Viral fingerprints: Sharmila Sengupta (right) and a co-researcher at the ISI lab (Picture by Sanat K. Sinha)

The classical medical teaching was that it is a disease of ‘bad girls’. But then doctors gradually realised that not just the promiscous, it can affect any sexually active woman. By the middle of the 1960s, cancer specialists knew that at least one out of seven women in the US and Europe gets this cancer primarily spread by a killer microbe called human papilloma virus (HPV). And Indian oncologists discovered that the type of cancer kills at least 74,000 women in the country every year.

One of the most neglected diseases among women in India, cervical cancer ravages the inner lining of the cervix ? the neck of the womb. Though this cancer was long recognised as a sexually transmitted disease, not until the 1990s was HPV identified as the likely culprit. In the years since, medical researchers have slowly unravelled the complex relationship between this virus and the cancer it can cause.

“The cervical epithelium of almost 99.7 per cent of women affected with cervical cancer is infected with HPV,” says Dr Sharmila Sengupta, assistant professor at the Human Genetics Unit, Indian Statistical Institute (ISI), Calcutta, who has been working on the cancer for the last eight years.

Of the 100 types of HPV identified all over the world, 15 cause cervical cancer. These are high-risk types, or oncogenic. “Two of them, HPV 16 and 18, together account for a majority of cervical cancers,” says Sengupta.

However, becoming infected with an oncogenic virus only rarely results in cancer. “Even when it does, a very long time elapses between the initial infection and the development of malignancy, making it possible for doctors to intercept and prevent cancer,” explains Sengupta. Also, there are low-risk HPVs that more often cause genital warts; they rarely, if ever, result in cancer.

Because, an overwhelming majority of sexually active women can expect to be infected with one or another HPV, a routine examination of the vaginal smear is suggested to arrest the disease in an early stage when it’s possible to remove the lesions before they turn malignant.

“However, in a country like India with strong cultural and religious taboos, women show little interest in getting pap tests,” says Dr B.C. Das, director, Institute of Cytology and Preventive Oncology, Noida. “While routine screening tests have helped bring down the incidence of cervical cancer in Western countries, it hasn’t been possible in India.” Besides, pap test, though still considered the cheapest and the most effective method, is quite crude and inexact.

With a pap smear, someone has to inspect every cell on the slide: if the sample includes only a few abnormal cells in a dense background of healthy ones, they can be easily missed, particularly by inefficient or overworked pathologists. One way to improve on pap diagnosis is to include DNA testing of papilloma virus. But then it will be too expensive to afford for people in countries like India.

“To cut down the huge disease burden what we immediately need is a vaccine to combat HPV,” says Das. But finding out an ideal vaccine for India won’t be an easy task. Although two new vaccines are in the final stages of testing in different parts of the world, experts in India are not sure whether they’ll be of any help here. One of the vaccines protects against the two HPV types, 16 and 18, that are most often involved in cancer. The other protects against these two and two others, HPV 6 and 11.

“The problem with HPV is that even within the major two types, there are subtypes with geographically variable frequencies,” says Sengupta. “Besides, there are co-factors related to the specific host (the infected person) and environment.” In other words, stereotypes don’t apply for HPV or cervical cancer. For instance, in course of their study on the Muslim women in West Bengal, the ISI group found that the much-acclaimed fact that Muslim women are less susceptible to HPV-related cervical cancer, because their male partners are circumcised, is a myth. “In addition, we have also found that genetic variations between individuals in immune-related genes may influence response to HPV infections, including those that transform normal cells into cancerous ones,” she adds. A recent study by the group, published in Gynecologic Oncology, has found that HPV 16 (the more prevalent type in India) significantly varies in genetic structure in India compared to the type found in Europe. “Both the virus and the host have undergone evolution over time and six different HPV 16 lineages have been found.”

Such huge genetic variations of HPV naturally raises a question: will the new vaccines, primarily meant to combat European subtypes, work in India? “We are going to begin a trial with one of the new vaccines to find out if it is effective in India,” said Das.

“Even if the vaccine works, it will be of little use to India because it’s a prophylactic (preventive) one,” says Sudhir Krishna, a senior faculty at the National Centre for Biological Sciences (NCBS), Bangalore, who has been co-ordinating research on HPV across India. “Which means you give them to women who are not infected by HPV.” He thinks India needs a therapeutic vaccine capable of working on women already infected with the virus and going through a precancerous stage. “Women consult doctors when they are already infected and the disease is either in an early or an advanced stage,” says Krishna.