DANGEROUS Liasons : A Mysterious, Sexually Transmitted Virus Threatens to Trigger a New Epidemic

THERE IS SOMETHING pure and innocent about Patty and Victor Vurpillat. She was 18 and he was 19 when they met in 1988. They fell in love. She moved in. Within 10 months, they were married. Everybody freaked, as Victor tells it; it was like the 1950s.

The newlyweds found a sunny little apartment in Pacific Palisades. She stocked the refrigerator with health food and began training for a marathon. He enrolled at Santa Monica College, bringing home A’s and Bs. Conversation turned to babies.

But then Patty and Victor came down with a most un-1950s disease--a condition fraught with all the uneasiness of sexual relations in the age of AIDS, caused by a virus with disturbing links to cancer that threatens to become the venereal disease of the 1990s.

It all started with some bumps on Patty’s cervix. Genital warts, the nurse-practitioner at the clinic pronounced them. A closer examination turned up an area of abnormal tissue. The clinic recommended a biopsy to check for signs of cancer.

Suddenly Patty was on her back with a microscope perched between her thighs. A nurse peered in and snipped away at her insides. Later, Patty returned to have the warts frozen off. It was creepy: She could feel her cervix defrost.

Victor, too, had to be vetted. There he lay, in a women’s clinic, surrounded by women. They put his feet up in stirrups; there were little mittens on the stirrups. Two nurses set about removing tiny warts, one by one.

Back at home, panic colored Patty’s thoughts: She would get cancer; she would have a hysterectomy; there would never be any children. She tried reminding herself that the risk was small. But fear ached in her gut.

“It was just awful--not knowing what’s going on with your body and if you’re going to be OK or not,” she said recently. “There’s a certain percent chance you’re going to be all right. But then, maybe you’re not.”

Patty and Victor Vurpillat are infected with a strain of human papilloma virus--HPV--the virus that lurks behind one of the country’s fastest-spreading sexually transmitted diseases and is rapidly becoming a prime suspect in the search for the causes of cervical cancer.

As much as 15% of the population may already be carrying the virus--a fact that many health officials view with alarm. It is estimated that 750,000 people become infected every year--most of them teen-agers and young adults who are healthy, sexually active and entering their peak reproductive years.

For most of them, HPV infection will mean nothing more than a frustrating struggle with the virus’s most common visible symptom, genital warts--small, cauliflower-like growths that usually can be removed with various disconcerting and less-than-perfect treatments.

But, for a few, HPV may contribute to a profoundly disturbing form of cancer--cancer of the genitals, and in particular, cervical cancer, a condition that threatens the core of one’s sexuality, the ability to reproduce and, occasionally, life itself.

The difficulty is, it is impossible to predict who will fall into which group.

As a result, millions of Americans find themselves condemned to a sentence of life beneath the cloud of HPV, carrying in their tissues an incurable and highly infectious virus that may eventually unleash a devastating cancer.

The burden falls especially hard on women. Both sexes can carry and spread the virus, but symptoms are more pronounced in women. Although the virus has been associated with cancers of the penis and anus, the greater risk appears to be cancer of the cervix.

What’s more, some people are spreading the virus unknowingly: It is transmitted by contact with warts, and warts often go unnoticed. Some physicians suspect that HPV may even occasionally be spread indirectly--perhaps on a tanning bed, toilet or washcloth.

For that reason, it may not be possible to protect oneself completely. Physicians strongly recommend condoms. But they acknowledge that even condoms are not foolproof; some warts remain exposed, and contact can occur before or after the condom is used.

What are the long-term implications of the spread of such a virus?

Many researchers insist that HPV is unlikely to produce a significant increase in the number of deaths from invasive cervical cancer in the United States, because cervical cancer is highly treatable and, in most cases, even preventable if women are screened regularly.

Nevertheless, some have noticed a worrisome trend--an apparent rise in the incidence of cervical dysplasia, abnormalities in the cells on the surface of the cervix that, although treatable, in some cases turn out to be antecedents of cancer.

Some physicians also have reported an increase in adenocarcinomas, a particularly nasty subset of cervical tumors. Those tumors now seem to strike younger women in particular, researchers say; and they may be especially difficult to detect early and cure.

Both of those trends, which some researchers believe may be linked to HPV, suggest a startling shift in the demographics of cervical cancer: A disease that in the past has afflicted mostly women in their late 40s and beyond is now threatening women in their prime.

“My guess is that the teen-age cervix is phenomenally sensitive, in that there is a tremendous amount of cell division,” says Dr. Stephen L. Curry of Tufts University. “If they are exposed to whatever carcinogens there are, there will be a higher incidence of cancer.”

Even more troubling is the fact that as many as half of all women in the United States don’t undergo annual cervical cancer screening, without which it is impossible to detect and treat the cancer’s precursors, staving off more serious disease.

At a large public-health clinic near downtown Los Angeles that serves mostly low-income Latinos, women are turning up with the earliest stages of cervical cancer at twice the national rate, and their average age is just 24.

HPV infection is rampant among her clients, says Catherine Wylie, who oversees the family-planning program at the H. Claude Hudson Comprehensive Health Center at Adams Boulevard and South Grand Avenue. The spread will continue, she says, until the law requires that partners of people who have HPV be tracked down and treated.

“Our women have sex early because they marry at 16 to 18,” Wylie said recently. “As long as this disease is not reportable, and there’s no partner follow-up and treatment, I think we’re going to have an epidemic of cervical cancer.”

THERE IS NOTHING new about warts--on the genitals or elsewhere. They have been around for millennia. As early as the 1st Century AD, physicians described the more ignominious form--warts on the genitals and anus, also known as condylomata.

But it was not known until this century that warts came from viruses--a specific family of viruses called human papilloma viruses. (It is now known that some strains cause common warts on the hands and feet and other strains cause genital warts.)

That discovery led next to an intriguing glimpse of HPV’s mysterious links to cancer.

In the early 1930s, researchers discovered that a form of papilloma virus caused benign tumors (also known as papillomas) in cottontail rabbits. When exposed to certain chemicals that were otherwise innocuous, those tumors quickly turned malignant.

Even today, those initial animal experiments remain a model for examining the way papilloma virus-induced abnormalities can progress to cancer, researchers say. But the links between HPV and human cancers would remain unrecognized for another 40 years.

In the meantime, it became clear how HPV is spread.

The first report of sexual transmission of HPV came in 1954. Twenty-four women came down with genital warts after their husbands returned from the Far East. All 24 husbands admitted to having had sex overseas, and all had recently had penile warts.

Sex with a partner who has untreated warts is known now to be extremely risky, since the virus is highly concentrated in warts. In studies, most partners of people with warts developed warts themselves within weeks or months. Cuts and abrasions appear to increase one’s infection with the virus.

There is at least one other form of transmission: HPV can be spread to an infant during childbirth. In rare cases, the infection produces a life-threatening condition in which warts on the infant’s larynx interfere with his or her ability to breathe.

And because physicians have seen instances of HPV spreading in cases in which no sexual contact is believed to have occurred--for instance, among non-intimate members of the same household--some wonder whether HPV is spread in other ways. Those cases, however, are difficult to prove.

By whatever routes, genital warts began proliferating in the 1960s under the influence of increased sexual freedom and declining use of barrier contraceptives. Statistics on visits to U.S. physicians indicate a 12-fold increase in cases in just 20 years.

According to the National Disease and Therapeutic Index, the number of visits for treatment of genital warts leaped from 160,000 in 1966 to 1 million just a decade later. By 1988, that number had reached 1.2 million. In the meantime, HPV research languished, in part because of an obstacle that has yet to be overcome. Scientists had never managed to grow HPV in the laboratory, making it difficult to study its transmission, its treatment and how the virus affects cells.

Then in the mid-1970s, a pathologist working in a laboratory in Canada began noticing a peculiar pattern under his microscope: He found striking similarities between cells from genital warts and cells from pre-malignant lesions on the cervix.

The pathologist, Alexander Meisels, a professor at Quebec’s LaVal University, was intrigued by two features in particular. The cells he was studying seemed to have in common an unusual cavity around the nucleus and an overabundance of a protein called keratin.

Suddenly, it dawned on Meisels: The lesions must have come from the same source as the warts. If HPV caused not just warts but cervical lesions as well, and lesions were known in some cases to develop into cancer, then HPV had a role in the process leading to cervical cancer.

“The cells seem to have to be infected (with HPV) first,” says Meisels, who is also head of the department of pathology and cytology at Saint-Sacrement Hospital. “But that is not sufficient. Something else is acting on them.”

Cervical cancer has long been thought to be caused at least in part by a sexually transmitted infectious agent. Among the most important risk factors for the disease is simply the number of sexual partners a woman has had and the number of partners her partner has had.

Worldwide, cervical cancer is a top cancer killer. Half a million women come down with it annually. Half of those women will die within 2 1/2 years, mostly in countries with poor access to health care and inadequate cervical cancer screening.

In the United States, the death rate has plummeted since the Papanicolaou smear made it possible to identify and treat the precursors of cervical cancer. This year, there will be about 13,500 new cases of invasive cancer and 6,000 deaths--down nearly 70% since the 1950s.

Even so, some researchers are worried by recent reports of an increase in the especially virulent adenocarcinomas--an apparent rise that some believe may come from a sexually transmitted infectious agent, perhaps HPV.

Twenty years ago, this particularly aggressive type of tumor made up just 5% of all invasive cervical cancers. Now that figure is 30%, says Dr. Alex Ferenczy, a professor of pathology and obstetrics and gynecology at McGill University in Montreal.

There are also signs that invasive cancer is striking at a younger age. According to Ferenczy, 22% of all invasive cancers in developed countries are now diagnosed in women aged 35 and younger. That figure is up from less than 10% just 15 years ago.

“That’s a heavy-duty increase,” Ferenczy says. “This has major clinical implications for whoever screens women for cervical cancers. They have to remember that invasive cancer is no longer and not necessarily a disease for elderly women.”

THAT LESSON is not lost on Dr. Louise H. Connolly, medical director of the Manhattan Beach Women’s Health Center, a full-service medical clinic operated by Centinela Hospital on a busy South Bay thoroughfare a few miles from the beach.

A graduate of Yale Medical School, Connolly opted for a career in obstetrics and gynecology. What appealed to her was the possibility of practicing preventive medicine--as she puts it, protecting a woman’s right to sexuality without harmful consequences.

But these days, harmful consequences walk into the office every day. About one in five of Connolly’s patients is infected with HPV. The average age of those women, Connolly figures, is 22. News of the diagnosis, and the risk of cancer, comes as a rude shock.

“When you’re 18 to 25, you feel that your health is guaranteed. You feel invulnerable to major disease,” Connolly says. “I think initially they’re shocked and frightened that they’re 18 or 20 years old and they have something that might lead to cancer.

“Right behind that, they feel they have a sexually transmitted disease and they may feel dirty,” she added. “So it’s fear and shame together. It cuts them off from asking people for support--from family, boyfriends and friends.”

One woman, who asked to be identified simply as Annie, was in her mid-40s when she discovered that she had genital warts. She was divorced at the time, sexually active and in a relationship with a man she has since married.

Annie had no gynecologist, so she told her family doctor. For a year and a half, they fought a losing battle against the warts. Annie would go in for treatment with various ointments, the warts would disappear, and within several months they would be back.

“It’s emotionally painful and it’s demeaning,” Annie says. “You’ve got a sexually transmitted disease and someone is fooling with your bottom. And to be honest, one of the hardest parts about the whole thing was my husband’s lack of understanding.

“He just didn’t understand what I was going through emotionally,” she says. “It was more like an imposition to him. He’d see me going for another treatment and he’d think, ‘She’s going to be out of commission for a week.’ ”

After eight or 10 episodes, even the physician was becoming impatient. So when the next wart arrived, Annie went to see Connolly. “When she examined me, she said, ‘This is not a wart,’ ” Annie recalls. “ ‘It’s something else, and I want to remove it.’ ”

Connolly cut off the growth and sent it in for a biopsy. The results came back: Annie had early cancer of the vulva. (Vulval cancer is another genital cancer that has been linked to HPV but is less common than cervical cancer.)

Fortunately, Annie’s cancer was at its earliest stage. It was confined to the top layer of the skin and could be cut off easily. Simply removing it and a surrounding margin of normal tissue for a pathologist’s scrutiny would probably be sufficient treatment.

But Connolly had Annie return for colposcopy, an extensive internal examination with a binocular microscope that magnifies and illuminates the vagina and cervix. Through the scope, Connolly would be able to detect any warts or more troubling changes.

“It was horrible, just horrible,” Annie remembers, referring to her fear of what Connolly might find. “There you are, spread-eagle, for (nearly half) an hour. None of it really hurts. . . . But every time she’d stop and look at something, I’d think, ‘Oh God, oh God, oh God.’ ”

HPV infection contributes to a range of manifestations in women. They fall along a continuum from barely significant to severe. Some people suffer no symptoms, some suffer just one. Others proceed at varying rates of speed from one to the next.

The least serious are warts and so-called subclinical infections--barely perceptible changes in the cells that cover the cervix. A specialist scrutinizing cells scraped off during a Pap smear might detect the virus’s distinctive footprint--clumps of oddly misshapen cells.

More-extensive cell changes create a condition known as dysplasia, or cervical intraepithelial neoplasia (CIN). Those abnormalities can be detected through Pap smears or colposcopy, where they appear as areas of white tissue where it should be smooth and pink.

Dysplasia can range from mild to severe. Many cases will clear up spontaneously, some become worse. A small minority seem to advance to become carcinoma in situ , an early and highly treatable form of cancer confined to the top layer of tissue of the affected organ.

Finally, there can be invasive, or malignant, cancer.

Deep in the vastness of Los Angeles County USC Medical Center, Carol Carriere peers through a microscope at a small glass slide. Thousands of cells from a woman’s cervix are smeared on the slide, clustered like dense constellations of stars.

Carriere is chief cytotechnologist in the Department of Cytology at County USC. Some 30,000 slides pass through her lab every year. Most are from Pap smears, and many carry the tell-tale signs that HPV has invaded the cells.

Scanning the slide, Carriere looks for subtle changes--say, a cell with an oversized nucleus or cells in abnormal patterns of clumping. A key tip-off to HPV’s presence is that enlarged and irregularly shaped nucleus, often surrounded by a widening cavity.

In moderation, she says, those changes suggest subclinical infection or warts. More extensive abnormalities may indicate pre-malignant cells.

Treatment of HPV-related diseases depends upon the symptoms. There are no drugs that can rid the body of the virus, just as there is no vaccine. So physicians such as Connolly treat the manifestations: They freeze or vaporize or slice off the warts and areas with abnormal cells.

The first line of attack is a variety of chemicals, administered either by the patient or physician. For persistent warts and warts on the cervix, many physicians use cryosurgery, freezing the wart and surrounding tissue with a low-temperature probe.

Another option for extensive warts and dysplasia is laser surgery, in which a concentrated beam of light serves as a scalpel. Finally, a so-called cone biopsy is occasionally used to slice a cone-shaped chunk of abnormal tissue from the cervix.

It is not really known why such approaches work, but they seem to. Many people treated for warts and dysplasia never experience a recurrence. By removing a repository of virus, the treatments may be diminishing the load of virus in the body. Or, they may be triggering an immune response.

Nevertheless, there are limitations.

“It’s clear that you can’t cure a viral infection by burning the skin off,” says Dr. Kenneth L. Noller, chairman of the department of obstetrics and gynecology at the University of Massachusetts Medical School. “It would be like trying to cure a cold by burning off the lining of the lungs.”

Connolly, for one, also prescribes what she discreetly terms “pelvic rest” until the warts or areas of dysplasia have been treated and have healed. She advises frequent Pap smears--as often as every three to six months--a repeat colposcopy in a year and examination and treatment of any partners.

“Most of them drag their feet,” Connolly says. “Some couples break up: She gets angry, they have a fight, he leaves.”

Genital warts are common in men as well as women. They can occur on the penis, anus, scrotum and in the urethra. But they are often less visible than on women, noticeable only with close examination. So, many men unknowingly infect their partners.

There may also be certain “high-risk males”--men for whom a succession of partners or wives develop cervical cancer. Some researchers have speculated that such men are transmitting some carcinogen, probably an infectious agent, perhaps a strain of HPV.

Gynecologists say many men’s physicians are unfamiliar with HPV infection.

“Some of them will just go to their family practitioner, who just eyeballs them and says, ‘No, you don’t have it,’ ” says Dr. Virginia A. Siegfried of Los Angeles. “That may be part of the problem in some of the patients we seem to keep getting back again: They’re just re-exposed.”

“You need a urologist or dermatologist who will go over the entire penis, urethra, scrotum and peri-anal area carefully,” Connolly says. “They should check the opening of the urethra to make sure there isn’t one tiny wart sitting in there that’s going to infect someone.”

Nan Singer (not her real name) discovered in her early 30s that her husband had warts on his anus. When she asked him about them, he conceded that he had had them for seven months. But he had neglected to tell her, and had neglected to have them treated.

Even after she confronted him, her husband was reluctant to see a doctor. Then he expected Nan to be responsible for seeing that he used the medication, and even for administering it. Nan felt betrayed and disgusted; their sexual relationship deteriorated. Existing problems in their marriage grew worse.

“The thing that shocked me was that he was so uninformed,” says Nan, who believes her husband’s response to the disease contributed significantly to their subsequent divorce. “He knew what they were, but he made no effort to understand what it could mean to me.”

Nan began having Pap smears every four to six months. One after another, they came back normal, or Class 1. Then, during one four-month period, the results switched suddenly from Class 1 to Class 3, signifying cell changes consistent with dysplasia.

Nan’s gynecologist recommended laser surgery, a process Nan likens to “taking napalm to your insides.” She describes her recovery as protracted and painful, sloughing off dead tissue for days. The smell seemed so foul, she feared co-workers noticed.

Neither Nan nor Annie has had any further problems. But both are familiar with their gynecologists’ waiting rooms. They go in every few months and have tried to make peace with the unsettling knowledge that trouble could surface any time.

Nan has become one of those women Connolly set out to protect: She is now a veteran of HPV, herpes infection, three ectopic pregnancies and pelvic inflammatory disease; but at 34, she remains determined to preserve her ability one day to conceive and bear a child.

“I’ve lived with a lot of pain and this bad equipment for years,” Nan said bitterly one morning recently, in an interview at her home near Los Angeles. “I (am not) about to lose it for venereal warts.”

UNFORTUNATELY, THERE are as many questions as there are answers about HPV.

Many more people are infected than come down with any visible symptoms. What percentage will develop symptoms remains unknown. “People are flipping up figures,” Ferenczy says. “Probably 5% to 15% will show up with some sort of HPV-related disease.”

Of those who do, most will develop warts or dysplasia. In many of those, the conditions might clear spontaneously if left alone. In a small percentage, HPV infection will lead to cancer. What percentage that will be, and who they are, is impossible to say.

“I’m not sure now we know what the true risk is to a woman who has HPV infection,” says Dr. John Curtin, a gynecologic oncologist at the USC School of Medicine.

The infection can remain hidden for long periods, surfacing at any time. One 65-year-old woman in Minnesota recently developed genital warts inexplicably, leaving her physician, Dr. Leo B. Twiggs, wondering why her symptoms emerged when they did.

According to Twiggs, director of the Women’s Cancer Center at the University of Minnesota Hospital, research suggests that symptoms may surface when a patient’s immunity is down. Other factors probably cause the immune suppression, he says; but maybe the virus can, too.

“Once the virus is interlocked into the cells, it’s like a small computer program or a mini-computer hooking into a mainframe,” Twiggs says. “The question is, where does it sit? Next to what operations systems? What’s it doing there?” No one really knows what turns the program on.

Another question is one foreshadowed a half-century ago in the initial experiments with papilloma virus infection in rabbits: What are the so-called co-factors that encourage the progression to cancer? Are there ways women can minimize their risk?

One prime suspected co-factor is cigarette smoking. Opinion is divided on oral contraceptives. Other possible co-factors include additional infectious agents, such as the herpes virus, hormonal influences, genetic background and environmental and dietary factors.

The National Cancer Institute is preparing to try to answer the co-factor and risk questions with the help of a study of 15,000 to 20,000 women. Researchers will track them for several years to determine who among them develops the kinds of abnormalities known to precede cervical cancer.

They will then screen the women for HPV infection and those possible co-factors that might have played a role in their symptoms. Thus, researchers hope to be better able to predict the consequences of HPV infection and what puts people at greatest risk.

“What’s certain is if you have an abnormal Pap smear or dysplasia, you are more likely to have the virus detected,” says Dr. Mark Schiffman of the National Cancer Institute. “But if you have HPV today but are normal, does that mean you will get an abnormal smear?

“People assume that women with the virus will go on and get dysplasia,” Schiffman says. “Maybe the answer is no. Maybe most women can fight off the virus with their immune system. . . . We are trying to determine for physicians and women the meaning of infection.”

It is also possible that, in some women, warts and mild dysplasia will disappear without treatment. For that reason, there is disagreement among physicians about when treatment is warranted and how much difference it makes.

Dr. Jonathan S. Berek, director of gynecologic oncology at the UCLA School of Medicine, believes that some women are being over-treated--at considerable pain and expense and with limited evidence that the therapy really helps.

But other physicians argue that they cannot afford to wait. If even a small minority of patients risk developing cancer, they suggest that it would be irresponsible to not do everything possible to protect those patients.

“Since we don’t have the tools to say which will progress . . . you’re almost forced to over-treat the others,” Connolly says. Furthermore, many patients are anxious to be rid of their warts.

There is similar controversy about the value of a new form of HPV testing.

There are now some 60 known strains of the virus. (In 1987, they were being identified at a rate of three a month.) Some are found primarily in benign warts; some turn up in connection with dysplasia. A few seem to be linked primarily to invasive cancers.

But the associations are not hard and fast.

Several companies have developed tests capable of identifying the strain with which a person is infected. The first test on the market appeared in the United States early last year and is being offered by some commercial labs.

The manufacturer suggests that the test be used with the Pap smear to alert physicians to the presence of a potentially cancer-causing virus. The company claims that once physicians know the strains involved, they can monitor their patients accordingly.

But some physicians counter that all patients should be closely monitored anyway. They say the association between specific strains and symptoms is not yet sufficiently clear to justify alarming, or reassuring, patients on the basis of the test.

“I’m not sure how to use it, to tell you the truth,” says Siegfried of Los Angeles. “It doesn’t change how we treat the patients, and I’m concerned that it might cause more anxiety if the patients are told they have the type that is more closely linked to cancer.”

IN THE END, researchers say that panic about HPV is counterproductive.

Most people never will develop cervical cancer, they repeatedly point out. The disease’s antecedents are easily detected and treated. And in most cases, the rate of progression is slow enough that a single missed Pap smear will not be crucial.

But with nearly half the women in the United States not undergoing regular screenings, says Berek of UCLA, attention should be focused on encouraging those women to change their lifestyles and get regular checkups.

Berek would like to see more public resources devoted to comprehensive cancer screening of all Americans--an approach he and others point out repeatedly has been proven cost-effective but rarely attracts much political support.

“So I think the broader issue here is not so much that we’ve identified a virus that causes warts--a small proportion of which are virulent and probably are associated with the development of genital cancers,” Berek says. “The issue is who’s getting screened and why can’t we save those other 6,000 lives?”

But statistics offer little comfort to people such as Patty Vurpillat.

In Patty’s case, the warts on her cervix returned within a few months of treatment. When the clinic advised a second biopsy, she balked. She feared the pain of another biopsy and was losing confidence in the clinic where she was being treated.

Unsatisfied and anxious, she sought a second opinion. In December, the new physician suggested waiting three months. Warts sometimes regress. If they don’t go away, the physician said, she might try once more freezing them off.

So these days, Patty Vurpillat is waiting.

“I’ve been worried,” she said sadly one recent afternoon. “It’s always in the back of your mind: I’m thinking, ‘Could something really be messing up my reproductive system?’ I’m going to turn 20 this week. And I feel like I’m going to turn 40.”