The theme underlies much of the novel's subject: teens dying of cancer for no justifiable reason. As Hazel and Van Houten both say at times, cancer is just a side effect of an evolutionary process. It isn't personal. It has no agenda, no feeling toward the person it's killing. This indifference is the reason Augustus finds no heroism in dying of it. It's just trying to be alive itself, and in fact it isn't some separate parasite: it's made of his own cells. That complete insensitivity is something Hazel also struggles with. After Augustus dies, she thinks of her father's earlier comment that the universe just wants to be noticed, and she reverses the phrase, saying what we want is to be noticed by the universe. The problem, as she puts it, is “the depraved meaninglessness of these things.” What her thought suggests is that some of things that happen to people, like developing cancer, occur at random, not with any maliciousness intended, but neither with any purpose. We want the universe to notice us, but it simply isn't aware. The title of the novel speaks to this idea. It comes from Shakespeare's “The Tragedy of Julius Caesar,” in which Cassius says, “Men at some times are masters of their fates: / The fault, dear Brutus, is not in our stars / But in ourselves.” The word stars here refers to fate. Hazel applies these lines to her own situation and concludes the opposite: the fault for their dying of cancer is not their doing but fate's.
The Fault in Our Stars takes joy in poking fun at clichés and baseless social conventions, especially regarding cancer kids and coming to terms with death. The novel seeks to downplay the popular idea that battling cancer is a noble, heroic, and rewarding act, and it does so primarily by showing the realities of cancer. There is nothing particularly noble for Hazel about struggling to breathe and knowing her death will hurt others, or anything heroic for Augustus in having had a leg amputated, or rewarding for Isaac about losing his vision. Instead the reader sees that kids with cancer are just that: kids. What makes them different from other kids is that they're put in the terrible position of having to deal with a debilitating and sometimes fatal illness. Augustus discusses this idea directly when he tells Hazel about his former girlfriend, Caroline Mathers. He talks about the trope of the cancer victim who heroically fights cancer until the end, then points out that kids with cancer aren't statistically anymore likely to be better people than kids without cancer. Caroline, he explains, became increasingly cruel toward him as her condition worsened. Rather than make her a better person, cancer made her worse.
The most poignant example of cancer's reality is Augustus himself after his cancer reappears. He withers quickly, and Hazel witnesses all the humiliation and pain he suffers as a result. He loses control of his body, urinates in his bed, and becomes confined to a wheelchair. When he calls her for help after driving to the gas station, she thinks of the person he's become, noting that the “Augustus Waters of the crooked smiles and unsmoked cigarettes was gone, replaced by this desperate humiliated creature sitting there beneath me.” A few lines later, she thinks of the conventions of the cancer kid, how they're supposed to maintain their humor and spirit through to the end. But Gus was the reality: suffering, frightened, and pitiful while struggling not to be. Through these details, the novel shows that the the false and feel-good conventions regarding cancer kids are really just hollow clichés used by society to deal with an uncomfortable subject.
The Author's Note refers to the idea that “made-up stories can matter” as “sort of the foundational assumption of our species,” and from that point forward the value of fiction is a prominent theme throughout The Fault In Our Stars. It turns up most prominently in Hazel's relationship with her favorite book, An Imperial Affliction. Hazel describes the book as her personal bible, as it's the only account she's read of dying from cancer that accurately matches her own experience. It offers her a sort of companionship, which comforts her. The question of whether or not fictional characters and a made-up story can have genuine value in a real person's life comes up when Peter Van Houten, the author of An Imperial Affliction, responds to one of Augustus's emails. Augustus told Van Houten the book meant something to him, to which Van Houten replies by wondering what value fiction really has. He suggests that it may offer the temporary illusion that life has meaning, when in fact it may not. He also wonders if fiction should act more like a call to arms, alerting people to things they should pay attention to, or a morphine drip, numbing them. But the Author's Note of The Fault In Our Stars offers John Green's answer, at least, to whether or not fiction has value. He believes it does, and the comfort, joy, and companionship Hazel finds from An Imperial Affliction in the novel similarly implies that made-up stories can be truly important.