Cervical cancer and smoking

Basic Information About Cervical Cancer

This diagram shows different parts of a woman’s reproductive system.

Cancer is a disease in which cells in the body grow out of control. Cancer is always named for the part of the body where it starts, even if it spreads to other body parts later. When cancer starts in the cervix, it is called cervical cancer. The cervix connects the vagina (birth canal) to the upper part of the uterus. The uterus (or womb) is where a baby grows when a woman is pregnant.

All women are at risk for cervical cancer. It occurs most often in women over age 30. Long-lasting infection with certain types of human papillomavirus (HPV) is the main cause of cervical cancer. HPV is a common virus that is passed from one person to another during sex. At least half of sexually active people will have HPV at some point in their lives, but few women will get cervical cancer.

Cervical cancer is highly preventable in most Western countries because screening tests and a vaccine to prevent HPV infections are available. When cervical cancer is found early, it is highly treatable and associated with long survival and good quality of life.

Are you worried about the cost? CDC offers free or low-cost cervical cancer screening tests. Find out if you qualify.

Almost all cervical cancers are caused by HPV. Other things also can increase your risk of cervical cancer.The most important thing you can do to help prevent cervical cancer is to have regular screening tests starting at age 21.Early on, cervical cancer may not cause signs and symptoms. Advanced cervical cancer may cause bleeding or discharge from the vagina that is not normal for you.Two screening tests can help prevent cervical cancer or find it early: the Pap test (or Pap smear) and the HPV test.Your Pap test will come back as “normal,” “unclear,” or “abnormal.” If you also have an HPV test, it will come back as either “positive” or “negative.”Cervical cancer is treated in several ways. It depends on the kind of cervical cancer and how far it has spread. Treatments include surgery, chemotherapy, and radiation therapy.

Cervical cancer

Find out about the risks and causes of cervical cancer, including the human papilloma virus (HPV).

Cervical cancer is the 13th most common cancer in women in the UK.

Anything that increases your risk of getting a disease is called a risk factor. Different cancers have different risk factors.

Having one or more risk factors does not mean that you will definitely get cervical cancer.

Age

Cervical cancer is more common in younger women. More than half of the cervical cancer cases in the UK each year are diagnosed in women under the age of 45.

Human Papilloma Virus (HPV) infection

The human papilloma virus (HPV) is a major cause of the main types of cervical cancer.

HPV is common. Most sexually active people come into contact with HPV during their lifetime. But for most the virus causes no harm and goes away on its own.

Types of HPV

There are many different types of HPV. Most are harmless but some cause genital warts, and others cause changes that can develop into cancer. As well as cervical cancer, HPV can cause anal, vaginal, vulval, penile and some types of mouth and throat cancers. HPV can be passed on through close skin to skin contact, usually during sexual activity.

Around 12 types of HPV are considered high risk for cancer of the cervix. Two of these types (HPV 16 and HPV 18) cause about 7 out of 10 (70%) cervical cancer cases.

For most people, the immune system clears the HPV infection within 2 years. But sometimes this doesn’t happen. If you have a long lasting (persistent) infection with a high risk type of HPV, you are more at risk of developing cervical cancer.

Sex

Practising safer sex by using barrier methods like condoms will reduce your risk of getting HPV and passing it on. But they won’t protect you completely. Practising safer sex will also help to protect you against many sexually transmitted diseases.

Vaccines

There are now vaccines to prevent HPV infection. All girls aged 12 or 13 in the UK are routinely offered the HPV vaccine at school. These vaccines protect against the types of HPV that are most likely to cause cervical cancer. But they don’t protect against all types. So you still need to take part in cervical screening, even if you have had the HPV vaccine.

Human immunodeficiency virus (HIV)

Having human immunodeficiency virus (HIV) or AIDS increases the risk of developing cervical cancer. This risk might be reduced in women who are having treatment for HIV.

Other sexually transmitted infections

The risk of cervical cancer may be increased in women who have a sexually transmitted infection (STI) alongside HPV.

Women with both HPV and chlamydia (pronounced klah-mid-ee-ah), might have a higher risk of cervical cancer.

Smoking tobacco

Smoking tobacco increases your risk of getting cervical cancer. The risk increases with the more cigarettes you smoke a day and the younger your age when you start smoking.

Smoking also makes it harder to treat abnormal cells on your cervix.

It’s never too late to stop smoking but the sooner you stop the better.

Contraceptive pill

1 in every 10 cases of cervical cancer is linked to taking the contraceptive pill.

Taking the pill for more than 5 years increases the risk of cervical cancer. The increased risk begins to drop as soon as you stop taking it. After 10 years the risk is the same as if you had never taken it.

The pill can also slightly increase the risk of breast cancer. But it is important to know that taking the pill can help reduce the risk of womb and ovarian cancers.

How many children you have, and when

Women who have had children are at an increased risk of cervical cancer compared to those who haven’t.

Having your first baby before the age of 17 also gives a higher risk, compared to women who had their first baby after the age of 25. The reasons for this are unclear.

Family history

You have an increased risk of cervical cancer if your mother, sister or daughter has had cervical cancer. We don’t know whether this is linked to faulty genes, or whether it is due to common shared factors like smoking.

Previous cancer

You have an increased risk of cervical cancer if you have had cancer of the:

  • vagina
  • vulva
  • kidney
  • urinary tract (includes the bladder and the tubes from the kidneys to the bladder)

One of the reasons for this might be previous radiotherapy treatment.

For detailed information on cervical cancer risks and causes

Stories about potential causes are often in the media and it isn’t always clear which ideas are supported by evidence. There might be things you have heard of that we haven’t included here. This is because either there is no evidence about them or it is less clear.

Cervical screening

Regular cervical screening can prevent cervical cancer by picking up abnormal cell changes in the cervix. These changes could lead to cancer if left untreated.

Cervical screening is available for women between the ages of 25 to 64.

Cervical cancer

Each year, more than 13,000 women in the United States are diagnosed with cervical cancer.

No woman knows if or when she will receive a diagnosis of cervical cancer, but routine Pap testing may help detect abnormal changes to the cervix before cancer has a chance to develop. That is why women who do not regularly have a Pap test are at increased risk of developing cervical cancer.

What causes cervical cancer?

Cervical cancer forms when the DNA in cells in the cervix mutate or change. In some cases, these mutated cells grow out of control, forming a tumor in the cervix.

Cervical cancer is almost exclusively caused by a human papillomavirus (HPV) infection, although not all women with an HPV infection will develop cervical cancer. Girls and young women who are treated with the HPV vaccine have a significantly reduced risk of developing cervical cancer later in life.

Known risk factors for cervical cancer include:

Lifestyle

Sexual history: Certain types of sexual behavior are considered risk factors for cervical cancer and HPV infection, including early onset of sexual activity (beginning in the early teen years), sex with multiple partners, and sex with someone who has had multiple partners.

Smoking: A woman who smokes doubles her risk of cervical cancer, because carcinogens that are inhaled are partly excreted in cervical mucus and bathe the cervix.

Other conditions

HPV: Although HPV often causes cancer, having HPV does not mean you will get cancer. For most women, the HPV virus goes away on its own, or the women undergo treatments to remove the abnormal cells. HPV is a skin infection, spread through skin-to-skin contact with a person who has the virus.

Weakened immune system: In most people with healthy immune systems, the HPV virus clears itself from the body within 12 to 18 months. However, people with HIV are at an increased risk, as are those who are chronically immunosuppressed, such as transplant patients or those with another chronic or acute illness.

Diethylstilbestrol (DES): Women whose mothers took DES, a drug given to some women to prevent miscarriage between 1940 and 1971, have a higher risk of developing cervical cancer.

Additional facts about HPV:

  • There are more than 100 types of HPV, 30 to 40 of which are sexually transmitted.
  • Of these, at least 15 are high-risk HPV strains that can cause cervical cancer. The others may genital warts or cause no symptoms.
  • Up to 80 percent of women and men will contract HPV in their lifetime. For most people with a healthy immune system, the virus disappears from the body within one to three days. Some high-risk strains carry a much higher risk of causing cervical cancer.
  • A healthy immune system will usually kill the HPV virus, including the high-risk types of HPV.
  • Only a small percentage of women with high-risk HPV develop cervical cancer.

Next topic: What are the symptoms of cervical cancer?

E-cigarettes: Safe to recommend to patients?

Most people assume that electronic cigarettes (e-cigarettes) are safer than conventional tobacco products. Nevertheless, we should not encourage addicted smokers to try “vaping” as an alternative to nicotine replacement therapy, and we should discourage never-smokers from taking up vaping as vigorously as we try to discourage them from taking up smoking.

This article examines the prevailing assumptions and the evidence regarding the safety of e-cigarettes and traditional nicotine replacement therapy.

SMOKING IS DECLINING BUT FAR FROM GONE

While smoking rates have been declining over the past 50 years, the burden of disease attributable to tobacco use remains high. In the United States, it is estimated that nearly 6 million of those currently under the age of 18 will die of tobacco-related illnesses.1 In the 50 years since the US surgeon general first reported on the health concerns related to tobacco, smoking has claimed the lives of nearly 21 million Americans1 and continues to kill more than 400,000 every year.2

Even though the risks of smoking are well known, smoking remains one of the most difficult habits to quit. Indeed, about half of all smokers attempt to quit each year, but very few succeed.3

NICOTINE REPLACEMENT: GUM, PATCHES…E-CIGARETTES?

Nicotine replacement therapy was born out of the thought that, though nicotine is responsible for tobacco’s addictive quality, most tobacco-related disease is attributable to the 7,000 other substances found in tobacco smoke.4 Nicotine polacrilex gum was approved by the US Food and Drug Administration (FDA) in 1984, and nicotine transdermal film was approved in 1991.5

Nicotine replacement therapy, in the form of patches and gum, has been shown to improve the odds of successfully quitting smoking by a factor of nearly 1.5 to 2.6 Nicotine patches and gum were initially prescription medications but became available over the counter in 1996.7 They quickly became first-line agents for smoking cessation, and their over-the-counter availability softened any potential concerns about the possible deleterious health consequences of nicotine itself.

E-cigarettes—devices that generate a nicotine vapor that can be inhaled in a fashion that mimics the experience of smoking—were introduced in China in 2004.8 By 2012, sales of these devices in the United States had reached $500 million and in 2013 were expected to top $1 billion.9,10

E-cigarette manufacturers make no therapeutic claims about their products, thus allowing them to escape regulation by the FDA as nicotine replacement therapy. A recent FDA proposal, however, is likely to change their “protected” status.11 Despite the lack of regulation up to this point, patients generally assume that e-cigarettes are just another form of nicotine replacement therapy, even though they contain substances other than nicotine.

WHAT’S IN E-CIGARETTES?

Nicotine, which is bad in itself

E-cigarettes contain nicotine in varying amounts (some cartridges contain none at all). Though nicotine replacement therapy is less harmful than tobacco, nicotine by itself is associated with its own health problems, notably cancer, cardiovascular disease, birth defects (possibly), and poisoning.

Carcinogenesis. Nicotine plays a direct role in carcinogenesis through a variety of mechanisms, including increasing the activity of tumor growth-promoting transcription factors, decreasing apoptosis, and increasing angiogenesis in tumors.12 Additionally, specific types of nicotinic acetylcholine receptors— eg, alpha 7 receptors, which are stimulated by nicotine—are found in many malignant tumors and are thought to play a role in tumor progression.12 Blockade of alpha 7 nicotinic acetylcholine receptors has been shown to decrease the growth of certain cancers.12

However, these findings were from in vitro studies, and the concerns they raised have not been reflected in in vivo studies. Despite having been on the market for 30 years, nicotine replacement therapy has as yet not been associated with any “real world” increase in cancer risk.

Smoking is one of the leading risk factors for cervical cancer, and nicotine itself may play a contributing role. Nicotine has been shown to increase cellular proliferation in cervical cancer.13 Some evidence suggests that it may also play a role in the lymphogenic metastasis of cervical cancer.13

Cardiovascular disease. Nicotine has been linked to cardiovascular disease. It directly affects the heart’s rate and rhythm via nicotinic acetylcholine receptors in the peripheral autonomic nervous system. It impairs endothelial-dependent dilation of blood vessels in response to nitric oxide, and this inhibition in the coronary arteries may contribute to smoking-related heart disease.14,15 Nicotine has also been shown to raise serum cholesterol levels, increase clot formation, and contribute to plaque formation by increasing vascular smooth muscle.14

Possible teratogenic effect. There is some theoretical concern regarding exposure to nicotine in utero, as nicotinic acetylcholine receptors develop before neurons, and nicotine may therefore interfere with the natural influence of acetylcholine on the development of this system.14

Direct toxicity. Nicotine is toxic at high levels. The overdose potential associated with nicotine is particularly worrisome with e-cigarettes, as the nicotine solution they use is typically supplied in 5-mL, 10-mL, or 20-mL vials that range in concentration from 8.5 to 22.2 mg of nicotine per mL.16 The fatal single dose range of nicotine has been reported at 30 to 60 mg in adults and 10 mg in children and can be achieved by oral, intravenous, or transdermal absorption,16 so one vial, if consumed orally, could be fatal.

The number of calls to US poison control centers regarding e-cigarettes has increased, closely paralleling their rise in popularity. In 2010, there were only 30 e-cigarette related calls to poison control centers; in 2011 the number increased to 269, and in 2012 it had reached 459 and included one fatality that was deemed a suicide.17–19 Even though such toxic nicotine overdoses are rare, physicians should exercise caution and avoid recommending e-cigarettes to individuals with mental confusion, psychotic disorders, or suicidality, who might consume an entire vial.

Possible positive effects? Smoking is one of the worst things that people can do to their body, but the picture is complicated by a few possible positive effects. In the brain, although smoking increases the risk of Alzheimer disease, it is associated with a lower risk of Parkinson disease. In the bowel, it increases the risk of Crohn disease but may decrease the risk of ulcerative colitis. Gahring and Rogers20 pointed out that neuronal nicotinic receptors are present in nonneuronal cells throughout the body and proposed that expression of these receptors may play a role in mediating the consequences of nicotine use, both good and bad. The lesson may be that nicotine is very active in the body, its effects are complicated and still incompletely understood, and therefore we should not encourage people to inhale nicotine products ad lib.

Additives

E-cigarettes typically contain propylene glycol, flavorings, and glycerine. One study that analyzed the additive contents of e-cigarettes found that propylene glycol accounted for 66% of the fluid, glycerine 24%, and flavorings less than 0.1%.21 Propylene glycol is the substance typically used in theater fog machines and is used to generate the vapor in e-cigarettes. Other substances such as tobacco-specific nitrosamines and diethylene glycol have also been found in e-cigarettes in small amounts.22

Propylene glycol, ‘generally recognized as safe’

Propylene glycol has been used in theater fog machines for years—think Phantom of the Opera. It is also widely used as a solvent in many consumer products and pharmaceuticals. The FDA classified it as “generally recognized as safe” on the basis of one study conducted in rats and monkeys over 60 years ago.23 As other authors have noted, however, a major manufacturer of propylene glycol recommends that exposure to propylene glycol mist be avoided.24,25 Potential concern over propylene glycol mist was heightened when it was discovered that of all industries, the entertainment business ranked first in terms of work-related asthma symptoms and had the fifth-highest rate of wheezing.26,27

Studies conducted over the last several decades have raised numerous health concerns about the safety of propylene glycol (Table 1).26,28–36 The studies of propylene glycol fog are particularly important, as they most closely resemble the route of exposure in e-cigarette users.

Wieslander et al28 exposed 27 volunteers to propylene glycol mist for 1 minute in an aircraft simulator under training conditions. Exposures were high, ranging from 176 to 851 mg/m3 (mean = 309 mg/m3). Four volunteers who developed a cough exhibited evidence of airway obstruction as indicated by a 5% decrease in forced expiratory volume in 1 second (FEV1), while the rest did not exhibit any change in FEV1.

Moline et al29 conducted a non-peer-reviewed study for the Actors Equity Association and the League of American Theaters and Producers of 439 actors exposed to theater fog. They found statistically significant evidence of throat and vocal cord inflammation with prolonged peak exposure to glycols and recommended that actors not be exposed to glycol concentrations exceeding 40 mg/m3.

Varughese et al26 conducted a study in 101 volunteers at 19 sites. The mean concentration of glycol-based fog was much lower than that in the studies by Wieslander et al28 and Moline et al,29 at 0.49 mg/m3 (the maximum was 3.22 mg/m3). The investigators concluded that glycol-based fog was associated with deleterious respiratory effects and that employees’ exposure should be limited.

The health issues related to propylene glycol are unique to e-cigarettes compared with nicotine replacement therapy. Unfortunately, the most applicable data available are from studies of persons exposed to theater fog, which involved periodic exposure and likely do not emulate the deep inhalation, multiple times daily, of propylene glycol by e-cigarette smokers. A 2014 review of the chemistry of contaminants in e-cigarettes37 concluded that estimated levels of propylene glycol exposure in e-cigarette users come close to the threshold limit value set by the American Conference of Governmental Industrial Hygienists, and should merit concern.

These studies and real-life experience in the theater, while limited in scope, should give physicians pause and should cause increased awareness of the possibility of e-cigarette-induced pulmonary and upper airway complications. If such complications should occur, discontinuation of vaping should be advised.

Nov. 17, 2006 — HPV, the human papillomavirus, is vastly more dangerous in women who smoke, a Swedish study finds.

Some 19 kinds of HPV have been linked to cervical cancer; HPV-16 is the most deadly.

Now, research suggests that women who smoke are more likely to get cervical cancer if they become infected with that virus than are nonsmokers.

While the nonsmokers studied were six times as likely to develop cancer if infected, smokers were more than 14 times as likely to get cancer within nine years if they had the virus, according to the study.

Researchers Anthony S. Gunnell and his colleagues at Sweden’s Karolinska Institute suspected smoking and HPV-16 might work together.

So they compared the medical records of 375 women who had the earliest stage of cervical cancer to the records of 363 women with similar characteristics who did not have the cancer.

Based on Pap smears taken an average of nine years before the women developed cervical cancer, the researchers were able to tell whether the women had had an HPV-16 infection.

They also were able to see whether the women had had high or low levels of HPV in their blood — something doctors call high or low viral load.

The results:

  • Among smokers, those who had tested positive for HPV-16 were 14.4 times more likely to get cervical cancer than those who did not have the infection.
  • Among smokers, those who had had high HPV-16 viral load were 27 times more likely to get cervical cancer than those who did not have the infection.
  • However, among nonsmokers, those who had tested positive for HPV-16 were only six times more likely to get cervical cancer than nonsmokers who did not have the infection. Having high vs. low HPV-16 viral load did not affect that statistic.

Women who had continued to smoke further multiplied their chances of getting cervical cancer.

The researchers suggest smoking may help HPV-16 grow faster — possibly by slowing helpful immune responses.

They also suggest smoking may speed the process by which HPV-16 causes cancer.

The findings appear in the November issue of Cancer Epidemiology, Biomarkers & Prevention.

Send to KindleDoes vaping cause cervical cancer? Read this blog post to find out!

There’s been a lot of talk lately about the safety of vaping. The news has many questioning its safety and asking: Does vaping cause cervical cancer? The truth is, vaping should be used responsibly by choosing the correct devices and being smart about what kinds of substances you are using with it.

What is Vaping?

Vaping, also known as e-cigarettes, refers to a battery-powered device that heats up liquid to form vapors that can be inhaled for enjoyment. The substances that people put in vape pens and e-cigarettes vary and may be the link behind the question, does vaping cause cervical cancer? Certain substances such as THC and nicotine can be much more harmful than others. Some of the substances used for vaping include:

  • Flavored Tobacco
  • CBD Oil
  • Nicotine
  • Marijuana (THC)
  • Other Potentially Harmful Substances

Vaping Dangers for Women

Vaping is still relatively new and therefore studies are just now being conducted on their long-term effects. But, there are things that we do know from long-term studies based on regular cigarette usage and other devices used to smoke substances.

Nicotine is Addictive

It doesn’t matter whether you’re smoking an old fashioned cigarettes or vaping, any way you slice it, nicotine is highly addictive and can lead to health issues caused by overuse of the product. Nicotine causes you to crave more smoke, and when you don’t get it, users suffer withdrawal symptoms. Nicotine has been linked to cervical cancer, especially among patients who have contracted the highly common Human Papillomavirus (HPV). So, does vaping cause cervical cancer? It’s a possibility, especially if you’re using nicotine and you’ve been exposed to HPV.

Dangers of Vaping Marijuana (THC)

Recent news reports about vaping related illnesses and deaths have been linked to marijuana use. Vaping THC, which is the compound in marijuana that gets you high, may be even more dangerous than smoking it the old fashioned way. Researchers say the common link between all the vaping related health concerns was that they were all consuming THC; therefore, health officials are advising against using your vaping devices for this purpose.

Can You Vape Safely?

If you choose to vape, you should do it responsibly. Choose high quality devices from a reputable manufacturer, and try to avoid THC and nicotine. One option that may be therapeutic, as well as enjoyable is vaping CBD.

CBD oil vaping liquid is made from hemp and does not contain THC. When choosing a CBD vape product, you want to make sure it does not contain added chemicals that can be toxic. Those chemicals include:

  • Propylene Glycol (PG)
  • Polyethylene Glycol (PEG)
  • Vegetable Glycerin (VG)
  • Ethanol
  • Alcohol

So, does vaping cause cervical cancer and other health issues? This truth is… it likely can, if you use products and devices that contain nicotine, THC, and toxic additives. So, if you choose to vape, do it responsibly.

Is Vaping Safe for Women? (Does Vaping Cause Cervical Cancer?)

Does vaping cause cervical cancer? Read this blog post to find out!

There’s been a lot of talk lately about the safety of vaping. The news
has many questioning its safety and asking: Does vaping cause cervical cancer?
The truth is, vaping should be used responsibly by choosing the correct devices and being smart
about what kinds of substances you are using with it.

Stop Smoking and Reduce Your Cervical Cancer Risk

If you have human papillomavirus (HPV), the virus that causes cervical cancer, you can reduce your risk of developing cervical cancer by quitting smoking and staying away from people who smoke.

The U.S. Surgeon General has identified cervical cancer as strongly associated with smoking tobacco. And although cervical cancer is caused primarily by HPV, cigarette smoking is considered a cofactor, which means that certain types of HPV and cancer-causing chemicals related to smoking may work together to increase your likelihood of developing cancer.

“The more you smoke, the more your risk goes up. Not only that — there is also a huge association with secondhand smoke. Even three or four hours a day of passive smoke raises your risk,” says gynecologist Rachel Reitan, MD, assistant professor of obstetrics and gynecology at the Tulane University School of Medicine. “Stay away from smoking, and stay away from people who smoke.”

Cervical Cancer and Smoking

A study published in the Journal of the American Medical Association showed that the risk of cervical cancer increased in women who were smokers and in women who were exposed to secondhand smoke even after other factors, such as sexual activity, were taken into account. Women who were exposed to three or more hours of smoke a day had about three times the risk of cervical cancer, and current smokers were found to have 3.4 times the risk of cervical cancer.

How Smoking May Cause Cervical Cancer

The way smoking contributes to cervical cancer is not fully understood. But researchers believe tobacco smoke combined with HPV might become a cervical cancer cause because:

  • Smoking might prevent the body’s immune system from effectively fighting HPV.
  • Carcinogens from smoking amplify the effect of HPV infection in cervical cells.
  • Carcinogens from smoking may move the cancer-growing genetic code more quickly from the virus to cervical cells, especially with the strains of HPV that pose the greatest risk of causing cancer.

“We assume smoking affects immunity,” says Dr. Reitan. She says women who have HPV and smoke more than a pack a day significantly increase their risk of developing cervical cancer.

A study performed in Washington showed that after two years, women who quit smoking had the same risk of cervical cancer as women who never smoked. The same study showed that women with active cervical cancer during the screening period were more likely to be those who smoked at least 10 cigarettes a day than nonsmokers. Researchers in this study concluded that women who have HPV should not smoke or should cut down on how much they smoke if they want to reduce their cancer risk.

The U.S. Department of Health and Human Services offers the following tips for preventing cervical cancer:

  • Don’t smoke.
  • Get regular Pap smears.
  • Eat a healthy diet rich in fruits and vegetables.
  • Use a condom.
  • Be monogamous.

Bottom line: You can take action to lower your risk of cervical cancer. Reducing your exposure to smoke is among the best steps you can take.

PMC

Since most HPV infections are spontaneously cleared (4), viral persistence and viral load are thought to be necessary for cancer progression (12, 16). Multiple epidemiological studies have suggested a correlation between cigarette smoking among HPV-infected women as a cofactor for the development of cervical cancer (8, 13, 15). Using organotypic “raft” cultures, we studied the effect of BaP, a major carcinogenic component of cigarette smoke, on the productive life cycle of three high-risk HPV types (1). To date, raft cultures are the best physiologically relevant in vitro model system available, one which closely mimics the natural replication of the virus as it occurs in vivo (7). We showed that treatment with 1 μM BaP resulted in a 10-fold increase in viral titers while treatment with 0.001 μM BaP resulted in a 2-fold increase in the number of genome copies (1). Thus, our studies suggest that exposure to cigarette smoke carcinogens such as BaP could lead to manipulation of host cell- and/or HPV-specific functions resulting in enhancement of the “total viral load,” with respect to both increased virion synthesis and viral genome amplification. Increased viral titers may be important for infection of secondary sites around the primary lesion, and an increase in the number of genome copies may result in a concomitant increase in the number of templates from which the E6 and E7 oncogenes may be transcribed (5). Upregulation of genome amplification may also increase the probability of viral DNA integration into the host genome, a milestone in the development of cervical cancer. Based on our studies, we present a novel finding that BaP-regulated enhancement of both virion synthesis and amplification of genome copies may potentially result in increased persistence of the virus in HPV-infected women who smoke.

While BaP has been detected in cervical mucus, its concentration has yet to be determined (6). In contrast, other cigarette smoke components have been found in measurable concentrations within a variable range. Our rationale for choosing the range of BaP concentrations tested was based on published data on other cigarette smoke carcinogens which have been quantified in cervical mucus. For example, nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a well-characterized cigarette carcinogen, has been detected at a concentration as high as 0.56 μM (9), whereas noncarcinogenic components such as nicotine and its metabolite cotinine have been detected at concentrations of 3 μM and 0.36 μM, respectively (11). Interestingly, both nicotine and cotinine were found to be strongly concentrated in the cervical mucus in comparison to their levels in serum (3). With respect to this issue raised by Dr. Castle, we would like to point out that no studies have been performed to actually measure BaP concentrations within cervical cells or, for that matter, any other cigarette carcinogen. It may be assumed that active or passive cellular processes concentrate BaP and its metabolites inside or outside the cell depending on a variety of conditions related to the dynamics of cellular homeostasis, which in turn may be dependent on the number of cigarettes smoked per day. In our opinion, intracellular concentrations of BaP and its concentration in the cervical mucus bathing the extracellular surfaces may in combination determine the effective BaP concentration and its ultimate effect on the viral life cycle.

Our published studies did not reflect a linear dose dependence of HPV genome amplification upon BaP treatment because we reported the results obtained at data points using serial 10-fold decreases in BaP final concentrations (1). However, our unpublished studies did show a bimodal BaP dosage response when a wider range of BaP concentrations was utilized (Fig. ​(Fig.1).1). Our studies showed that treatment with low concentrations of BaP increased genome amplification, and increased amplification has previously been shown to correlate with increased oncogene expression (5). In addition, high levels of E6/E7 transcript expression have been well correlated with the viral DNA load (10) as well as with poor prognosis in cervical cancer patients (2, 14). On the other side of the spectrum, it is a moot point to argue whether or not the dosage effect of BaP has a linear response on HPV genome amplification, especially since the end point of our assay measured the production of infectious virus, which is a definitive stage of the viral life cycle.

Southern blotting and densitometric analysis were performed to determine the effect of BaP treatment on HPV31b genome copies. Five micrograms of total cellular DNA was digested with HindIII, which linearizes the HPV31b genome at nucleotide 2455. Blots were detected with 32P-labeled total HPV31-specific DNA probe generated by random primer extension, followed by autoradiography. Densitometric analysis was then performed with the FIII bands from Southern blots of BaP treatments, and results were compared with those of no-BaP controls, which was set to 1. Results indicate analysis of one representative experiment.

While the Hybrid Capture 2 assays presented by Dr. Castle are informative, they are as yet inconclusive. We would like to respectfully point out that these assays are designed to measure a type of end point which is significantly different from those used in our studies and unsuitable for side-by-side comparisons. The differences are attributed to the types of tissues used in these instances. The Hybrid Capture 2 assays utilized exfoliated cells, and the limitations to using these types of patient samples have been pointed out by Dr. Castle. In comparison, we used raft tissues which were derived from a well-defined homogeneous system and which are amenable to reproducible results over multiple experiments (1).

Our initial studies were started based on the epidemiological studies which first proposed the connection between cigarette smoking and the increased risk of developing cervical cancer (15). Our findings have yielded some unexpected yet exciting data which suggest that cigarette smoke carcinogen exposure increases HPV viral load with respect to both virion synthesis and genome copies. On the other hand, much has been published regarding the current ideas on the positive relationship between persistent HPV infections and viral loads as a possible link in cancer progression (16). Thus, our studies provide the basis for a marriage of the two ideas, in turn giving rise to the novel possibility that exposure to cigarette carcinogens induces robust conditions (virus and/or host cell specific) which positively support persistence of the virus. Our studies provide a foundation for examining the molecular mechanisms by which carcinogenic constituents of cigarette smoke regulate host cellular factors as well as the viral life cycle which together may determine cervical carcinogenesis.

ON THIS PAGE: You will find out more about the factors that increase the chance of developing cervical cancer. Use the menu to see other pages.

A risk factor is anything that increases a person’s chance of developing cancer. Although risk factors often influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. Knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.

The following factors may raise a woman’s risk of developing cervical cancer:

  • Human papillomavirus (HPV) infection. The most important risk factor for cervical cancer is infection with HPV. HPV is common. Most people are infected with HPV when they become sexually active, and most people clear the virus without problems. There are over 100 different types of HPV. Not all of them are linked to cancer. The HPV types, or strains, that are most frequently associated with cervical cancer are HPV16 and HPV18. Starting to have sex at an earlier age or having multiple sexual partners puts a person at higher risk of being infected with high-risk HPV types.

  • Immune system deficiency. Women with lowered immune systems have a higher risk of developing cervical cancer. A lowered immune system can be caused by immune suppression from corticosteroid medications, organ transplantation, treatments for other types of cancer, or from the human immunodeficiency virus (HIV), which is the virus that causes acquired immune deficiency syndrome (AIDS). When a woman has HIV, her immune system is less able to fight off early cancer.

  • Herpes. Women who have genital herpes have a higher risk of developing cervical cancer.

  • Smoking. Women who smoke are about twice as likely to develop cervical cancer as women who do not smoke.

  • Age. People younger than 20 years old rarely develop cervical cancer. The risk goes up between the late teens and mid-30s. Women past this age group remain at risk and need to have regular cervical cancer screenings, which include a Pap test and/or an HPV test.

  • Socioeconomic factors. Cervical cancer is more common among groups of women who are less likely to have access to screening for cervical cancer. Those populations are more likely to include black women, Hispanic women, American Indian women, and women from low-income households.

  • Oral contraceptives. Some research studies suggest that oral contraceptives, which are birth control pills, may be associated with an increase in the risk of cervical cancer. However, more research is needed to understand how oral contraceptive use and the development of cervical cancer are connected.

  • Exposure to diethylstilbestrol (DES). Women whose mothers were given this drug during pregnancy to prevent miscarriage have an increased risk of developing a rare type of cancer of the cervix or vagina. DES was given for this purpose from about 1940 to 1970. Women exposed to DES should have an annual pelvic examination that includes a cervical Pap test as well as a 4-quadrant Pap test, in which samples of cells are taken from all sides of the vagina to check for abnormal cells.

Research continues to look into what factors cause this type of cancer, including ways to prevent it, and what women can do to lower their personal risk. There is no proven way to completely prevent this disease, but there may be steps you can take to lower your cancer risk. Talk with your health care team if you have concerns about your personal risk of developing cervical cancer.

The next section in this guide is Screening and Prevention. It explains how tests may find precancer and cancer before signs and symptoms appear. Use the menu to choose a different section to read in this guide.

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