pap testing, namely females of low socio-economic standing, recent immigrants, and women of African, Hispanic or Asian origin, the morbidity and mortality in these populations remains disproportionately high. As seen in Table 3, the incidence of CC among African Americans is 1.5 times higher than whites, and Hispanics have a rate of disease 1.5 times that of non-Hispanic (National Program for Cancer Registries and NCI’s SEER Cancer Registries). Environmental factors found to be most relevant in the progression of cervical abnormalities into CC are prevalence of HPV (with 95% of CC cases being directly related to HPV), lack of preventative screening (in 2005 50% of women with CC had not had a pap smear, and another 30% had them infrequently), and lack of follow-up after abnormal Pap tests. HPV is especially dangerous because it is sub-clinical, usually undetectable with no signs or symptoms of infection, and with only 1% of infected females exhibiting warts. An estimated 76% of the population have never heard of HPV combined with alarming rates of women not participating in screening it becomes apparent that women unknowingly put themselves at high risk of a deadly and preventable disease. Reducing the incidence of HPV would have the largest impact on morbidity and mortality of CC in the United States. The use of a vaccine to prevent the most common cancer causing strains of HPV is showing promise in being effective and cost efficient, with greater ease of distribution to the general public as compared to yearly Pap testing.
Cigarette Smoking HPV alone is not sufficient, and abnormal cell progression is dependent on the existence of other environmental co-factors(A). Cigarette smoking has been identified as one of the primary independent risk factors and research suggests that not only does it increase the likelihood of developing CC when combined with HPV, but may be independently sufficient to cause cancer of the cervix(A). According to Daling et al., the majority of recent studies have found that women who are current smokers are at increased risk for cervical neoplasia with a 1975 cohort study showing that 17% of neoplasia’s could be attributed to active and passive (second-hand) smoking. The mechanism by which smoking is involved in the pathogenesis of CC has not yet been established, though it appears that smoking may act through a combination of pathways to increase the risk of cervical cancer. Carcinogenic chemicals, including nicotine and cotinine, are present in measurable concentrations in the mucosal lining of the cervix of smokers. Ames tests indicate a 4.7 times greater likelihood of smokers than nonsmokers being positive for carcinogens.3 It is postulated that these chemicals directly contribute to cervical neoplasia by modifying DNA in cervical epithelium and contributing to the progression of cervical cancer.1 There is some evidence indicating that smoking may contribute to cervical cancer development by depressing immune response and thereby leaving the body open to pervasive long lasting infection from HPV leading to the proliferation of abnormal cells. Immunosupression has previously been identified as an associated risk factor, but not as specifically related to smoking.11
Although Smoking’s exact causal role is uncertain, research by Szarweski and Jarvis et al., found significant correlation between extent of smoking and size of minor-grade cervical lesions. Showing that a reduction in smoking leads to a reduction in the likelihood of persistent infection and progression into cancer.11 Since cigarette smoking is a modifiable behavior, it would prove valuable in strategies to prevent or decrease the high rate cervical cancers in the US. Currently, research on utilization of opportunities to promote smoking cessation in at risk populations through healthcare and community interventions is limited .
Discussion
Other contributing factors are lifestyle habits (smoking and diet), sexual behaviors, and certain demographics (minority and immigrant populations) which increase the risk of HPV infection and the likelihood of persistent infection and CC. Specific environmental risk factors include, but are not limited to, exposure to DES (synthetic estrogen), depressed immune system (examples include HIV or chemotherapy), sexual habits (multiple sexual partners, intercourse at a young age, history of STD’s), use of oral contraceptives or IUD, cigarette smoking (with a two-to four-fold increased incidence of CC in cigarette smokers), some vitamin/mineral deficiencies (low levels of folic acid serum levels lead to a 7.5 times greater risk of developing cervical dysplasia in a study by Kwasniewska et al), age, race (associated SES), immigrant status, healthcare coverage and the availability Pap and HPV screening.
Vaccination of HPV
Vaccination for HPV In 1990 clinical trials of preliminary vaccines for HPV began. The study by Taira, Neukermans and Sanders, showed that implementation of a vaccine against HPV 16 and 18 for girls and women would in all cases effectively reduce the prevalence of CC by 29.7% to 98.8% depending on the experimental scenario. The differences in effectiveness were dependent on co-vaccination of males, vaccination age, effect of vaccination over time, booster utilization and co-occurrence of Pap screening. The base-case analysis (using the current U.S. population) showed a 95.4% reduction in HPV 16 and 18 with a 61.8% lifetime reduction in CC. In all cases female vaccination was cost-effective, but only in certain scenarios was male vaccination a significant enough contributor to lowered rates of CC to be considered cost effective. Preventative screening has been the primary focus of previous attempts to ameliorate the prevalence of CC in the US. Lack of education about HPV and its strong link to CC is apparent, with statistics showing that the majority of the US population has never even heard of HPV. According to the CDC the US female population, especially those without Health insurance of lower SES, do not regularly participated in Pap testing. Even if Pap testing were made highly visible and available to the general public usage of services would still hinge on awareness of HPV and the necessity of preventative measures. A combination of public education and Pap test availability would further increase awareness and usage of services. Education about HPV and its link to CC should be provided in sex education in schools, it should be a topic of conversation between doctors and female patients, and public awareness should be promoted through TV and billboard advertisement. Strategies using prevention and education would require the government to mobilize resources and take action on a large scale. This is unlikely when evaluating the current state of US Health Policy. The inability of the US Health Care system to effectively provide preventative Pap testing to the highest risk populations has made the option of the vaccine to prevent HPV very appealing. An HPV-16/18 vaccine for 12 year old girls would reduce cohort cervical cancer cases by 61.8% (when 70% of the population is vaccinated), with a cost-effectiveness ratio of $14, 583 per quality-adjusted life year. Male co-participation in vaccination would reduce CC cases and addition 2.2% with only “incremental cost-effectiveness ratio...compared with female-only vaccination” (Taira et al.). Vaccinating girls at the onset of sexual activity leads to the greatest reduction in CC. Vaccination would have to be administered at the onset of sexual activity which may be hard to determine so it has been suggested that vaccination start at age 12 with the administration of boosters every 10 years. Even without the booster shot, vaccination would be highly effective at the reduction of HPV. The administration of a vaccine once every ten years would be more easily implemented than the once-a-year Pap test because it is less invasive and requires less followup effort on the part of the patient and provider. . Challenges will still be present even after the HPV vaccination has been approved. To make wide spread use possible it will be necessary for the vaccine to be included in state and government funded programs as well as persuading domestic private insurers to pay the estimated $225 - $350 for a course of three injections. Once the vaccine is made available the issue of distribution and reception of the vaccine must be addressed. The highest at risk populations are minority and immigrant women, and women of lower SES. Distribution problems exist as a result of cultural and external barriers. Cultural barriers may include language, low literacy, lack of familiarity with preventative concepts, lack of knowledge of how the American Health Care system works. External barriers include access to health care; lack of insurance, lack of regular healthcare provider, and logistical issues; scheduling, transportation, childcare, medical interpreters.
Cigarette Smoking There is a wealth of current research consistently showing a strong relationship between cigarette smoking and cervical cancer. Szarweski et al noted that some research has suggested that there is an over estimation of risks due to smokers’ participating in higher risk sexual behaviors but that in their research the link between smoking and cervical cancer was still strong even after adjusting for possible confounding factors including age, race, SES and sexual behaviors. More research is needed to verify the specific causal role(s) of smoking to cervical cancer, and to what extent other behaviors participated in by smokers may contribute to their increased risk.
Whether smoking’s contribution to increased rates are due to carcinogenic chemicals being stored in cervical mucosal lining, causing DNA degradation, or through immunosuppressive tendency of smoking and its association with increased risk of cervical neoplasia is of minor importance in the decision to include smoking cessation as part of cervical cancer prevention programs. Members of racial and ethnic minority groups and individuals of lower SES engage in higher risk smoking behaviors and suffer disproportionately from tobacco related illness and death. Not surprisingly these same groups have the highest morbidity and mortality from cervical cancers.
Recommendation
Vaccination should be easier to implement as compared to the Pap test for two reasons. One, the Vaccine is less invasive and does not require genital inspection, and therefore cultural differences in modesty will not be a factor. Second, the vaccine only needs to be administered once to decrease the likelihood of CC by as 29.7%, and every 10 years to lead to a reduction as high as 95.4% (Taira et al.). In comparison to the yearly Pap smear, adherance woul require less logisitical barriers including childcare, transportation, and scheduling simply due to the decreased frequency of the test. Initial vaccination should administered at 12 years of age and schools should maintain record for the first vaccination. Once vaccination becomes wide spread within the governmental and private health care sectors and preventative programs (as Pap testing has), it will be possible to remind those with health insurance that it is time for vaccination and to direct students without health insurance or a regular practitioner to a nearby facility in which they can receive their vaccination free or at a low cost. The implementation of vaccination in just 70% of the population would have a significant (90% reduction in HPV 16/18) impact on the morbidity and mortality of cervical cancer. In order to meet the general health care needs of the public (especially the under-served and minority populations it is unlikely that preventative Pap testing and education about high risk activities and behavioral modification will decrease the morbidity and mortality of CC any further. Vaccination of the highest at-risk populations would be the most effective and direct way to decrease Cervical Cancer in the US.
It is important that we address factors other than HPV in the development of cervical cancer. Cigarette smoking is not only a significant exposure in the risk of development of precancerous lesions but is a modifiable exposure. If women can be educated about the risk associated with this activity and an increase in smoking cessation implemented, cervical cancer morbidity and mortality would decrease. Due to the disproportionately higher negative health effects of tobacco on underserved populations and higher rates of cervical cancer, a strategy for smoking cessation must address these disparities. In 2002 the Subcommittee on Cessation of the Interagency Committee on Smoking and Health (ICSH) developed a National Action Plan for Tobacco Cessation. This plan will directly effect the number of woman who are at increased risk of cancers due to their smoking and provides a good example for future intervention strategies. Federal initiatives suggested by the ICSH include; a nationwide tobacco cessation outline, a multi-faceted, paid national media campaign, insurance coverage of tobacco dependence treatment, new tobacco research infrastructure, new tobacco training infrastructure, smokers health fund, and earmarking funds for cessation. Figure 1 describes ICSH’s federal recommendations in detail. It is estimated that this strategy will encourage 4.7 million smokers to quit and prevent 6 million youths from starting, with the added benefit of contributing to a decrease in smoking in populations at risk of developing highly preventable cervical cancer.

Bibliography .Fagan, P., et al. Eliminating Tobacco-Related Health Disparities: Directions for Future Research. American Journal of Public Health. 2004; 94;2:211-217.

Bibliography: .Fagan, P., et al. Eliminating Tobacco-Related Health Disparities: Directions for Future Research. American Journal of Public Health. 2004; 94;2:211-217.